Areas Of Low Activity Research Articles

HIV, cyclophilins and nuclear entry: going under the radar

Lentiviruses such as HIV-1 traverse nuclear pore complexes (NPC) and infect terminally differentiated nondividing cells, but how they do this is unclear. Here we define a pathway involving direct interaction between HIV-1 capsid (CA) and cytoplasmicCyclophilinA (CypA), and the nuclear pore cyclophilin Nup358/ RanBP2. We show that these interactionsare essential for integration targeting and replication in primary human macrophages. In contrast to CypA Nup358 cyclophilin is insensitive to inhibition with cyclosporine. Inhibition of CypAusing cyclosporine or depletion of CypA levels by RNAi forces HIV-1 to enter the nucleus independently of Nup358 and the nuclear basket protein Nup153, suggesting that CypA regulates the choice of the nuclear import machinery that is engaged by the virus. Substitutions in capsid modulating CypA/Nup358 interactions switch integration into higher or lower gene density regions. HIV-1 cyclophilin-binding mutants CA G89V, P90A, or chimaeric HIV-1 containing SIVmac CA integrate in genomic areas of high gene density and activity, phenocopying integration of wild type virus in the presence of cyclosporine. In contrast, HIV-1 CA mutants that neither use Nup358 nor transportin 3 (CA N74D, N57A) integrate in genomic areas of low gene density and activity. Importantly, both groups of CA mutants are impaired in replication in HelLa cells and human monocyte derived macrophages. Our findings illustrate how HIV-1 engagescyclophilins to select a nuclear entry pathway required for integration into preferred genomic loci important for optimal proviral gene expression and replication and provide insight into lentiviral conservation of cyclophilin interactions.

Geothermal surface alteration of basalts, Krýsuvík Iceland—Alteration mineralogy, water chemistry and the effects of acid supply on the alteration process

The geothermal surface alteration of basalts and associated water chemistry at Krýsuvík, SW Iceland were studied. The geothermal area was characterised with zones of intensive surface alteration, steam vents, mud pots and hot springs. The steam-heated geothermal surface waters had pH values between 1.69 and 7.67 and total dissolved solid (TDS) concentrations between 154 and 6660 ppm, with Cl and SO 4 concentration decreasing and increasing with decreasing pH, respectively. Alteration mineral assemblages observed were strongly associated with the surface intensity. In areas of most intensive activity the basaltic rocks were altered to amorphous silica, anatase and pyrite with a crust of native sulphur at the surface. With decreased activity, kaolinite became important, as well as iron oxyhydroxides and oxides. On the flanks of the area montmorillonite was the predominant alteration product. Based on these observations the surface geothermal activity was divided into three groups: (1) high activity areas with active steam vents and mud pots and intensive acid leaching, (2) medium activity areas where the ground is hot, steam vents and mud pots are uncommon and the surface alteration is less intensive and (3) low activity areas on the margins of the surface geothermal activity. The primary factors influencing the steam-heated acid sulphate alteration of basalts included the redox state (oxidation front), supply of acids and pH, and the extent of reaction. The formation of iron- and sulphur-containing minerals and the respective elemental mobility depended on the redox conditions with pyrite formation under reduced conditions and goethite and/or hematite under oxidised conditions. At low pH, Ca, Mg, K and Na were mobile and leached out, whereas Fe, Ti and Al and to a large degree Si were retained in the alteration product. At higher pH values > 5 the mobility of Ca, Mg, K and Na was reduced due to the formation of clays.

An evaluation of the use of Telehealth within palliative care settings across Scotland

There is a lack of evidence-based research in the use of Telehealth within palliative care in the UK, particularly in Scotland. The aim of this project was to evaluate the current use of Telehealth applications within palliative care across Scotland, and how these and future applications are perceived by patients, carers and professionals. This paper reports on the qualitative findings from focus groups with patients and carers in three geographical areas in Scotland, and individual interviews with key stakeholders from across Scotland, who currently work within areas of high and low Telehealth activity. The key findings indicated that Telehealth initiatives are welcomed by patients and carers but that these should be an adjunct to clinical care rather than an alternative. The stakeholder interviews revealed several notable differences between those working within areas of high and low Telehealth activity. Principally, areas of high Telehealth activity appear to be driven by national and local policy and seem to benefit from a greater level of investment in Telehealth equipment and facilities than in the more central, and hence accessible, parts of Scotland.

