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miR-125a-5p regulation increases phosphorylation of FAK that contributes to imatinib resistance in gastrointestinal stromal tumors

Highlights: • Phosphorylation of FAK is regulated by PTPN18 and miR-125a-5p. • pFAK level is higher in imatinib-resistant than imatinib-sensitive GIST882 cells. • FAK inihibitor treatment in imatinib-resistant cells increases imatinib-induced apoptosis. • Blocking FAK phosphorylation rescues miR-125a-5p mediated imatinib resistance. The use of imatinib mesylate has greatly improved the clinical outcome for gastrointestinal stromal tumor (GIST) patients. However, imatinib resistance is still a major clinical challenge, and the molecular mechanisms are not fully understood. We have previously shown that miR-125a-5p and its mRNA target PTPN18 modulate imatinib response in GIST cells. Herein, we evaluated phosphorylated FAK (pFAK) as a candidate downstream target of PTPN18 and the possible association of this regulation with imatinib resistance in GIST. FAK and pFAK expressions were evaluated in GIST882 cells transfected with short hairpin RNA or short interfering RNA targeting PTPN18 or miR-125a-5p mimic, imatinib-resistant GIST882R subclones and clinical samples using Western blot analyses. FAK phosphorylation was blocked using the FAK inhibitor 14 (FAKi) and the effects on cell viability and apoptosis were evaluated using WST-1 assay and cleaved PARP expression. Clinical associations of FAK and pFAK expression with imatinib resistance, KIT mutation and patient outcome were assessed by Fisher's exact test or log-rank test. Over-expression of miR-125a-5p and silencing of PTPN18 increased pFAK, but not FAK, expression in GIST cells. Higher pFAK expression was observed in the GIST882R subclones with acquired imatinib resistance compared to their imatinib-sensitive parental cells. Treatment with FAKi in imatinib-resistant GIST882R cells reduced cell viability and increased apoptosis upon imatinib treatment. Additionally, FAKi could rescue the imatinib resistance effect mediated by miR-125a-5p over-expression. In clinical samples, high FAK and pFAK expressions were associated with KIT mutation status, and high FAK expression was also associated with metastasis in GIST. Higher pFAK was found in cases with shorter overall survival. Our findings highlight an important role for miR-125a-5p regulation and its downstream target pFAK for imatinib resistance in GIST. pFAK and FAK may have prognostic values in GIST.

60 APPLIED LIFE SCIENCES↗

The Impact of Controlled Rest on Neurobehavioral Outcomes at Top-of-Descent

INTRODUCTION: Long and irregular working hours can lead to fatigue in aviation operations. In some regions, a short nap taken on the flight deck (known as controlled rest) can be used as a countermeasure to unexpected in-flight sleepiness. We aimed to investigate the impact of taking controlled rest on neurobehavioral measures at top-of-descent. METHODS: Data from 120 long-haul (> 6 h flight duration), unaugmented flights were analyzed (n = 31 pilots). Pilots wore actigraphs and completed sleep logs before and during trips. At pre-flight and top-of-descent, pilots completed a 5-minute psychomotor vigilance task (PVT) and Karolinska Sleepiness Scale (KSS). A series of mixed-effects models were conducted to assess the impact of controlled rest on outcome measures at top-of-descent. Sleep duration in the prior 48 hours, timing of the flight, and pre-flight scores for each measure were included as covariates. RESULTS: Due to missing data, complete data from 76 flights (n = 28 participants) were available in the models examining the PVT metrics, and data from 83 flights (n = 29 participants) were available in the analyses of the KSS. Pilots who took controlled rest had faster response speeds at top-of-descent (p = .03, η2p = 0.07; estimated marginal mean [EMM] = 4.19, standard error [SE] = 0.07, 95% CI [4.08, 4.29]) than those who did not take controlled rest (EMM = 4.00, SE = 0.05, 95% CI [3.86, 4.14]). There were no differences by controlled rest status for KSS scores and PVT lapses (p values > .05, η2p values ≤ 0.01). DISCUSSION: Our results suggest that taking controlled rest may improve vigilant attention at critical phases of flight and, thus, may be a useful fatigue management tool during unaugmented flights. Further research is necessary to determine the impact of factors on the decision to take controlled rest (e.g., airline culture, personal preference) and how the controlled rest policy is applied in practice.

