The preparation and readiness for voluntary movement: a high-field event-related fMRI study of the Bereitschafts-BOLD response

Activity within motor areas of the cortex begins to increase 1 to 2 s prior to voluntary self-initiated movement (termed the Bereitschaftspotential or readiness potential). There has been much speculation and debate over the precise source of this early premovement activity as it is important for understanding the roles of higher order motor areas in the preparation and readiness for voluntary movement. In this study, we use high-field (3-T) event-related fMRI with high temporal sampling (partial brain volumes every 250 ms) to specifically examine hemodynamic response time courses during the preparation, readiness, and execution of purely self-initiated voluntary movement. Five right-handed healthy volunteers performed a rapid sequential finger-to-thumb movement performed at self-determined times (12-15 trials). Functional images for each trial were temporally aligned and the averaged time series for each subject was iteratively correlated with a canonical hemodynamic response function progressively shifted in time. This analysis method identified areas of activation without constraining hemodynamic response timing. All subjects showed activation within frontal mesial areas, including supplementary motor area (SMA) and cingulate motor areas, as well as activation in left primary sensorimotor areas. The time courses of hemodynamic responses showed a great deal of variability in shape and timing between subjects; however, four subjects clearly showed earlier relative hemodynamic responses within SMA/cingulate motor areas compared with left primary motor areas. These results provide further evidence that the SMA and cingulate motor areas are major contributors to early stage premovement activity and play an important role in the preparation and readiness for voluntary movement. (C) 2003 Elsevier Inc. All rights reserved.

Simultaneous X-ray imaging of plant root growth and water uptake in thin-slab systems

Direct and simultaneous observation of root growth and plant water uptake is difficult because soils are opaque. X-ray imaging techniques such as projection radiography or Computer Tomography (CT) offer a partial alternative to such limitations. Nevertheless, there is a trade-off between resolution, large field-of-view and 3-dimensionality: With the current state of the technology, it is possible to have any two. In this study, we used X-ray transmission through thin-slab systems to monitor transient saturation fields that develop around roots as plants grow. Although restricted to 2-dimensions, this approach offers a large field-of-view together with high spatial and dynamic resolutions. To illustrate the potential of this technology, we grew peas in 1 cm thick containers filled with soil and imaged them at regular intervals. The dynamics of both the root growth and the water content field that developed around the roots could be conveniently monitored. Compared to other techniques such as X-ray CT, our system is relatively inexpensive and easy to implement. It can potentially be applied to study many agronomic problems, such as issues related to the impact of soil constraints (physical, chemical or biological) on root development.

A methodology for current density calculations in high-frequency RF resonators

As nuclear magnetic resonance imaging and spectroscopy move inexorably toward higher field-strength magnets in search of improved signal-to-noise ratio, spectral resolution, and spatial resolution, the way in which radiofrequency (RF) probes are designed changes. At higher frequencies, resonant cavities become the favored RF ''coil'' type and may be built using streamline elements to reduce the inductance of the system. In modeling such systems, the quasi-static approach of assuming that current flows evenly in all conductor cross sections and that adjacent conductors do not affect each other becomes less reasonable. The proximity of RF conductors in resonators typically causes RF eddy currents to flow, whereby the current density in each rung is altered by the RF fields generated by nearby conductors. The proper understanding and prediction of how resonators will perform require a model of the current densities flowing in conducting sections, including all RF eddy current effects. Very few models of this type have been presented in the literature. This article presents an overview of one such model and of how it may be applied to a variety of resonators, both shielded and unshielded, circular, and elliptical, in cross section. Results are presented from a shielded head coil operating at 2 tesla. (C) 1997 John Wiley & Sons, Inc.

Nmr imaging of the diffusion of water into poly(tetrahydrofurfuryl methacrylate-co-hydroxyethyl methacrylate)

0Nuclear magnetic resonance (n.m.r.) imaging was used to study the ingress of water into poly(tetrahydrofurfuryl methacrylate-co-hydroxyethyl methacrylate). The study offers strong evidence that the diffusion is Fickian in nature. The diffusion coefficient, D, obtained by fitting the underlying diffusion profile, attainable from the images, according to the equation for Fickian diffusion, is 1.5 x 10(-11) m(2) s(-1), which is in good correlation with the value of 2.1 x 10(-11) m(2) s(-1), obtained from mass uptake measurements. Additionally, from the T-2-weighted images, Superimposed features observed in addition to the underlying Fickian diffusion profiles were shown to have a longer spin-spin relaxation time, T-2. This Suggests the presence of two types of water within the polymer matrix; a less mobile phase of absorbed water that is interacting strongly with the polymer matrix and a more mobile phase of absorbed water residing within the cracks observed in the environmental scanning electron micrograph. (C) 1997 Elsevier Science Ltd.