High-performance and low platinum loading electrodeposited-Pt counter electrodes for dye-sensitized solar cells

This study demonstrates platinum (Pt) counter electrodes with low charge-transfer resistance (Rct), low Pt loading and high active surface area can be obtained within 30s by using the direct-current deposition in the presence of 3-(2-aminoethylamino)propyl-methyldimethoxysilane (Me-EDA-Si) as an additive. The addition of appropriate Me-EDA-Si can not only enhance the current efficiency but also inhibit the growth of semicircle-like grains, thus resulting in Pt electrode with high active surface area. Consequently, the dye-sensitized solar cells (DSSCs) fabricated with so-prepared Pt electrodes exhibited cell efficiency of 7.39% while 0.01vol% Me-EDA-Si was added, which is much superior to that with sputtered-Pt electrodes under the same assembly conditions.

The Velocity Characteristics of a Serial-Staged EHD Gas Pump in Air

The application of the ionic wind in the fields of aerodynamic control and heat transfer is limited by its low velocity and small active area. This paper deals with the experimental and theoretical analysis of the ionic-wind velocity in serial-staged electrohydrodynamic gas pumps under a negative corona discharge in air. Each stage consists of a pair of needle array-to-ring or needle array-to-mesh electrodes. It was observed that the active area of the gas pump can be enlarged by using a needle array electrode where the negative corona discharge started simultaneously and that the needle array-to-mesh electrode can generate a higher ionic wind velocity compared to that of the needle array-to-ring electrode. The flow velocity of the ionic wind is dependent on both the number of serial stages and the pressure loss. A maximum average flow velocity of 7.39 m/s, volumetric flow rate of 140 L/min, and energy conversion efficiency of 0.8% were achieved experimentally in this paper.

Geodetic Strain Observations and Return Period of the Strongest Earthquakes of a Given Seismic Source Zone

We present the basis for a method for estimating the return period of large and medium earthquakes that is independent of current deterministic and probabilistic approaches. The two standard techniques of seismic hazard assessment—probabilistic seismic hazard assessment (PSHA) and deterministic seismic hazard assessment (DSHA)—suffer from limited knowledge of seismic prehistory. A further weakness of PSHA is its requirement of homogeneous seismic activity within a seismic zone. Moreover, PSHA and DSHA were developed for seismically active areas and, thus, cannot reliably be used in areas of medium and low activity. In this paper we propose the combined use of geodetic strain rate data and the seismic moment data set determined for past seismic events. This combination represents a new and independent approach to estimation of future seismic activity. Using a modified version of Kostrov’s (Phys Solid Earth 1:23–40, 1974) equation and the catalogue of seismic moments, the minimum return period of the strongest earthquakes of a source area is estimated.

Effect of filler surface properties on structure, mechanical and tribological behavior of PTFE-carbon black composites

Effect of two grades of carbon black (CB) on structure, strength and tribological behavior of PTFE-CB composites is studied in the filler range of 10 mass%. It is found that differences in surface properties of the fillers used to determine the type of supermolecular structure evolved and patterns of variation of mechanical properties, friction and wear in response to increasing filler content. It is found that wear of low-filled PTFE-CB composites is dominated by delamination mechanism and wear resistance changes correlate with structural transformations of the composites. The maximum increase in wear resistance of the PTFE composites is reached at 1 mass% filling for both filler grades amounting to the factor of ∼40 for the CB grade with low surface activity and small specific surface area and a factor of ∼700 for the CB grade with high activity and high value of the specific surface area. It is first found that relative wear resistance increases in proportion to the specific surface area and, tentatively, activity of the surface centers of the CB filler used, which fact is attributed to the filler capacity to block and heal fatigue-induced cracking of the subsurface layer at friction.