aviation↗

Cradle-to-Grave: Assessment Methods for Hazardous Waste Management

The Resource Conservation and Recovery Act (RCRA) was passed to set up a framework for the proper management of waste. The 40CFR260-273 regulation established the regulatory framework to handle solid and hazardous waste, from the point of generation to its disposal; or cradle-to-grave management. Per these regulations, a hazardous waste generator is responsible for its waste from initial generation through its ultimate disposal and beyond. Nothing will relinquish a generator of this responsibility. There is no expiration date or time limit, and hiring a someone else to transport and dispose of waste does not transfer responsibility. If an incident occurs at any point during the life cycle of a waste, the generator can be held liable. The first step to compliance with RCRA is proper characterization of the waste. Waste may either be listed specifically or may show a characteristic as defined in the regulation: Is my waste hazardous? Why is it Hazardous? What should I do as a generator? Plan chemical use: - Create a chemical inventory for your research project. - Use existing chemicals if available instead of ordering new ones. - Brainstorm methods that will help to reduce toxicity and minimize waste. Waste Inventory: - Label all waste bottles with: ID no., What is it, Whose is it, Hazards, and Date. - Add waste containers into the inventory log. - Initiate/complete the container sheet to describe the waste. Satellite Areas: - Store waste in containers compatible with the waste with lids on tight. - Store waste containers properly and segregate them according to their specific hazards. - Use secondary containment for liquids. Store acids and bases separately; apart from cyanides or sulfides. Acids should never be put into steel containers. Water-reactive, strong acids such as organic acid halides, organic acid anhydrides, inorganic acid anhydrides, and strong acidic salts must be kept apart from both alkalis and water. Oxidizing agents must be kept apart from reducing agents and organic compounds. Water-reactive agents must be stored apart from water, aqueous solutions, and acids. Air-reactive materials must be packed in containers that are sealed off from the atmosphere. Explosive and shock-sensitive materials present risks that require special handling.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Identification of blind geothermal resources in Surprise Valley, CA, using publicly available groundwater well water quality data

Geothermal resource exploration is generally limited to areas with surface expressions of thermal activity (fumaroles and hot springs), or relies on expensive geophysical exploration techniques. The hidden subsurface distribution of geothermal fluids has been identified using a free and publicly available water quality dataset from agricultural and domestic water wells in Surprise Valley, northeastern California. Thermally evolved waters in Surprise Valley have element ratios that vary in response to Ca carbonate and Mg silicate mineral precipitation, and have elevated total dissolved solids (TDS). The arid climate in Surprise Valley leads to surface water evaporation in a closed basin, producing high TDS Na-Cl-CO 3 -SO 4 brines in three ephemeral alkali lakes and in shallow groundwater under elevated soil CO 2 conditions. Evaporated fluids in Surprise Valley follow a chemical divide that leads to Ca carbonate and Mg silicate mineral precipitation. Plots of dissolved element ratios can be used to distinguish groundwater affected by evaporation from water affected by thermal water-rock interaction, however it is challenging to select components for plotting that best illustrate different fluid evolution mechanisms. Here, we use a principal component analysis of centered log-ratio transformed data, coupled with geochemical models of fluid evaporation and thermal mixing pathways, to identify components to plot that distinguish between groundwater samples influenced by evaporation from those influenced by thermal processes. We find that groundwater samples with a thermal signature come from wells that define a coherent, linear geographical distribution that closely matches the location of known and inferred faults. Finally, modification of the general approach employed here provides promise for identifying blind geothermal resources in other locations, by applying low-cost geochemical modeling and statistical techniques to areas where large groundwater quality geochemical datasets are available.

