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At least 217 records · Page 12

Severe Late Toxicities Following Concomitant Chemoradiotherapy Compared to Radiotherapy Alone in Cervical Cancer: An Inter-era Analysis

Purpose: To compare rates of severe late toxicities following concomitant chemoradiotherapy and radiotherapy alone for cervical cancer. Methods and Materials: Patients with cervical cancer were treated at a single institution with radiotherapy alone or concomitant chemoradiotherapy for curative intent. Severe late toxicity was defined as grade {>=}3 vaginal, urologic, or gastrointestinal toxicity or any pelvic fracture, using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE), occurring {>=}6 months from treatment completion and predating any salvage therapy. Severe late toxicity rates were compared after adjusting for pertinent covariates. Results: At 3 years, probability of vaginal severe late toxicity was 20.2% for radiotherapy alone and 35.1% for concomitant chemoradiotherapy (P=.026). At 3 years, probability of skeletal severe late toxicity was 1.6% for radiotherapy alone and 7.5% for concomitant chemoradiotherapy (P=.010). After adjustment for case mix, concomitant chemoradiotherapy was associated with higher vaginal (hazard ratio [HR] 3.0, 95% confidence interval [CI], 1.7-5.2, P<.001), and skeletal (HR 7.0, 95% CI 1.4-34.1, P=.016) severe late toxicity. Compared to high dilator compliance, moderate (HR 3.6, 95% CI 2.0-6.5, P<.001) and poor (HR 8.5, 95% CI 4.3-16.9, P<.001) dilator compliance was associated with higher vaginal severe late toxicity. Age >50 was associated with higher vaginal (HR 1.8, 95% CI 1.1-3.0, P=.013) and skeletal (HR 5.7, 95% CI 1.2-27.0, P=.028) severe late toxicity. Concomitant chemoradiotherapy was not associated with higher gastrointestinal (P=.886) or urologic (unadjusted, P=.053; adjusted, P=.063) severe late toxicity. Conclusion: Compared to radiotherapy alone, concomitant chemoradiotherapy is associated with higher rates of severe vaginal and skeletal late toxicities. Other predictive factors include dilator compliance for severe vaginal late toxicity and age for severe vaginal and skeletal late toxicities.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Late Side Effects After Image Guided Intensity Modulated Radiation Therapy Compared to 3D-Conformal Radiation Therapy for Prostate Cancer: Results From 2 Prospective Cohorts

Purpose: Technical developments in the field of external beam radiation therapy (RT) enabled the clinical introduction of image guided intensity modulated radiation therapy (IG-IMRT), which improved target conformity and allowed reduction of safety margins. Whether this had an impact on late toxicity levels compared to previously applied three-dimensional conformal radiation therapy (3D-CRT) is currently unknown. We analyzed late side effects after treatment with IG-IMRT or 3D-CRT, evaluating 2 prospective cohorts of men treated for localized prostate cancer to investigate the hypothesized reductions in toxicity. Methods and Materials: Patients treated with 3D-CRT (n=189) or IG-IMRT (n=242) to 78 Gy in 39 fractions were recruited from 2 Dutch randomized trials with identical toxicity scoring protocols. Late toxicity (>90 days after treatment) was derived from self-assessment questionnaires and case report forms, according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG-EORTC) scoring criteria. Grade ≥2 endpoints included gastrointestinal (GI) rectal bleeding, increased stool frequency, discomfort, rectal incontinence, proctitis, and genitourinary (GU) obstruction, increased urinary frequency, nocturia, urinary incontinence, and dysuria. The Cox proportional hazards regression model was used to compare grade ≥2 toxicities between both techniques, adjusting for other modifying factors. Results: The 5-year cumulative incidence of grade ≥2 GI toxicity was 24.9% for IG-IMRT and 37.6% following 3D-CRT (adjusted hazard ratio [HR]: 0.59, P=.005), with significant reductions in proctitis (HR: 0.37, P=.047) and increased stool frequency (HR: 0.23, P<.001). GU grade ≥2 toxicity levels at 5 years were comparable with 46.2% and 36.4% following IG-IMRT and 3D-CRT, respectively (adjusted HR: 1.19, P=.33). Other strong predictors (P<.01) of grade ≥2 late toxicity were baseline complaints, acute toxicity, and age. Conclusions: Treatment with IG-IMRT reduced the risk of late grade ≥2 complications, whereas GU toxicities remained comparable. This clinically relevant observation demonstrates that IMRT and image-guidance should therefore be the preferred treatment option, provided that margin reduction is implemented with caution.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Cost-Effectiveness Analysis of Stereotactic Body Radiation Therapy Compared With Radiofrequency Ablation for Inoperable Colorectal Liver Metastases