Dynamic Responses of Calving Caribou to Oilfields in Northern Alaska

Past research has suggested that during the calving period, caribou (Rangifer tarandus) in Arctic Alaska generally avoid areas within 1 km of oilfield roads with traffic. However, avoidance is not absolute, and caribou may habituate to infrastructure (e.g., buildings, roads, well pads) and human activity. We conducted road-based surveys of caribou in oilfields on Alaska’s Arctic Coastal Plain during the late calving and post-calving periods of June in 2000–02. We recorded location, composition, and behavior of caribou groups located less than 1 km from active gravel roads and production pads. Caribou groups with calves were on average distributed farther from oilfield infrastructure than were groups without calves, but habituation to oilfield activities, indicated by decreased avoidance, occurred at similar rates for groups with and without calves. During the calving period, sighting rates were greater in areas of low human activity, and calf percentages tended to be greater at night when oilfield activity was reduced. Caribou groups were on average closer to infrastructure during the post-calving periods than during the calving periods in 2000 and 2001, but not in 2002. In 2002, when snow melted early, caribou groups were closer to infrastructure during the calving period than in 2000 and 2001, when snow melted later, emphasizing the importance of examining environmental variables when investigating the dynamic interactions of caribou and oilfields. Overall, caribou appeared to habituate to active oilfield infrastructure after the calving period in 2000, late in the calving period in 2001, and likely before our sampling period in 2002. The timing of annual rehabituation was positively correlated with timing of spring snowmelt. Land and wildlife managers can use information from this study to develop calving period-specific mitigation measures that are more effective and flexible.

The impact of reconstruction method on the quantification of DaTSCAN images

Reconstruction of DaTSCAN brain studies using OS-EM iterative reconstruction offers better image quality and more accurate quantification than filtered back-projection. However, reconstruction must proceed for a sufficient number of iterations to achieve stable and accurate data. This study assessed the impact of the number of iterations on the image quantification, comparing the results of the iterative reconstruction with filtered back-projection data. A striatal phantom filled with (123)I using striatal to background ratios between 2:1 and 10:1 was imaged on five different gamma camera systems. Data from each system were reconstructed using OS-EM (which included depth-independent resolution recovery) with various combinations of iterations and subsets to achieve up to 200 EM-equivalent iterations and with filtered back-projection. Using volume of interest analysis, the relationships between image reconstruction strategy and quantification of striatal uptake were assessed. For phantom filling ratios of 5:1 or less, significant convergence of measured ratios occurred close to 100 EM-equivalent iterations, whereas for higher filling ratios, measured uptake ratios did not display a convergence pattern. Assessment of the count concentrations used to derive the measured uptake ratio showed that nonconvergence of low background count concentrations caused peaking in higher measured uptake ratios. Compared to filtered back-projection, OS-EM displayed larger uptake ratios because of the resolution recovery applied in the iterative algorithm. The number of EM-equivalent iterations used in OS-EM reconstruction influences the quantification of DaTSCAN studies because of incomplete convergence and possible bias in areas of low activity due to the nonnegativity constraint in OS-EM reconstruction. Nevertheless, OS-EM using 100 EM-equivalent iterations provides the best linear discriminatory measure to quantify the uptake in DaTSCAN studies.

Assessment of faecal pollution and relative algal abundances in Lakes Oconee and Sinclair, Georgia, USA