15 GEOTHERMAL ENERGY↗

WE-G-BRF-07: Non-Circular Scanning Trajectories with Varian Developer Mode

Purpose: Cone-beam CT (CBCT) in image-guide radiation therapy (IGRT) typicallyacquires scan data via the circular trajectory of the linearaccelerator's (linac) gantry rotation. Though this lends itself toanalytic reconstruction algorithms like FDK, iterative reconstructionalgorithms allow for a broader range of scanning trajectories. Weimplemented a non-circular scanning trajectory with Varian's TrueBeamDeveloper Mode and performed some preliminary reconstructions toverify the geometry. Methods: We used TrueBeam Developer Mode to program a new scanning trajectorythat increases the field of view (FOV) along the gantry rotation axiswithout moving the patient. This trajectory consisted of moving thegantry in a circle, then translating the source and detector along theaxial direction before acquiring another circular scan 19 cm away fromthe first. The linear portion of the trajectory includes an additional4.5 cm above and below the axial planes of the source's circularrotation. We scanned a calibration phantom consisting of a lucite tubewith a spiral pattern of CT spots and used the maximum-likelihoodalgorithm to iteratively reconstruct the CBCT volume. Results: With the TrueBeam trajectory definition, we acquired projection dataof the calibration phantom using the previously described trajectory.We obtained a scan of the treatment couch for log normalization byscanning with the same trajectory but without the phantom present.Using the nominal geometric parameters reported in the projectionheaders with our iterative reconstruction algorithm, we obtained acorrect reconstruction of the calibration phantom. Conclusion: The ability to implement new scanning trajectories with the TrueBeamDeveloper Mode enables us access to a new parameter space for imagingwith CBCT for IGRT. Previous simulations and simple dual circle scanshave shown iterative reconstruction with non-circular trajectories canincrease the axial FOV with CBCT. Use of Developer Mode allowsexperimentally testing these and other new scanning trajectories. Support was provided in part by the University of Chicago Research Computing Center, Varian Medical Systems, and NIH Grants 1RO1CA120540, T32EB002103, S10 RR021039 and P30 CA14599. The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the supporting organizations.

60 APPLIED LIFE SCIENCES↗

Detection of GRB 060927 at zeta = 5.47: Implications for the Use of Gamma-Ray Bursts as Probes of the End of the Dark Ages

We report on follow-up observations of the gamma-ray burst GRB 060927 using the robotic ROTSE-IIIa telescope and a suite of larger aperture groundbased telescopes. An optical afterglow was detected 20 s after the burst, the earliest rest-frame detection of optical emission from any GRB. Spectroscopy performed with the VLT about 13 hours after the trigger shows a continuum break at lambda approx. equals 8070 A, produced by neutral hydrogen absorption at zeta = 5.6. We also detect an absorption line at 8158 A which we interpret as Si II lambda 1260 at zeta = 5.467. Hence, GRB 060927 is the second most distant GRB with a spectroscopically measured redshift. The shape of the red wing of the spectral break can be fitted by a damped Ly(alpha) profile with a column density with log(N(sub HI)/sq cm) = 22.50 +/- 0.15. We discuss the implications of this work for the use of GRBs as probes of the end of the dark ages and draw three main conclusions: i) GRB afterglows originating from zeta greater than or approx. equal to 6 should be relatively easy to detect from the ground, but rapid near-infrared monitoring is necessary to ensure that they are found; ii) The presence of large H I column densities in some GRBs host galaxies at zeta > 5 makes the use of GRBs to probe the reionization epoch via spectroscopy of the red damping wing challenging; iii) GRBs appear crucial to locate typical star-forming galaxies at zeta > 5 and therefore the type of galaxies responsible for the reionization of the universe.