Purpose: To conduct a cost-effectiveness analysis to determine whether stereotactic body radiation therapy (SBRT) is a cost-effective therapy compared with radiofrequency ablation (RFA) for patients with unresectable colorectal cancer (CRC) liver metastases. Methods and Materials: A cost-effectiveness analysis was conducted using a Markov model and 1-month cycle over a lifetime horizon. Transition probabilities, quality of life utilities, and costs associated with SBRT and RFA were captured in the model on the basis of a comprehensive literature review and Medicare reimbursements in 2014. Strategies were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs). To account for model uncertainty, 1-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. Results: In base case analysis, treatment costs for 3 fractions of SBRT and 1 RFA procedure were $13,000 and $4397, respectively. Median survival was assumed the same for both strategies (25 months). The SBRT costs $8202 more than RFA while gaining 0.05 QALYs, resulting in an incremental cost-effectiveness ratio of $164,660 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of median survival from both treatments. Stereotactic body radiation therapy was economically reasonable if better survival was presumed (>1 month gain) or if used for large tumors (>4 cm). Conclusions: If equal survival is assumed, SBRT is not cost-effective compared with RFA for inoperable colorectal liver metastases. However, if better local control leads to small survival gains with SBRT, this strategy becomes cost-effective. Ideally, these results should be confirmed with prospective comparative data.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Comparative life cycle assessment of remote potable water supply for the Department of Defense

The Department of Defense (DOD) and other agencies, including relief organizations, require potable water for remote missions around the globe. As part of recent initiative by the U.S. Federal government through Executive Order 14057, the DOD has been instructed to investigate the sustainability of operations and practices within the context of climate change. One such practice that needs to be addressed is the procurement of potable water, an essential requirement of any remote mission or location. Currently, there are three primary means of procuring potable water at remote locations: bottled water, on-site purification, or tie-in to existing, local infrastructure. The first two operations are often considered the most secure options, but have sustainability concerns. The purpose of this study is to compare the environmental impacts of bottled water procurement versus on-site treatment via a mobile Reverse Osmosis Water Purification Unit (ROWPU), which uses multiple levels of filtration to make potable water from a local source. A cradle-to-gate assessment was developed for both systems to compare different options for potable water supply. An in person inventory was paired with data taken from the Ecoinvent 3.8 database to directly compare the two systems. The two systems are compared on a 5-year timeline to analyze the environmental impact of repeated bottled water transport versus diesel generator-fueled on-site treatment. Across all impact categories, the results indicate that high energy costs of the reverse osmosis process have significantly less impact on the environment than the repetitive transport and procurement of bottled water. The results of the study have important implications for advancing sustainable operations for remote communities or temporary settlements.

54 ENVIRONMENTAL SCIENCES↗

Leaching of indium from obsolete liquid crystal displays: Comparing grinding with electrical disintegration in context of LCA