A high-resolution genetic map of the familial Mediterranean fever candidate region allows identification of haplotype-sharing among ethnic groups

Familial Mediterranean fever (FMF) is a recessive disorder of inflammation caused by mutations in a gene (designated MEFV) on chromosome 16p13.3, We have recently constructed a 1-Mb cosmid contig that includes the FMF critical region. Here we show genotype data for 12 markers from our physical map, including 5 newly identified microsatellites, in FMF families. Intrafamilial recombinations placed MEFV in the similar to 285 kb between D16S468/D16S3070 and D16S3376. We observed significant linkage disequilibrium in the North African Jewish population, and historical recombinants in the founder haplotype placed MEFV between D16S3082 and D16S3373 (similar to 200 kb). In smaller panels of Iraqi Jewish, Arab, and Armenian families, there were significant allelic associations only for D16S3370 and D16S2617 among the Armenians. A sizable minority of Iraqi Jewish and Armenian carrier chromosomes appeared to be derived from the North African Jewish ancestral haplotype. We observed a unique FMF haplotype common to Iraqi Jews, Arabs, and Armenians and two other haplotypes restricted to either the Iraqi Jewish or the Armenian population. These data support the view that a few major mutations account for a large percentage of the cases of FMF and suggest that same of these mutations arose before the affected Middle Eastern populations diverged from one another. (C) 1997 Academic Press.

Screening Anal Dysplasia in HIV-Infected Patients: Is There an Agreement Between Anal Pap Smear and High-Resolution Anoscopy-Guided Biopsy?

PURPOSE: The purpose of this study was to analyze the agreement between anal Pap smear and high-resolution anoscopy-guided biopsy in diagnosing anal dysplasia in HIV-infected patients. METHODS: We conducted cross-sectional analysis of HIV-infected patients receiving anal dysplasia screening as part of routine care. Agreement between measures was estimated by weighted kappa statistics, using a three-tiered cytologic and histologic grading system (normal, low-grade dysplasia, and high-grade dysplasia). Estimates of sensitivity, specificity, and predictive values were calculated using a two-tiered cytologic and histologic grading system (""without dysplasia"" and ""with dysplasia of any grade""). Estimates were also calculated for the detection of high-grade dysplasia. RESULTS: During a one-year period, 222 patients underwent 330 anal Pap smears followed by high-resolution anoscopy-guided biopsies. There were 311 satisfactory Pap smears with concurrent biopsies. Considering histology the standard, the frequency of anal dysplasia was 46%. Kappa agreement between anal Pap smear and biopsy was 0.20. For detection of anal dysplasia of any grade, anal Pap smear showed sensitivity of 61%, specificity of 60%, positive predictive value of 56%, and negative predictive value of 64%. For high-grade dysplasia, anal Pap smear showed sensitivity of 16% and specificity of 97%. CONCLUSION: Anal Pap smears alone were not sensitive enough to rule out anal dysplasia. We recommend that high-resolution anoscopy-guided biopsy be incorporated as a complementary screening test for anal dysplasia in high-risk patients. Following baseline high-resolution anoscopy, these individuals could be followed with serial anal cytology to dictate the need for future high-resolution anoscopy-guided biopsies.

High-Resolution Genomic Mapping Reveals Consistent Amplification of the Fibroblast Growth Factor Receptor Substrate 2 Gene in Well-Differentiated and Dedifferentiated Liposarcoma

Well-differentiated liposarcoma (WDLS) is one of the most common malignant mesenchymal tumors and dedifferentiated liposarcoma (DDLS) is a malignant tumor consisting of both WDLS and a transformed nonlipogenic sarcomatous component. Cytogenetically, WDLS is characterized by the presence of ring or giant rod chromosomes containing several amplified genes, including MDM2, TSPAN31 CDK4, and others mainly derived from chromosome bands 12q13-15. However, the 12q13-15 amplicon is large and discontinuous. The focus of this study was to identify novel critical genes that are consistently amplified in primary (nonrecurrent) WDLS and with potential relevance for future targeted therapy. Using a high-resolution (5.0 kb) ""single nucleotide polymorphism""/copy number variation microarray to screen the whole genome in a series of primary WDLS, two consistently amplified areas were found on chromosome 12: one region containing the MDM2 and CPM genes, and another region containing the FRS2 gene. Based on these findings, we further validated FRS2 amplification in both WDLS and DDLS. Fluorescence in situ hybridization confirmed FRS2 amplification in all WDLS and DDLS tested (n = 57). Real time PCR showed FRS2 mRNA transcriptional upregulation in WDLS (n = 19) and DDLS (n = 13) but not in lipoma (n = 5) and normal fat (n = 9). Immunoblotting revealed high expression levels of phospho-FRS2 at 1436 and slightly overexpression of total FRS2 protein in liposarcoma but not in normal fat or preadipocytes. Considering the critical role of FRS2 in mediating fibroblast growth factor receptor signaling, our findings indicate that FRS2 signaling should be further investigated as a potential therapeutic target for liposarcoma. (C) 2011 Wiley-Liss, Inc.