Ruiz-Velasco, A. E.↗

Remote Sensing Approach for Monitoring Tree Health Adjacent to Transmission Corridors

This study presents an initial proof-of-concept for a satellite-based remote sensing approach to identify and monitor potential areas of poor tree health across the entire BPA service territory on an annual basis. We tested three variants of “delta peak NDVI” ( ΔPN ) change detection metrics that express interannual variation in primary productivity relative to a baseline by comparing ΔPN values for known insect/disease disturbances and nearby reference locations. All three metrics showed promise for detecting poor tree health in the year during disturbance, but the metric based on the difference from the long-term (2016-2024) median ( Δ Med PN ) was preferred due to its responsiveness to change in the years during and after disturbance, resilience to interannual variation, and ease of interpretation as being above or below normal. Comparison of Δ Med PN grouped by relative severity of disturbance indicated it was not sensitive enough to detect “low” severity disturbances, as mapped by USGS’s LANDFIRE program, but could distinguish “moderate” and “high” severity disturbances from reference locations. These findings informed selection of a threshold for Δ Med PN , which was combined with areas exhibiting negative NDVI to map potential areas of concern. Visual inspection of before/after high-resolution imagery and NDVI time series showed that many areas of concern aligned with visible signs of defoliation and die-off as well as other types of disturbance (e.g., landslides, logging, road grading, flooding). Some areas of concern are thought to be false detections caused by persistent shadow, and some could not be explained with visual inspection due to spatiotemporal limitations of before/after imagery. In summary, our approach shows promise for large-scale monitoring of tree health adjacent to BPA transmission lines, but additional work is recommended to improve model sophistication and remove noise.

24 POWER TRANSMISSION AND DISTRIBUTION↗

COLD-MODE ACCRETION: DRIVING THE FUNDAMENTAL MASS–METALLICITY RELATION AT z ∼ 2

We investigate the star formation rate (SFR) dependence on the stellar mass and gas-phase metallicity relation at z = 2 with MOSFIRE/Keck as part of the ZFIRE survey. We have identified 117 galaxies (1.98 ≤ z ≤ 2.56), with 8.9 ≤ log( M / M {sub ⊙}) ≤ 11.0, for which we can measure gas-phase metallicities. For the first time, we show a discernible difference between the mass–metallicity relation, using individual galaxies, when dividing the sample by low (<10 M {sub ⊙} yr{sup −1}) and high (>10 M {sub ⊙} yr{sup −1}) SFRs. At fixed mass, low star-forming galaxies tend to have higher metallicity than high star-forming galaxies. Using a few basic assumptions, we further show that the gas masses and metallicities required to produce the fundamental mass–metallicity relation and its intrinsic scatter are consistent with cold-mode accretion predictions obtained from the OWLS hydrodynamical simulations. Our results from both simulations and observations are suggestive that cold-mode accretion is responsible for the fundamental mass–metallicity relation at z = 2 and it demonstrates the direct relationship between cosmological accretion and the fundamental properties of galaxies.

79 ASTRONOMY AND ASTROPHYSICS↗

Dependence of Photosynthetic Capacity, Photosynthetic Pigment Allocation, and Carbon Storage on Nitrogen Levels in Foliage of Aspen Stands