Highlights: Black-Right-Pointing-Pointer Two pre-treatment methods, prior to leaching of indium from obsolete LCD modules, were described. Black-Right-Pointing-Pointer Conventional grinding and electrical disintegration have been evaluated and compared in the context of LCA. Black-Right-Pointing-Pointer Experimental data on the leaching capacity for indium and the electricity consumption of equipment were inputted into the LCA model in order to compare the environmental performance of each method. Black-Right-Pointing-Pointer An estimate for the environmental performance was calculated as the sum of six impact categories. Black-Right-Pointing-Pointer Electrical disintegration method outperforms conventional grinding in all impact categories. - Abstract: In order to develop an effective recycling system for obsolete Liquid Crystal Displays (LCDs), which would enable both the leaching of indium (In) and the recovery of a pure glass fraction for recycling, an effective liberation or size-reduction method would be an important pre-treatment step. Therefore, in this study, two different types of liberation methods: (1) conventional grinding, and (2) electrical disintegration have been tested and evaluated in the context of Life Cycle Assessment (LCA). In other words, the above-mentioned methods were compared in order to find out the one that ensures the highest leaching capacity for indium, as well as the lowest environmental burden. One of the main findings of this study was that the electrical disintegration was the most effective liberation method, since it fully liberated the indium containing-layer, ensuring a leaching capacity of 968.5 mg-In/kg-LCD. In turn, the estimate for the environmental burden was approximately five times smaller when compared with the conventional grinding.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Implications of sustainable development considerations for comparability across nationally determined contributions

An important component of analyses of the Paris Agreement has been the assessment of comparability of countries’ nationally determined contributions (NDCs). These assessments have typically focused on a set of emissions or cost-based indicators1-8. At the same time, an increasing body of literature is articulating many possible linkages between mitigation and other national priorities, with a major focus on the Sustainable Development Goals (SDGs)9-13. The importance of the SDGs raises a question about how their linkages to mitigation activities might influence comparability assessments. We explore this question using a global integrated assessment model14 and provide illustrations of the geographical distributions of the influence of the NDCs on broader sustainability goals. We demonstrate that the extent to which these distributions differ from the distribution of mitigation effort obtained using standard comparability metrics depends on the degree to which domestic mitigation actions affect broader sustainability goals domestically and/or internationally and whether these effects are synergistic or antagonistic. Our analysis provides a foundation for considering how comparability across the NDCs could be better understood in the larger context of sustainability.

Iyer, Gokul (ORCID:0000000235657526)↗

Comparative study of electrical breakdown properties of deionized water and heavy water under pulsed power conditions

A comparative study of electrical breakdown properties of deionized water (H{sub 2}O) and heavy water (D{sub 2}O) is presented with two different electrode materials (stainless steel (SS) and brass) and polarity (positive and negative) combinations. The pulsed (∼a few tens of nanoseconds) discharges are conducted by applying high voltage (∼a few hundred kV) pulse between two hemisphere electrodes of the same material, spaced 3 mm apart, at room temperature (∼26-28 °C) with the help of Tesla based pulse generator. It is observed that breakdown occurred in heavy water at lesser voltage and in short duration compared to deionized water irrespective of the electrode material and applied voltage polarity chosen. SS electrodes are seen to perform better in terms of the voltage withstanding capacity of the liquid dielectric as compared to brass electrodes. Further, discharges with negative polarity are found to give slightly enhanced discharge breakdown voltage when compared with those with positive polarity. The observations corroborate well with conductivity measurements carried out on original and post-treated liquid samples. An interpretation of the observations is attempted using Fourier transform infrared measurements on original and post-treated liquids as well as in situ emission spectra studies. A yet another important observation from the emission spectra has been that even short (nanosecond) duration discharges result in the formation of a considerable amount of ions injected into the liquid from the electrodes in a similar manner as reported for long (microseconds) discharges. The experimental observations show that deionised water is better suited for high voltage applications and also offer a comparison of the discharge behaviour with different electrodes and polarities.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Comparing ICME simulations with scaled laboratory experiment

In stellar physics and astrophysics, numerical simulations and laboratory experiments are often compared to observational data to support their representation of the real world. However, there is also merit in comparing numerical simulations to properly scaled experiments, especially when the experiment and the simulation are both emulating the solar phenomena. Confirming the credibility of scaled experiments and their scaling with well-validated models is important to expand our knowledge of the associated physical phenomena. This is significant because experiments and simulations can be performed frequently, whereas observations may be limited by location, field of view, and missing data. In this work, we use the Alfvén Wave Solar atmosphere Model, a well-validated magnetohydrodynamic model, to simulate an interplanetary coronal mass ejection (ICME) and compare it to an experiment which provides a scaled analog to a physical ICME. The experiment was performed on the Big Red Ball facility and scaled using dimensionless parameters such as plasma β and magnetosonic Mach number to reproduce the main structure of an ICME. We compare the model-simulated temperature, density, and magnetic field to those from the experiment, as well as the scaling parameters used in the experiment, to those calculated from the simulation. This comparison is performed to further justify the scaling arguments made by the experiment. Additionally, the comparison would lead to the development of stronger scaling arguments for future experiments.

