Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “regression analysis”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36

Characterization of energy response for photon-counting detectors using x-ray fluorescence

Purpose: To investigate the feasibility of characterizing a Si strip photon-counting detector using x-ray fluorescence. Methods: X-ray fluorescence was generated by using a pencil beam from a tungsten anode x-ray tube with 2 mm Al filtration. Spectra were acquired at 90° from the primary beam direction with an energy-resolved photon-counting detector based on an edge illuminated Si strip detector. The distances from the source to target and the target to detector were approximately 19 and 11 cm, respectively. Four different materials, containing silver (Ag), iodine (I), barium (Ba), and gadolinium (Gd), were placed in small plastic containers with a diameter of approximately 0.7 cm for x-ray fluorescence measurements. Linear regression analysis was performed to derive the gain and offset values for the correlation between the measured fluorescence peak center and the known fluorescence energies. The energy resolutions and charge-sharing fractions were also obtained from analytical fittings of the recorded fluorescence spectra. An analytical model, which employed four parameters that can be determined from the fluorescence calibration, was used to estimate the detector response function. Results: Strong fluorescence signals of all four target materials were recorded with the investigated geometry for the Si strip detector. The average gain and offset of all pixels for detector energy calibration were determined to be 6.95 mV/keV and −66.33 mV, respectively. The detector’s energy resolution remained at approximately 2.7 keV for low energies, and increased slightly at 45 keV. The average charge-sharing fraction was estimated to be 36% within the investigated energy range of 20–45 keV. The simulated detector output based on the proposed response function agreed well with the experimental measurement. Conclusions: The performance of a spectral imaging system using energy-resolved photon-counting detectors is very dependent on the energy calibration of the detector. The proposed x-ray fluorescence technique offers an accurate and efficient way to calibrate the energy response of a photon-counting detector.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Attenuation-based size metric for estimating organ dose to patients undergoing tube current modulated CT exams

Purpose: Task Group 204 introduced effective diameter (ED) as the patient size metric used to correlate size-specific-dose-estimates. However, this size metric fails to account for patient attenuation properties and has been suggested to be replaced by an attenuation-based size metric, water equivalent diameter (D{sub W}). The purpose of this study is to investigate different size metrics, effective diameter, and water equivalent diameter, in combination with regional descriptions of scanner output to establish the most appropriate size metric to be used as a predictor for organ dose in tube current modulated CT exams. Methods: 101 thoracic and 82 abdomen/pelvis scans from clinically indicated CT exams were collected retrospectively from a multidetector row CT (Sensation 64, Siemens Healthcare) with Institutional Review Board approval to generate voxelized patient models. Fully irradiated organs (lung and breasts in thoracic scans and liver, kidneys, and spleen in abdominal scans) were segmented and used as tally regions in Monte Carlo simulations for reporting organ dose. Along with image data, raw projection data were collected to obtain tube current information for simulating tube current modulation scans using Monte Carlo methods. Additionally, previously described patient size metrics [ED, D{sub W}, and approximated water equivalent diameter (D{sub Wa})] were calculated for each patient and reported in three different ways: a single value averaged over the entire scan, a single value averaged over the region of interest, and a single value from a location in the middle of the scan volume. Organ doses were normalized by an appropriate mAs weighted CTDI{sub vol} to reflect regional variation of tube current. Linear regression analysis was used to evaluate the correlations between normalized organ doses and each size metric. Results: For the abdominal organs, the correlations between normalized organ dose and size metric were overall slightly higher for all three differently (global, regional, and middle slice) reported D{sub W} and D{sub Wa} than they were for ED, but the differences were not statistically significant. However, for lung dose, computed correlations using water equivalent diameter calculated in the middle of the image data (D{sub W,middle}) and averaged over the low attenuating region of lung (D{sub W,regional}) were statistically significantly higher than correlations of normalized lung dose with ED. Conclusions: To conclude, effective diameter and water equivalent diameter are very similar in abdominal regions; however, their difference becomes noticeable in lungs. Water equivalent diameter, specifically reported as a regional average and middle of scan volume, was shown to be better predictors of lung dose. Therefore, an attenuation-based size metric (water equivalent diameter) is recommended because it is more robust across different anatomic regions. Additionally, it was observed that the regional size metric reported as a single value averaged over a region of interest and the size metric calculated from a single slice/image chosen from the middle of the scan volume are highly correlated for these specific patient models and scan types.