The role of foliar nitrogen (N) in the seasonal dynamics and vertical canopy distribution of photosynthetic pigments, photosynthetic capacity, and carbon (C) storage was investigated in boreal broadleaved species. The study was conducted at two different aged stands (60 y and 15 y) in 1994 and 1996 in Saskatchewan, Canada as part of the Boreal Ecosystem-Atmosphere Study (BOREAS). Foliage in upper and lower strata was examined for aspen (Populus tremuloides Michx.) and its associated hazelnut shrub (Corylus americana Walt.). We determined that C accumulation, expressed as dry mass per unit leaf area (mg C cm (exp -2)), was linearly dependent on N content (approximately 0.3- 3.5 mg N cm (exp -2))(r (exp 2) = 0.93, n=383, P less than 0.001) when eleven foliage groups were defined according to species, site, and developmental stage. C assembly was greatest in the upper aspen strata of both sites (seasonal average, 40.1 plus or minus 0.6 mg C cm (exp -2)), intermediate in the lower aspen strata (32.7 plus or minus 0.6), and considerably lower, and similar, in the hazelnut shrub layers (23.7 plus or minus 0.6) and in expanding aspen leaves (23.8 plus or minus 0.5); the lowest C assembly per unit N occurred in the two youngest, emerging leaf groups (17.1 plus or minus 0.6). Other relationships among physiological and biochemical variables were typically non-linear and were confounded by inclusion of the three groups of young (i.e., emerging or expanding) leaves, unless these were separately identified. Net C uptake, measured as photosynthetic capacity (A (sub max), micromole CO2 m (exp -2) s (exp -1)), was greater in aspen throughout the season, and optimal in mid-summer at a C:N ratio of approximately 18 (approximately 2.3 %N). When young leaves were excluded and logarithms of both variables were used, A (sub max) was approximately linearly dependent on N (mg N cm (exp-2) (r (exp 2) = 0.85, n= 193, P less than 0.001), attributed to incorporation of N into photosynthetic complexes and enzymes. In mature leaves, differences in pigment content vs. N among canopy strata were accentuated when N was expressed per unit leaf area (Mg cm (exp -2)) . However, the simplest log-linear relationship between a pigment variable and N was obtained for a ratio describing the relative allocation of photosynthetic pigment to Chl a (Chl a/[Chl b + carotenoids], microgram cm (exp -2)/ microgram cm-2) vs. %N (r (exp 2) = 0.90, n=343, P less than 0.001). Attainment of comparable A (sub max) Chl a content and relative Chl a allocation per unit N (mg cm (exp -2)) was achieved at different foliar N levels per canopy group: the lowest N requirement was for hazelnut leaves in the lowest, shaded stratum at the older, closed canopy site; the highest N requirement was in aspen leaves of the upper-most stratum at the younger, more open canopy site. These results highlight the differences in physiological responses between young and fully expanded leaves and show that sustaining those foliar constituents and processes important to C balance may require higher foliar N levels in leaves of establishing vs. mature aspen stands. There may be implications for remote-sensing assessments made for carbon balance in springtime, or over a landscape mosaic comprised of different aged stands.

Middleton, Elizabeth M.↗

Pahute Mesa Well Development and Testing Analyses for Wells ER-20-7, ER-20-8 #2, and ER-EC-11, Revision 1

This report analyzes the following data collected from ER-20-7, ER-20-8 No.2, and ER-EC-11 during WDT operations: (1) Chemical indicators of well development (Section 2.0); (2) Static hydraulic head (Section 3.0); (3) Radiochemistry and geochemistry (Section 4.0); (4) Drawdown observed at locations distal to the pumping well (Section 5.0); and (5) Drilling water production, flow logs, and temperature logs (Section 6.0). The new data are further considered with respect to existing data as to how they enhance or change interpretations of groundwater flow and transport, and an interim small-scale conceptual model is also developed and compared to Phase I concepts. The purpose of well development is to remove drilling fluids and drilling-associated fines from the formation adjacent to a well so samples reflecting ambient groundwater water quality can be collected, and to restore hydraulic properties near the well bore. Drilling fluids can contaminate environmental samples from the well, resulting in nonrepresentative measurements. Both drilling fluids and preexisting fines in the formation adjacent to the well can impede the flow of water from the formation to the well, creating artifacts in hydraulic response data measured in the well.

54 ENVIRONMENTAL SCIENCES↗

Steep Decay Phase Shaped by the Curvature Effect. I. Flux Evolution

The curvature effect may be responsible for the steep decay phase observed in gamma-ray bursts. To test the curvature effect with observations, the zero time point t {sub 0} adopted to plot the observer time and flux on a logarithmic scale should be appropriately selected. In practice, however, the true t {sub 0} cannot be directly constrained from the data. Thus, we move t {sub 0} to a certain time in the steep decay phase, which can be easily identified. In this situation, we derive an analytical formula to describe the flux evolution of the steep decay phase. The analytical formula reads as F{sub ν}∝(1+ t-tilde {sub obs}/ t-tilde {sub c}){sup −α}, with α( t-tilde {sub obs})=2+∫{sub 0}{sup log(1+ t-tilde {sub o}{sub b}{sub s}/ t-tilde {sub c})} β(τ)d[log(1+τ/ t-tilde {sub c})]/log(1+ t-tilde {sub obs}/ t-tilde {sub c}), where F {sub ν} is the flux observed at frequency ν, t-tilde {sub obs} is the observer time by setting t {sub 0} at a certain time in the steep decay phase, β is the spectral index estimated around ν, and t-tilde {sub c} is the decay timescale of the phase with t-tilde {sub obs}⩾0. We test the analytical formula with the data from numerical calculations. It is found that the analytical formula presents a good estimate of the evolution of the flux shaped by the curvature effect. Our analytical formula can be used to confront the curvature effect with observations and estimate the decay timescale of the steep decay phase.