Bryant, K. [University of Michigan, Ann Arbor, MI ↗

Model-based data center cooling controls comparative co-design

This article presents a comparative simulation-based control logic design process. It uses the Control Description Language (CDL) and the ASHRAE Guideline 36 high-performing building control sequences with the Modelica Buildings Library (MBL) to demonstrate a comparative analysis of two control designs for a data center chilled water plant. Details include a description of the closed-loop plant and control design methodology, including sizing and parameterization, base and alternative (Guideline 36) control logic with software implementation structure, and outline of the simulation experimentation process. The selected control designs are paired with comparable chilled water plant configurations. The models include a chiller, a water-side economizer, and an evaporative cooling tower. The plant provides cooling at 27ºC zone supply air temperature to a data center in Sacramento, CA. The comparative simulation results examined the impacts of a selected control logic detail, and present an example model-based design application. Overall, the simulation results showed a 25% annual and a 18% summer energy use reduction for alternative controls. This shows that simulation-based control logic design performance evaluation can improve energy efficiency and resilience aspects of system controls at large.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

A Software Framework for Comparing Training Approaches for Spiking Neuromorphic Systems

There are a wide variety of training approaches for spiking neural networks for neuromorphic deployment. However, it is often not clear how these training algorithms perform or compare when applied across multiple neuromorphic hardware platforms and multiple datasets. In this work, we present a software framework for comparing performance across four neuromorphic training algorithms across three neuromorphic simulators and four simple classification tasks. We introduce an approach for training a spiking neural network using a decision tree, and we compare this approach to training algorithms based on evolutionary algorithms, back-propagation, and reservoir computing. We present a hyperparameter optimization approach to tune the hyperparameters of the algorithm, and show that these optimized hyperparameters depend on the processor, algorithm, and classification task. Finally, we compare the performance of the optimized algorithms across multiple metrics, including accuracy, training time, and resulting network size, and we show that there is not one best training algorithm across all datasets and performance metrics.

Schuman, Catherine↗

Top-Performing Photovoltaic Cells Compared to the Shockley–Queisser Limit

Top-performing single-junction and two-terminal tandem devices that include at least one polycrystalline cell are compared with each other and their ideal limits. The parameters of open-circuit voltage, short-circuit current, and fill-factor are individually compared to the Shockley–Queisser limit to investigate where different technologies have room to improve. Technologies, such as silicon and cadmium telluride have the most room for improvement in open-circuit voltage currently utilizing 87% and 81% of their maxima, respectively. Detailed diode and fill-factor loss analysis is presented for single-junction devices to give further insight on how they compare and where efficiency is lost. Single-crystal technologies demonstrate a fill-factor closer to the Shockley–Queisser limit than polycrystalline devices. The high diode quality factor of polycrystalline devices is the leading cause of the decreased fill-factor. Similar analysis on tandem cells with at least one thin-film cell shows that although their efficiency exceeds that of the single-junction cells, the fraction of their ideal efficiency is smaller. Here, by comparing parameters to the Shockley–Queisser limit, it becomes clearer where certain technologies have the potential for improvement.