AbstractWater quality was assessed for five subregions of Lake Oconee and Lake Sinclair in Georgia, USA. The areas were chosen for their levels of human impact, including: (i) suburban development >30 years old; (ii) modern suburban development; (iii) industry; (iv) agriculture; and (v) an area of low human activity. The measured temperature, pH, dissolved oxygen concentration and turbidity values were normal for oligotrophic lakes. Faecal pollution in the lakes was determined using the membrane filtration method (Method 1600) on mEI plates for enterococci. There was a positive correlation between turbidity and the number of faecal enterococci in the lakes. The faecal pollution level was higher for the old suburban and agricultural areas. Faecal pollution in the agricultural region of Lake Oconee exceeded EPA regulatory standards. The faecal pollution source was identified using polymerase chain reaction detection, with Bifidobacterium adolescentis being a marker of human faecal pollution, and bovine‐associated Bacteroides (BoBac) as a marker of cattle faecal pollution. Human faecal pollution was detected in the agricultural, old suburban and industrial areas of the lakes. In contrast, bovine faecal pollution was detected only in the agricultural area of Lake Oconee. Measurements of chlorophyll‐a and relative algal community abundance indicated the least‐impacted and modern suburban areas had significantly lower numbers of primary producers, being dominated by diatoms.

Antibodies to Flaviviruses in Wild Ducks Captured in Hokkaido, Japan: Risk Assessment of Invasive Flaviviruses

Recently, the distribution of Japanese encephalitis virus (JEV) and West Nile virus (WNV) has expanded into new territories. The invasion of WNV into Japan is of great concern. The migration of birds is suggested to be involved in the expanded distribution of these flaviviruses. In this study, 92 wild ducks--20 Anas poecilorhyncha (migratory breeders), 50 Anas platyrhynchos (undetermined), 16 Anas acuta (winter visitors), and 6 Anas penelope (winter visitors)--were captured in autumn of 2005 and 2006, in the central part of Hokkaido, a low JEV activity area. A seroepidemiologic analysis of flavivirus infections was conducted with 90% and 50% focus reduction neutralization tests (FRNT(90) and FRNT(50)). Of the 92 serum samples, 1 (1.1%) and 5 (5.4%) tested positive for WNV-specific and JEV-specific antibodies, respectively, in the FRNT(90), and 61 (66.3%) and 79 (85.9%) tested positive for WNV and JEV, respectively, in the FRNT(50). These results indicate that wild ducks in this study had been exposed to flaviviruses. The results together with the recognized distribution of flaviviruses and migratory routes of individual duck species strongly suggested that the birds captured in this study had been exposed to flaviviruses, including WNV, on the flyway, not in Hokkaido.

Spatial representations of odorants in olfactory bulbs of rats and mice: Similarities and differences in chemotopic organization

In previous studies, we mapped glomerular layer 2-deoxyglucose uptake evoked by hundreds of both systematically related and chemically distinct odorants in rat olfactory bulbs. To determine which principles of chemotopic organization revealed in these studies may be more fundamental and which may be more species typical, we now have characterized patterns of responses to 30 of these odorants in mice. We found that only a few odorants evoked their multiple foci of peak activity in exactly the same locations in the two species. In mice, as in rats, odorants that shared molecular features evoked overlapping patterns, but the locations of the feature-responsive domains often differed in rats and mice. In rats, increasing carbon number within a homologous series of aliphatic odorants is generally associated with rostral and ventral progressions of activity within domains responding to odorant functional group and/or hydrocarbon backbone. Such chemotopic progressions were not obvious in mice, which instead showed more abrupt differences in activated glomeruli within the domains for odorants differing by a single methylene group. Despite the differences, quantitative relationships between overall uptake patterns exhibited a similar organization with respect to odorant chemistry for the two species, probably as a result of partial overlaps of peak domains and more extensive overlaps in large, low-activity areas for rats and mice. We conclude that clustering responses to shared odorant features may be a general strategy for odor coding but that the specific locations of high-activity domains may be unique to a species.