79 ASTRONOMY AND ASTROPHYSICS↗

Response of terrestrial microorganisms to a simulated Martian environment

Soil samples from Cape Canaveral were subjected to a simulated Martian environment and assayed periodically over 45 days to determine the effect of various environmental parameters on bacterial populations. The simulated environment was based on the most recent available data, prior to the Viking spacecraft, describing Martian conditions and consisted of a pressure of 7 millibars, an atmosphere of 99.9% CO2 and 0.1% O2, a freeze-thaw cycle of -65 C for 16 h and 24 C for 8 h, and variable moisture and nutrients. Reduced pressure had a significant effect, reducing growth under these conditions. Slight variations in gaseous composition of the simulated atmosphere had negligible effect on growth. The freeze-thaw cycle did not inhibit growth, but did result in a slower rate of decline after growth had occurred. Dry samples exhibited no change during the 45-day experiment, indicating that the simulated Martian environment was not toxic to bacterial populations. Psychrotrophic organisms responded more favorably to this environment than mesophiles, although both types exhibited increases of approximately 3 logs in 7 to 14 days when moisture and nutrients were available.

Foster, T. L.↗

Long-term soil transplant simulating climate change with latitude significantly alters microbial temporal turnover

To understand soil microbial community stability and temporal turnover in response to climate change, a long-term soil transplant experiment was conducted in three agricultural experiment stations over large transects from a warm temperate zone (Fengqiu station in central China) to a subtropical zone (Yingtan station in southern China) and a cold temperate zone (Hailun station in northern China). Annual soil samples were collected from these three stations from 2005 to 2011, and microbial communities were analyzed by sequencing microbial 16S ribosomal RNA gene amplicons using Illumina MiSeq technology. Our results revealed a distinctly differential pattern of microbial communities in both northward and southward transplantations, along with an increase in microbial richness with climate cooling and a corresponding decrease with climate warming. The microbial succession rate was estimated by the slope (w value) of linear regression of a log-transformed microbial community similarity with time (time–decay relationship). Compared with the low turnover rate of microbial communities in situ (w=0.046, P<0.001), the succession rate at the community level was significantly higher in the northward transplant (w=0.058, P<0.001) and highest in the southward transplant (w=0.094, P<0.001). Climate warming lead to a faster succession rate of microbial communities as well as lower species richness and compositional changes compared with in situ and climate cooling, which may be related to the high metabolic rates and intense competition under higher temperature. This study provides new insights into the impacts of climate change on the fundamental temporal scaling of soil microbial communities and microbial phylogenetic biodiversity.

54 ENVIRONMENTAL SCIENCES↗

Effects of Granular Control on Customers’ Perspective and Behavior with Automated Demand Response Systems

Automated demand response (Auto-DR) is expected to close the loop between buildings and the grid by providing machine-to-machine communications to curtail loads without the need for human intervention. Hence, it can offer more reliable and repeatable demand response results to the grid than the manual approach and make demand response participation a hassle-free experience for customers. However, many building operators misunderstand Auto-DR and are afraid of losing control over their building operation. To ease the transition from manual to Auto-DR, we designed and implemented granular control of Auto-DR systems so that building operators could modify or opt out of individual load-shed strategies whenever they wanted. This paper reports the research findings from this effort demonstrated through a field study in large commercial buildings located in New York City. We focused on (1) understanding how providing granular control affects building operators’ perspective on Auto-DR, and (2) evaluating the usefulness of granular control by examining their interaction with the Auto-DR user interface during test events. Through trend log analysis, interviews, and surveys, we found that: (1) the opt-out capability during Auto-DR events can remove the feeling of being forced into load curtailments and increase their willingness to adopt Auto-DR; (2) being able to modify individual load-shed strategies allows flexible Auto-DR participation that meets the building’s changing operational requirements; (3) a clear display of automation strategies helps building operators easily identify how Auto-DR is functioning and can build trust in Auto-DR systems.