Analysis of Detergent-Insoluble and Whole Cell Lysate Fractions of Resting Neutrophils Using High-Resolution Mass Spectrometry

Neutrophilic granulocytes play a major role in the initiation and resolution of the inflammatory response, and demonstrate significant transcriptional and translational activity. Although much was known about neutrophils prior to the introduction of proteomics, the use of MS-based methodologies has provided an unprecedented tool to confirm and extend previous findings. In the present study, we performed a Gel-LC-MS/MS analysis of neutrophil detergent insoluble and whole cell lysate fractions of resting neutrophils. We achieved a set of identifications through the use of high-resolution mass spectrometry and validation of its data. We identified a total of 1249 proteins with a wide range of intensities from both detergent-insoluble and whole cell lysate fractions, allowing a mapping of proteins such as those involved in intracellular transport (Rab and Sec family proteins) and cell signaling (S100 proteins). These results represent the most comprehensive proteomic characterization of resting human neutrophils to date, and provide important information relevant for further studies of the immune system in health and disease. The methods applied here can be employed to help us understand how neutrophils respond to various physiologic and pathophysiologic conditions and could be extended to protein quantitation after cell activation.

Timing and duration of the last interglacial inferred from high resolution U-series chronology of stalagmite growth in Southern Hemisphere

High-precision Th-230-U-238 ages for a stalagmite from Newdegate Cave in southern Tasmania, Australia define a rare record of precipitation between 100 and 155 ka before the present. The fastest stalagmite growth occurred between 129.2 +/- 1.6 and 122.1 +/- 2.0 ka (similar to 61.5 mm/ka), coinciding with a time of prolific coral growth from Western Australia (128-122 ka). This is the first high-resolution continental record in the Southern Hemisphere that can be compared and correlated with the marine record. Such correlation shows that in southern Australia the onset of full interglacial sea level and the initiation of highest precipitation on land were synchronous. The stalagmite growth rate between 129.2 and 142.2 ka (similar to 5.9 mm/ka) was lower than that between 142.2 and 154.5 ka (similar to 18.7 mm/ka), implying drier conditions during the Penultimate Deglaciation, despite rising temperature and sea level. This asymmetrical precipitation pattern is caused by latitudinal movement of subtropical highs and an associated Westerly circulation, in response to a changing Equator-to-Pole temperature gradient. Both marine and continental records in Australia strongly suggest that the insolation maximum between 126 and 128 ka at 65 degreesN was directly responsible for the maintenance of full Last Interglacial conditions, although the triggers that initiated Penultimate Deglaciation (at similar to 142 ka) remain unsolved. (C) 2001 Elsevier Science B.V. All rights reserved.

Integrating high and moderate spatial resolution image data to estimate forest age structure

The collection of spatial information to quantify changes to the state and condition of the environment is a fundamental component of conservation or sustainable utilization of tropical and subtropical forests, Age is an important structural attribute of old-growth forests influencing biological diversity in Australia eucalypt forests. Aerial photograph interpretation has traditionally been used for mapping the age and structure of forest stands. However this method is subjective and is not able to accurately capture fine to landscape scale variation necessary for ecological studies. Identification and mapping of fine to landscape scale vegetative structural attributes will allow the compilation of information associated with Montreal Process indicators lb and ld, which seek to determine linkages between age structure and the diversity and abundance of forest fauna populations. This project integrated measurements of structural attributes derived from a canopy-height elevation model with results from a geometrical-optical/spectral mixture analysis model to map forest age structure at a landscape scale. The availability of multiple-scale data allows the transfer of high-resolution attributes to landscape scale monitoring. Multispectral image data were obtained from a DMSV (Digital Multi-Spectral Video) sensor over St Mary's State Forest in Southeast Queensland, Australia. Local scene variance levels for different forest tapes calculated from the DMSV data were used to optimize the tree density and canopy size output in a geometric-optical model applied to a Landsat Thematic Mapper (TU) data set. Airborne laser scanner data obtained over the project area were used to calibrate a digital filter to extract tree heights from a digital elevation model that was derived from scanned colour stereopairs. The modelled estimates of tree height, crown size, and tree density were used to produce a decision-tree classification of forest successional stage at a landscape scale. The results obtained (72% accuracy), were limited in validation, but demonstrate potential for using the multi-scale methodology to provide spatial information for forestry policy objectives (ie., monitoring forest age structure).