High efficiency↗

Reduced peripheral activity leading to hepato‐preferential action of basal insulin peglispro compared with insulin glargine in patients with type 1 diabetes

Aims Basal insulin peglispro ( BIL ), a novel PEGylated basal insulin with a large hydrodynamic size, has a delayed absorption and reduced clearance that prolongs the duration of action. The current study compared the effects of BIL and insulin glargine ( GL ) on endogenous glucose production ( EGP ), glucose disposal rate ( GDR ) and lipolysis in patients with type 1 diabetes. Materials and Methods This was a randomized, open‐label, four‐period, crossover study. Patients received intravenous infusions of BIL and GL , each at two dose levels selected for partial and maximal suppression of EGP , during an 8 to 10 h euglycemic clamp procedure with d ‐[3‐ 3 H] glucose. Results Following correction for equivalent human insulin concentrations ( EHIC ), low‐dose GL infusion resulted in similar EGP at the end of the clamp compared to low‐dose BIL infusion ( GL / BIL ratio of 1.03) but a higher GDR ( GL / BIL ratio of 2.42), indicating similar hepatic activity but attenuated peripheral activity of BIL . Consistent with this, the EHIC ‐corrected GDR / EGP at the end of the clamp was 1.72‐fold greater for GL than BIL following low‐dose administration. At the lower dose of BIL and GL (concentrations in the therapeutic range), BIL produced less suppression of lipolysis compared with GL as indicated by free fatty acid and glycerol levels at the end of the clamp. Conclusions Compared with GL , BIL restored the hepato‐peripheral insulin action gradient seen in normal physiology via its peripherally restricted action on target tissues related to carbohydrate and lipid metabolism.

Mudaliar, S.↗

Continental Scale Hydrostratigraphy: Comparing Geologically Informed Data Products to Analytical Solutions

Abstract This study synthesizes two different methods for estimating hydraulic conductivity (K) at large scales. We derive analytical approaches that estimate K and apply them to the contiguous United States. We then compare these analytical approaches to three‐dimensional, national gridded K data products and three transmissivity (T) data products developed from publicly available sources. We evaluate these data products using multiple approaches: comparing their statistics qualitatively and quantitatively and with hydrologic model simulations. Some of these datasets were used as inputs for an integrated hydrologic model of the Upper Colorado River Basin and the comparison of the results with observations was used to further evaluate the K data products. Simulated average daily streamflow was compared to daily flow data from 10 USGS stream gages in the domain, and annually averaged simulated groundwater depths are compared to observations from nearly 2000 monitoring wells. We find streamflow predictions from analytically informed simulations to be similar in relative bias and Spearman's rho to the geologically informed simulations. R ‐squared values for groundwater depth predictions are close between the best performing analytically and geologically informed simulations at 0.68 and 0.70 respectively, with RMSE values under 10 m. We also show that the analytical approach derived by this study produces estimates of K that are similar in spatial distribution, standard deviation, mean value, and modeling performance to geologically‐informed estimates. The results of this work are used to inform a follow‐on study that tests additional data‐driven approaches in multiple basins within the contiguous United States.

54 ENVIRONMENTAL SCIENCES↗

A comparative study of small field total scatter factors and dose profiles using plastic scintillation detectors and other stereotactic dosimeters: The case of the CyberKnife