Schetrit, Oren↗

Air classification of forest residue for tissue and ash separation efficiency

The goal of this Case Study was to evaluate the performance of air classification of logging residues toward meeting conversion CMAs for carbon and ash contents, as compared to the static status quo Base Case system in which the residues are first dried and then ground in a hammer mill with a 6 mm screen and fines < 1.18 mm are removed. Also considered were moisture and ash impacts on throughput and Overall Operating Effectiveness (OOE), as well as delivered feedstock cost and minimum fuel selling price (MFSP). Laboratory data on the impacts of fan speed and moisture content on the separation efficiency of soil ash, needles and bark from white wood were received from FCIC Subtask 5.2. Average throughput and energy consumption data were obtained from the Bioenergy Feedstock National User Facility (BFNUF) for the same air classifier. These data were utilized to develop the necessary response surface equations to perform throughput analysis using discrete event simulation. Because the Base Case status quo system utilizes drying prior to grinding, we modeled the Case Study with drying prior to air classification and subsequent grinding of the separated white wood to isolate the individual quality and cost impacts of air classification relative to the Base Case system. Key takeaways from this Case Study are that air classification improves the quality of the final material, but increases the production cost, especially when lights are disposed; this becomes a tradeoff between increased conversion yield and the extra cost. Removing material should be done as early in the process as possible. Each operation that occurs prior to removing the material increases the cost of the disposed material and leads to wasted energy expenditures. As processes are included or modified, the impact on monetary and energy cost should be included in the decision process. Identifying alternative uses and the associated value for material that is separated from the feedstock stream will have a significant impact on the delivered cost of the material. Although there was an increase in production cost by adding air classification, there was a resulting benefit to the MFSP when meeting or exceeding all of the conversion CMAs; this was an important finding that should be explored further with FCIC Subtask 8.3 and potentially FCIC Task 6.

09 BIOMASS FUELS↗

The rates and time-delay distribution of multiply imaged supernovae behind lensing clusters

Time delays of gravitationally lensed sources can be used to constrain the mass model of a deflector and determine cosmological parameters. We here present an analysis of the time-delay distribution of multiply imaged sources behind 17 strong lensing galaxy clusters with well-calibrated mass models. We find that for time delays less than 1000 days, at z = 3.0, their logarithmic probability distribution functions are well represented by P(log Δt) = 5.3 × 10{sup −4}Δt{sup β-tilde}/M{sub 250}{sup 2β-tilde}, with β-tilde = 0.77, where M{sub 250} is the projected cluster mass inside 250 kpc (in 10{sup 14}M{sub ☉}), and β-tilde is the power-law slope of the distribution. The resultant probability distribution function enables us to estimate the time-delay distribution in a lensing cluster of known mass. For a cluster with M{sub 250} = 2 × 10{sup 14}M{sub ☉}, the fraction of time delays less than 1000 days is approximately 3%. Taking Abell 1689 as an example, its dark halo and brightest galaxies, with central velocity dispersions σ≥500kms{sup −1}, mainly produce large time delays, while galaxy-scale mass clumps are responsible for generating smaller time delays. We estimate the probability of observing multiple images of a supernova in the known images of Abell 1689. A two-component model of estimating the supernova rate is applied in this work. For a magnitude threshold of m{sub AB} = 26.5, the yearly rate of Type Ia (core-collapse) supernovae with time delays less than 1000 days is 0.004±0.002 (0.029±0.001). If the magnitude threshold is lowered to m{sub AB} ∼ 27.0, the rate of core-collapse supernovae suitable for time delay observation is 0.044±0.015 per year.