Late Quaternary landscape development along the Rancho Marino coastal range front (south‐central Pacific Coast Ranges, California, USA)

AbstractLate Quaternary landscape development along the Rancho Marino coastal range front in the central‐southern Pacific Coast Ranges of California has been documented using field mapping, surveying, sedimentary facies analysis and a luminescence age determination. Late Quaternary sediments along the base of the range front form a single composite marine terrace buried by alluvial fans. Marine terrace sediments overlie two palaeoshore platforms at 5 m and 0 m altitude. Correlation with the nearby Cayucos and San Simeon sites links platform and marine terrace development to the 125 ka and 105 ka sea‐level highstands. Uplift rate estimates based on the 125 ka shoreline angle are 0.01–0.09 m ka−1 (mean 0.04 m ka−1), and suggest an increase in regional uplift along the coast towards the NW where the San Simeon fault zone intersects the coastline. Furthermore, such low rates suggest that pre‐125 ka uplift was responsible for most of the relief generation at Rancho Marino. The coastal range front landscape development is, thus, primarily controlled by post 125 ka climatic and sea‐level changes. Post 125 ka sea‐level lowering expanded the range front piedmont area to a width of 7.5 km by the 18 ka Last Glacial Maximum lowstand. This sea‐level lowering created space for alluvial fan building along the range front. A 45 ± 3 ka optically stimulated luminescence (OSL) age provides a basal age for alluvial fan building or marks the time by which distal alluvial fan sedimentation has reached 300 m from the range front slope. Fan sedimentation is related to climatic change, with increased sediment supply to the range front occurring during (1) glacial period cold stage maxima and/or (2) the Late Pleistocene–Holocene transition, when respective increases in precipitation and/or storminess resulted in hillslope erosion. Sea‐level rise after the 18 ka lowstand resulted in range front erosion, with elevated localised erosion linked to the higher relief and steeper slopes in the SE. This study demonstrates that late Quaternary coastal range front landscape development is driven by interplay of tectonics, climatic and sea‐level change. In areas of low tectonic activity, climatic and sea‐level changes dominate coastal landscape development. When the sea‐level controlled shoreline is in close proximity to the coastal range front, localised patterns of sedimentation and erosion are passively influenced by the pre‐125 ka topography. Copyright © 2008 John Wiley & Sons, Ltd.

A 6-bit 3.5-GS/s 0.9-V 98-mW Flash ADC in 90-nm CMOS

A 6-bit 3.5-GS/s flash ADC is reported. A load circuit with a clamp diode and a replica-biasing scheme is developed for low-voltage and high-speed operation. An acceleration capacitor is introduced for high-speed overdrive recovery of a comparator. An averaging and interpolation network is employed in this ADC. The interpolation factor is optimized considering random offset, active area, and systematic offset to realize low offset and small active area. The ADC is fabricated in a 90-nm CMOS process and occupies 0.15 mm2. It consumes 98 mW with a 0.9-V power supply. With Nyquist input, SNDR and SFDR at 3.5 GS/s are 31.18 dB and 38.67 dB, respectively.

Microstructured proton-conducting membranes by synchrotron-radiation-induced grafting

Selective exposures of poly(ethylene-alt-tetrafluoroethylene) (ETFE) films with hard X-rays through high aspect ratio Ni-masks were performed at the LIGA3 beamline of the “Angström Quelle Karlsruhe” (ANKA) to create patterns of radicals used as initiators for the grafting of styrene into the bulk of the ETFE films. Grafted films were then sulfonated to obtain proton-conducting membranes. The structure definition, as investigated by scanning electron microscopy (SEM), showed a perfect discrimination between exposed and shaded areas through all the film thickness. Structuring results in a more homogeneous appearance of the membrane without affecting the degree of grafting and proton conductivity in the grafted areas. In fuel cell tests the structured membranes showed slightly lower performance due to 10% lower active area, but had a significantly higher lifetime.

Modelling wildlife–human relationships for social species with mixed‐effects resource selection models