Purpose: Small-field dosimetry is challenging, and the main limitations of most dosimeters are insufficient spatial resolution, water nonequivalence, and energy dependence. The purpose of this study was to compare plastic scintillation detectors (PSDs) to several commercial stereotactic dosimeters by measuring total scatter factors and dose profiles on a CyberKnife system. Methods: Two PSDs were developed, having sensitive volumes of 0.196 and 0.785 mm{sup 3}, and compared with other detectors. The spectral discrimination method was applied to subtract Cerenkov light from the signal. Both PSDs were compared to four commercial stereotactic dosimeters by measuring total scatter factors, namely, an IBA dosimetry stereotactic field diode (SFD), a PTW 60008 silicon diode, a PTW 60012 silicon diode, and a microLion. The measured total scatter factors were further compared with those of two independent Monte Carlo studies. For the dose profiles, two commercial detectors were used for the comparison, i.e., a PTW 60012 silicon diode and Gafchromics EBT2. Total scatter factors for a CyberKnife system were measured in circular fields with diameters from 5 to 60 mm. Dose profiles were measured for the 5- and 60-mm cones. The measurements were performed in a water tank at a 1.5-cm depth and an 80-cm source-axis distance. Results: The total scatter factors measured using all the detectors agreed within 1% with the Monte Carlo values for cones of 20 mm or greater in diameter. For cones of 10-20 mm in diameter, the PTW 60008 silicon diode was the only dosimeter whose measurements did not agree within 1% with the Monte Carlo values. For smaller fields (<10 mm), each dosimeter type showed different behaviors. The silicon diodes over-responded because of their water nonequivalence; the microLion and 1.0-mm PSD under-responded because of a volume-averaging effect; and the 0.5-mm PSD was the only detector within the uncertainties of the Monte Carlo simulations for all the cones. The PSDs, the PTW 60012 silicon diode, and the Gafchromics EBT2 agreed within 2% and 0.2 mm (gamma evaluation) for the measured dose profiles except in the tail of the 60-mm cone. Conclusions: Silicon diodes can be used to accurately measure small-field dose profiles but not to measure total scatter factors, whereas PSDs can be used to accurately measure both. The authors' measurements show that the use of a 1.0-mm PSD resulted in a negligible volume-averaging effect (under-response of Almost-Equal-To 1%) down to a field size of 5 mm. Therefore, PSDs are strong candidates to become reference radiosurgery detectors for beam characterization and quality assurance measurements.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Climate Change Projections in CESM1(CAM5) Compared to CCSM4

Future climate change projections for phase 5 of the Coupled Model Intercomparison Project (CMIP5) are introduced for the Community Earth System Model version 1 that includes the Community Atmospheric Model version 5 [CESM1(CAM5)]. These findings are compared to the Community Climate System Model, version 4 (CCSM4) and include simulations using the representative concentration pathway (RCP) mitigation scenarios, and extensions for those scenarios beyond 2100 to 2300. Equilibrium climate sensitivity of CESM1(CAM5) is 4.10°C, which is higher than the CCSM4 value of 3.20°C. The transient climate response is 2.33°C, compared to the CCSM4 value of 1.73°C. Thus, even though CESM1(CAM5) includes both the direct and indirect effects of aerosols (CCSM4 had only the direct effect), the overall climate system response including forcing and feedbacks is greater in CESM1(CAM5) compared to CCSM4. The Atlantic Ocean meridional overturning circulation (AMOC) in CESM1(CAM5) weakens considerably in the twenty-first century in all the RCP scenarios, and recovers more slowly in the lower forcing scenarios. The total aerosol optical depth (AOD) changes from ~0.12 in 2006 to ~0.10 in 2100, compared to a preindustrial 1850 value of 0.08, so there is less negative forcing (a net positive forcing) from that source during the twenty-first century. As a result, the change from 2006 to 2100 in aerosol direct forcing in CESM1(CAM5) contributes to greater twenty-first century warming relative to CCSM4. There is greater Arctic warming and sea ice loss in CESM1(CAM5), with an ice-free summer Arctic occurring by about 2060 in RCP8.5 (2040s in September) as opposed to about 2100 in CCSM4 (2060s in September).

54 ENVIRONMENTAL SCIENCES↗

How Time Inefficient and Uncertain are Paratransit Trips Compared to Car Trips

The Americans with Disabilities Act (ADA) stipulates that paratransit mobility be comparable to public transit. However, with just under 5% of the population relying on public transportation, transit is not a representative benchmark. To highlight this inequality, we compare trip times by paratransit to counterfactual car-based travel. Using 2.5 years of demand data from the Denver Regional Transportation District's Access-a-Ride service, we compare paratransit trip times to counterfactual car-based trips for the same origin-destination pairs, controlling for various trip characteristics. Compared to car travel, the findings indicate high variability and uncertainty associated with paratransit trip times. For the same origin-destination pairs, the mean paratransit trip time is almost twice that of the mean car travel time, with a standard deviation for paratransit trip time fourfold that of the standard deviation for car trip time. For perspective, traveling an average of 10 mi during the 7-8 a.m. morning peak can take about 16 min by car with almost no variability, while that same trip can take an average of 25 min by paratransit, with 5% of trips being outside the 95% confidence interval and thus unpredictable. Paratransit trip time inefficiency tends to be particularly worse for females; older adults; those making trips between 9 and 11 a.m.; cash-paying customers; those making shorter trips; and those traveling during inclement weather, including cold temperatures. These findings suggest a need to re-assess using public transit as a benchmark for paratransit supply as regulated by the ADA.