79 ASTRONOMY AND ASTROPHYSICS↗

A modified hypoxia-based TCP model to investigate the clinical outcome of stereotactic hypofractionated regimes for early stage non-small-cell lung cancer (NSCLC)

Purpose: Stereotactic body radiotherapy (SBRT) has been applied to lung tumors at different stages and sizes with good local tumor control (LC) rates. The linear quadratic model (LQM), in its basic formulation, does not seem to be appropriate to describe the response to radiotherapy for clinical trials, based on a few fractions. Thus, the main aim of this work was to develop a model, which takes into account the hypoxic cells and their reoxygenation. Methods: A parameter named B has been introduced in a modified tumor control probability (TCP) from LQM and linear-quadratic-linear model (LQLM), and represents the fraction of hypoxic cells that survive and become oxygenated after each irradiation. Based on published trials evaluating LC at 3 yr (LC3), values of B were obtained by maximum likelihood minimization between predicted TCP and clinical LC3. Two oxygen enhancement ratio (OER) parameter sets (1 and 2) from literature have been adopted to calculate the B-factors. Initial hypoxic cell fractions ({eta}{sub h}) from 0.05 to 0.50 were assumed. Log-likelihood (L) and Akaike information criterion (AIC) were determined in an independent clinical validation dataset. Results: The B-values of modified TCPs spanned the whole interval from 0 to 1, depending on the fractionation scheme (number of fractions and dose/fraction), showing a maximum (close to 1) at doses/fraction of 8-12 Gy. The B-values calculated using the OER parameter set 1 exhibited a smoother falloff than set 2. An analytical expression was derived to describe the B-value's dependence on the fractionation scheme. The R{sup 2}-adjusted values varied from 0.63 to 0.67 for LQ models and OER set 1 and from 0.75 to 0.78 for LQ model and OER set 2. Lower values of R{sup 2}-adjusted were found for LQLM and both OER sets. L and AIC, calculated using a fraction of {eta}{sub h} = 0.15 and the B-value from the authors analytical expression were higher than for other {eta}{sub h}-values, irrespective of model or OER set. Conclusions: The authors model allows to predict the clinical outcome associated with SBRT treatment, taking into account both direct killing and indirect vasculature or stromal damage.

61 RADIATION PROTECTION AND DOSIMETRY↗

Prognostic Role of the Immunoscore for Patients with Urothelial Carcinoma of the Bladder Who Underwent Radical Cystectomy

Background: Increasing evidence suggests that cancer progression is strongly influenced by the host immune response, which is represented by immune cell infiltrates. The T-lymphocyte-based Immunoscore is reported to be a reliable prognostic factor in colon cancer, but its significance in urothelial carcinoma of the bladder (UCB) is at an early stage of exploration. This study aimed to determine whether the tumor immune infiltrate, as evaluated by the Immunoscore, could act as a useful prognostic marker for UCB patients who have undergone radical cystectomy (RC). Methods: In this study, immunohistochemistry was used to examine the Immunoscore of 221 UCB patients who underwent RC. The Immunoscore of the patients was determined by the densities of CD3+ and CD8+ T cells at the tumor center and the invasive margin. Results: A highly significant association between a low Immunoscore and a shortened patient survival (P < 0.001, log-rank test) was demonstrated. In different subsets of UCB patients, a low Immunoscore also was a prognostic indicator of pT ≤ 2, pN(–)-status tumors, negative vascular invasion, or both (P < 0.05). Importantly, the Immunoscore together with the patient’s pT status provided significant independent prognostic parameters in the multivariate analysis (P < 0.05). Furthermore, a significant correlation (P = 0.003) of a low Immunoscore with an increased UCB labeling index of Ki-67 (a cell proliferation marker) was observed in this UCB cohort. Conclusions: The findings suggest that the Immunoscore, as examined by immunohistochemistry, might serve as a novel prognostic marker for UCB patients who have undergone RC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