Summary Resource selection functions (RSF) have contributed to the conservation of species negatively affected by human activities. Despite these applications, two assumptions frequent many studies: the assumption of independence among groups in social species, and that selection is proportional to resource availability. This latter case is known as a functional response in resource selection, and may be especially important in human–wildlife relationships where there is a fitness cost of proximity to humans. Recent advances in generalized linear mixed models offer new ways to account for resource selection in social species and functional responses by accommodating correlations within hierarchical groups with random intercepts, and functional responses with random coefficients. We illustrate the application of mixed‐effects RSF models using a case study of resource selection by individual wolves Canis lupus living in packs as a function of human activity. In areas of low human activity, wolf resource selection was independent of proximity to humans. As human activity increased, wolves displayed a functional response selecting areas closer to human activity. With increasing human activity, however, wolves displayed spatio‐temporal avoidance of human activity during daylight. This could lead to behaviourally induced trophic cascades mediated by wolf avoidance of human activity, and fits within the framework of attractive sink habitats. Accounting for the hierarchical social structure of wolves clearly showed that the response of wolves to human disturbance was strongly correlated, but different, within packs, and that the correlation was strongest during winter and weakest during summer. Syntheses and applications. Failure to consider the social structure of wolves and the functional response to human activity would result in mistaken conclusions about wolf–human relationships. Our approach provides a unifying framework to understand the contradictory results of previous studies of wolf–human relationships and a template for future studies to evaluate effects of increasing human activity on wildlife.

Neotectonic development of drainage networks in the East Sudeten Mountains and monitoring of recent fault displacements (Czech Republic)

This paper presents results of morphotectonic research carried out in order to determine the neotectonic development of the drainage network in the NE spur of the Bohemian Massif (central Europe). The area studied comprises the north-eastern sector of the Rychlebské Mts, belonging to the Sudeten Mountains and the adjacent part of the Žulovská Hilly Land in the Sudetic Foreland (Czech Republic). Analysis of drainage network characteristics such as cross-sections, erosion rate, longitudinal river profiles, stream length-gradient index (SL) and investigation of alluvial fans/terraces was performed using detailed geomorphological mapping and field examination, and DEM data. Moreover, a reconstructed neotectonic evolution was compared with present-day fault movements obtained by fault monitoring using the TM71 deformeter. The deformeter was installed directly across faults in two karst caves in the study area within the NW–SE striking Sudetic Marginal Fault (SMF) zone. This zone is one of the morphologically most prominent neotectonic structures in central Europe, separating the Sudeten Mountains from the Sudetic Foreland. Morphotectonic research reveals that segments of enhanced erosion correspond well with increased SL indices, changes in valley cross-sections and anomalies in the longitudinal profiles. The beginnings of the stretches of increased headward erosion/rejuvenated erosional phase are concentrated at the foot of marginal slopes of the mountainous sector of the study area, which supports the hypothesis that uplift of the mountainous sector is still expressed in its relief. Alluvial fans/terraces of three levels recognized in the adjacent Žulovská Hilly Land are of Middle to Late Pleistocene age: Saalian 1 (240–280 ka), Saalian 2 (130–180 ka) and Weichselian (10–80 ka), respectively. They postdate the retreat of the last continental ice-sheet, which reached the study area in Elsterian 2 (400–460 ka). Their relative heights above the river channel are greater than terrace levels of the same age along the main Nysa Kłodzka River. The height differences attain 20 m at the highest level 1, at least 8 m at level 2, and up to 2–3 m at level 3. These discrepancies imply post-Saalian 1 uplift of the Žulovská Hilly Land relative to the topographically lower Nysa Kłodzka valley. Monitoring of present-day tectonic movements in the studied area revealed slow micro-displacements (hundredths to tenths of millimetres per year). The displacements have an aseismic character and the vertical component always prevails over the horizontal one. The inferred compressive stress comes generally from the southern sector, which would imply dextral transpression in the studied portion of the SMF, where the northern part is thrusting over the southern one. The trend of these present-day movements corresponds well with uplift of the studied area north of the SMF, which is also indicated by analysis of the drainage network. It is concluded that in areas of low tectonic activity the detailed study of individual characteristics of the drainage network, particularly their spatial relationships, as well as monitoring of fault micro-displacements can reveal rates and kinematics of ongoing tectonism.

Cross-National Analysis on Spices Research in the Asian Countries

This paper attempts to identify the high and low activity areas of Spices Research amongst the 36 Asian countries. This analysis is spread over a period of three decades 1968 – 2002 using HORT – CD (Horticultural Science) database. The major focus of this paper is to determine the priorities of the research interests. Subject trends, gaps and similarity of research efforts amongst the Asian scholars working in this field. Using correspondence analysis, the relationship between countries versus Spices Research and the dynamics of changes in research priorities, if any, during the study period are being highlighted. Results and implications of this analysis are presented and discussed directing towards policy Makers.