accessible transportation and mobility↗

Comparative genomic analysis of single-molecule sequencing and hybrid approaches for finishing the Clostridium autoethanogenum JA1-1 strain DSM 10061 genome

Background Clostridium autoethanogenum strain JA1-1 (DSM 10061) is an acetogen capable of fermenting CO, CO2 and H2 (e.g. from syngas or waste gases) into biofuel ethanol and commodity chemicals such as 2,3-butanediol. A draft genome sequence consisting of 100 contigs has been published. Results A closed, high-quality genome sequence for C. autoethanogenum DSM10061 was generated using only the latest single-molecule DNA sequencing technology and without the need for manual finishing. It is assigned to the most complex genome classification based upon genome features such as repeats, prophage, nine copies of the rRNA gene operons. It has a low G + C content of 31.1%. Illumina, 454, Illumina/454 hybrid assemblies were generated and then compared to the draft and PacBio assemblies using summary statistics, CGAL, QUAST and REAPR bioinformatics tools and comparative genomic approaches. Assemblies based upon shorter read DNA technologies were confounded by the large number repeats and their size, which in the case of the rRNA gene operons were ~5 kb. CRISPR (Clustered Regularly Interspaced Short Paloindromic Repeats) systems among biotechnologically relevant Clostridia were classified and related to plasmid content and prophages. Potential associations between plasmid content and CRISPR systems may have implications for historical industrial scale Acetone-Butanol-Ethanol (ABE) fermentation failures and future large scale bacterial fermentations. While C. autoethanogenum contains an active CRISPR system, no such system is present in the closely related Clostridium ljungdahlii DSM 13528. A common prophage inserted into the Arg-tRNA shared between the strains suggests a common ancestor. However, C. ljungdahlii contains several additional putative prophages and it has more than double the amount of prophage DNA compared to C. autoethanogenum. Other differences include important metabolic genes for central metabolism (as an additional hydrogenase and the absence of a phophoenolpyruvate synthase) and substrate utilization pathway (mannose and aromatics utilization) that might explain phenotypic differences between C. autoethanogenum and C. ljungdahlii. Conclusions Single molecule sequencing will be increasingly used to produce finished microbial genomes. The complete genome will facilitate comparative genomics and functional genomics and support future comparisons between Clostridia and studies that examine the evolution of plasmids, bacteriophage and CRISPR systems.

BESC↗

Genetic analysis of inflorescence and plant height components in sorghum (Panicoidae) and comparative genetics with rice (Oryzoidae)

Domestication has played an important role in shaping characteristics of the inflorescence and plant height in cultivated cereals. Taking advantage of meta-analysis of QTLs, phylogenetic analyses in 502 diverse sorghum accessions, GWAS in a sorghum association panel (n = 354) and comparative data, we provide insight into the genetic basis of the domestication traits in sorghum and rice. We performed genome-wide association studies (GWAS) on 6 traits related to inflorescence morphology and 6 traits related to plant height in sorghum, comparing the genomic regions implicated in these traits by GWAS and QTL mapping, respectively. In a search for signatures of selection, we identify genomic regions that may contribute to sorghum domestication regarding plant height, flowering time and pericarp color. Comparative studies across taxa show functionally conserved ‘hotspots’ in sorghum and rice for awn presence and pericarp color that do not appear to reflect corresponding single genes but may indicate co-regulated clusters of genes. We also reveal homoeologous regions retaining similar functions for plant height and flowering time since genome duplication an estimated 70 million years ago or more in a common ancestor of cereals. In most such homoeologous QTL pairs, only one QTL interval exhibits strong selection signals in modern sorghum. Intersections among QTL, GWAS and comparative data advance knowledge of genetic determinants of inflorescence and plant height components in sorghum, and add new dimensions to comparisons between sorghum and rice.

09 BIOMASS FUELS↗