Are pioneer axons guided by regulatory gene expression domains in the zebrafish forebrain? High-resolution analysis of the patterning of the zebrafish brain during axon tract formation

Although the principles of axon growth are well understood in vitro the mechanisms guiding axons in vivo are less clear. It has been postulated that growing axons in the vertebrate brain follow borders of neuroepithelial cells expressing specific regulatory genes. In the present study we reexamined this hypothesis by analysing the earliest growing axons in the forebrain of embryonic zebrafish. Confocal laser scanning microscopy was used to determine the spatiotemporal relationship between growing axons and the expression pattern of eight regulatory genes in zebrafish brain. Pioneer axons project either longitudinally or dorsoventrally to establish a scaffold of axon tracts during this developmental period. Each of the regulatory genes was expressed in stereotypical domains and the borders of some were oriented along dorsoventral and longitudinal planes. However, none of these borders clearly defined the trajectories of pioneer axons. In two cases axons coursed in proximity to the borders of shh and pax6, but only for a relatively short portion of their pathway. Only later growing axons were closely apposed to the borders of some gene expression domains. These results suggest that pioneer axons in the embryonic forebrain do not follow continuous pathways defined by the borders of regulatory gene expression domains, (C) 2000 Academic Press.

Exploring through cover - the integrated interpretation of high resolution aeromagnetic, airborne electromagnetic and ground gravity data from the Grant's Patch area, Eastern Goldfields Province, Archaean Yigarn Craton Part B; Gravity inversion as a

The cost and risk associated with mineral exploration in Australia increases significantly as companies move into deeper regolith-covered terrain. The ability to map the bedrock and the depth of weathering within an area has the potential to decrease this risk and increase the effectiveness of exploration programs. This paper is the second in a trilogy concerning the Grant's Patch area of the Eastern Goldfields. The recent development of the VPmg potential field inversion program in conjunction with the acquisition of high-resolution gravity data over an area with extensive drilling provided an opportunity to evaluate three-dimensional gravity inversion as a bedrock and regolith mapping tool. An apparent density model of the study area was constructed, with the ground represented as adjoining 200 m by 200 m vertical rectangular prisms. During inversion VPmg incrementally adjusted the density of each prism until the free-air gravity response of the model replicated the observed data. For the Grant's Patch study area, this image of the apparent density values proved easier to interpret than the Bouguer gravity image. A regolith layer was introduced into the model and realistic fresh-rock densities assigned to each basement prism according to its interpreted lithology. With the basement and regolith densities fixed, the VPmg inversion algorithm adjusted the depth to fresh basement until the misfit between the calculated and observed gravity response was minimised. The resulting geometry of the bedrock/regolith contact largely replicated the base of weathering indicated by drilling with predicted depth of weathering values from gravity inversion typically within 15% of those logged during RAB and RC drilling.

Structure of CcmG/DsbE at 1.14 angstrom resolution: High-fidelity reducing activity in an indiscriminately oxidizing environment

CcmG is unlike other periplasmic thioredoxin (TRX)like proteins in that it has a specific reducing activity in an oxidizing environment and a high fidelity of interaction. These two unusual properties are required for its role in c-type cytochrome maturation. The crystal structure of CcmG reveals a modified TRX fold with an unusually acidic active site and a groove formed from two inserts in the fold. Deletion of one of the groove-forming inserts disrupts c-type cytochrome formation. Two unique structural features of CcmG-an acidic active site and an adjacent groove-appear to be necessary to convert an indiscriminately binding scaffold, the TRX fold, into a highly specific redox protein.

Repeated three-dimensional magnetic resonance imaging of atherosclerosis development in innominate arteries of low-density lipoprotein receptor-knockout mice

Background-In vivo methods to evaluate the size and composition of atherosclerotic lesions in animal models of atherosclerosis would assist in the testing of antiatherosclerotic drugs. We have developed an MRI method of detecting atherosclerotic plaque in the major vessels at the base of the heart in low-density lipoprotein (LDL) receptor-knockout (LDLR-/-) mice on a high-fat diet. Methods and Results-Three-dimensional fast spin-echo magnetic resonance images were acquired at 7 T by use of cardiac and respiratory triggering, with approximate to140-mum isotropic resolution, over 30 minutes. Comparison of normal and fat-suppressed images from female LDLR-/- mice I week before and 8 and 12 weeks after the transfer to a high-fat diet allowed visualization and quantification of plaque development in the innominate artery in vivo. Plaque mean cross-sectional area was significantly greater at week 12 in the LDLR-/- mice (0.14+/-0.086 mm(2) [mean+/-SD]) than in wild-type control mice on a normal diet (0.017+/-0.031 mm(2), p