Method of Early Prediction on Source Rocks in Basins with Low Exploration Activity

Low exploration activity fields (deep formation, deep water and new exploration areas) are important for petroleum exploration. Source rock evaluation, the result of which will determine the exploration potential of a basin, is one of the most important aspects. Because all the evaluation parameters are almost unknown in an area of low exploration activity with sparse wells, the early evaluation of source rock is somewhat contradictory. Based on the framework of sequence stratigraphy, this paper presents a method of early prediction and comprehensive evaluation of source rocks. The method includes four aspects: (1) analysis of sequence stratigraphy to determine the main formation of source rocks; (2) prediction of seismic velocity and lithology to determine the thickness of source rocks; (3) prediction of vitrinite reflectance, based on seismic data to determine the maturation of source rocks; (4) comprehensive source rock evaluation. Using the method of sequence stratigraphy and geophysical techniques, this method successively solves the contradiction between low exploration activity and early evaluation of source rock and provides a new choice for an early prediction on source rocks in fields of low exploration activity.

TU-E-M100F-01: PET and SPECT Imaging in Treatment Planning Optimization

Conventional CT-based planning is anatomically-based. Advanced imaging techniques facilitate the incorporation of “functional” information into the planning process. For example, FDG-PET is being more commonly used to define GTVs for lung, cervix, head and neck. Similarly, MRI spectroscopy can identify metabolically-distinct tumor targets within the prostate. For normal tissue, MRI can localize critical areas of brain function. SPECT lung and heart imaging quantifies regional organ perfusion, a reasonable surrogate for function. We've conducted studies using SPECT lung and heart perfusion to minimize and monitor RT-induced normal tissue injury. In the lung, “incidental” dose can be steered to the lesser functioning regions. IMRT may be particularly useful in exploiting these regional functional heterogeneities. We have shown that SPECT guidance can reduce the average functional lung above 20 Gy and 30 Gy by ≈ 15% and 14%, respectively. Carefully selecting beam orientations can provide further reductions in irradiated functional lung. Incorporating nuclear medicine imaging into radiation planning is challenging. Some planning systems do not readily accept nuclear medicine images. While CT imaging can be readily gated to respiration, nuclear medicine imaging is not necessarily gated. Limitations of nuclear medicine scanners may prevent scanning patients in the treatment position/cradle. These factors may introduce inaccuracies in registering nuclear images to the planning CT.Conversely, combined nuclear medicine/CT scanners may facilitate image registration.The resolution of nuclear medicine imaging is typically inferior to CT/MR. Therefore, abnormalities and anatomic findings on CT should not be readily dismissed if they are not seen on nuclear scans, since the resolution is relatively limited. Further, one needs to decide exactly how to use the nuclear medicine information. Quantitative nuclear data can be grossly “binned” and areas of high vs. low activity can be defined and considered as separate regions for optimization. Alternatively, one can try to consider the full range of nuclear-activities (i.e. more finely binning the volume in areas of graded activity). However, it is not clear if the SPECT/PET activity is always linearly related to biological/functional information. More fundamentally, there remains controversy regarding what biological/functional attribute is actually being imaged by some nuclear scans. The field of functional-based planning is rapidly evolving and likely will play a major role in the future of RT. However, given the uncertainties, care should be taken when radiation techniques deviate wildly from the standard/traditional approaches. Research sponsored, in part, by Varian Medical Systems, The Lance Armstrong Foundation, the Department of Defense, and the National Institute of Health (CA69579, CA115748). Educational Objectives: To understand the 1. difference between anatomic and functional-based planning. 2. utility of PET imaging to define GTV's. 3. utility of SPECT and MRI in defining normal tissues. 4. potential shortcomings of functional imaging for treatment planning.