60 APPLIED LIFE SCIENCES↗

The proton charge radius extracted from the initial-state radiation experiment at MAMI

Abstract We report on a comprehensive reinterpretation of the existing cross-section data for elastic electron-proton scattering obtained by the initial-state radiation technique, resulting in a significantly improved accuracy of the extracted proton charge radius. By refining the external energy corrections we have achieved an outstanding description of the radiative tail, essential for a detailed investigation of the proton finite-size effects on the measured cross sections. This development, together with a novel framework for determining the radius, based on a regression analysis of the cross sections employing a polynomial model for the form factor, led us to a new value for the charge radius, which is $$(0.878 \pm 0.011_\mathrm {stat.}\pm 0.031_\mathrm {sys.}\pm 0.002_\mathrm {mod.})\,\mathrm {fm}$$ ( 0.878 ± 0 . 011 stat . ± 0 . 031 sys . ± 0 . 002 mod . ) fm

Physics↗

An Adaptive Cross-Architecture Combination Method for Graph Traversal

Breadth-First Search (BFS) is widely used in many real-world applications including computational biology, social networks, and electronic design automation. The combination method, using both top-down and bottom-up techniques, is the most effective BFS approach. However, current combination methods rely on trial-and-error and exhaustive search to locate the optimal switching point, which may cause significant runtime overhead. To solve this problem, we design an adaptive method based on regression analysis to predict an optimal switching point for the combination method at runtime within less than 0.1% of the BFS execution time.

You, Yang↗

Composition and Manufacturing Effects on Electrical Conductivity of Li/FeS 2 Thermal Battery Cathodes

The electrical conductivity is key to the performance of thermal battery cathodes. In this work we present the effects of manufacturing and processing conditions on the electrical conductivity of Li/FeS2 thermal battery cathodes. Finite element simulations were used to compute the conductivity of three-dimensional microcomputed tomography cathode microstructures and compare results to experimental impedance spectroscopy measurements. A regression analysis reveals a predictive relationship between composition, processing conditions, and electrical conductivity; a trend which is largely erased after thermally-induced deformation. Moreover, the trend applies to both experimental and simulation results, although is not as apparent in simulations. This research is a step toward a more fundamental understanding of the effects of processing and composition on thermal battery component microstructure, properties, and performance.

25 ENERGY STORAGE↗

Association Between Prevalence of Peripheral Artery Disease and Radiation Exposure in the Atomic Bomb Survivors

Past reports suggested that total-body irradiation at 0.5 to 1.0 Gy could be responsible for atherosclerosis. Peripheral artery disease (PAD) is a manifestation of systematic atherosclerosis. Whether the consequences of a low-to-moderate dose of radiation include increased risk of PAD remains to be determined. The purpose of this study was to examine the association between radiation exposure and prevalence of PAD among Japanese atomic bomb survivors. Radiation exposure from the atomic bombing was assessed in 3476 participants (41.1% men, mean age 74.8 years with SD 6.4 years) with a cross-sectional survey in 2010 to 2014. Left- and right-side ankle-brachial indexes and upstroke time (UT) were obtained using oscillometric VP-2000. PAD was defined as an ankle-brachial index of 1.0 or less or a prior history related to revascularization. UT was considered a sensitive marker of early-stage PAD. Association between radiation exposure and PAD or UT was assessed using multivariable regression analyses with adjustment for potential confounding factors. Of 3476 participants, 79 (2.3%) were identified as having prevalent PAD. Multivariate logistic regression analysis indicated that radiation dose was unrelated to PAD prevalence (odds ratio, 0.83; 95% confidence interval [0.57-1.21]). UT appeared to increase with radiation dose, but the increase was not statistically significant (1.09 ms/Gy; 95% confidence interval [-0.17 to 2.36]). We found no clear association of radiation dose with PAD, but it remains to be determined whether UT is associated with radiation dose.

60 APPLIED LIFE SCIENCES↗

Two-Day Westward-Propagating Inertio-Gravity Waves during GoAmazon

The dynamical and thermodynamical features of Amazonian 2-day westward-propagating inertia–gravity (WIG) waves are examined. On the basis of a linear regression analysis of satellite brightness temperature and data from the 2014–15 Observations and Modeling of the Green Ocean Amazon (GoAmazon) field campaign, it is shown that Amazonian WIG waves exhibit structure and propagation characteristics consistent with the n = 1 WIG waves from shallow water theory. These WIG waves exhibit a pronounced seasonality, with peak activity occurring from March to May and a minimum occurring from June to September. Evidence is shown that mesoscale convective systems over the Amazon are frequently organized in 2-day WIG waves. Results suggest that many of the Amazonian WIG waves come from preexisting 2-day waves over the Atlantic, which slow down when coupled with the deeper, more intense convection over tropical South America. In contrast to WIG waves that occur over the ocean, Amazonian 2-day WIG waves exhibit a pronounced signature in surface temperature, moisture, and heat fluxes.

54 ENVIRONMENTAL SCIENCES↗

Biogeophysical Effects of Land-Use and Land-Cover Change Not Detectable in Warmest Month

Land-use and land-cover changes (hereafter simply “land use”) alter climates biogeophysically by affecting surface fluxes of energy and water. Yet, near-surface temperature responses to land use across observational versus model-based studies and spatial-temporal scales can be inconsistent. Here we assess the prevalence of the historical land use signal of daily maximum temperatures averaged over the warmest month of the year (t LU ) using regularized optimal fingerprinting for detection and attribution. We use observations from the Climatic Research Unit and Berkeley Earth alongside historical simulations with and without land use from phase 6 of the Coupled Model Intercomparison Project to reconstruct an experiment representing the effects of land use on climate. To assess the signal of land use at spatially resolved continental and global scales, we aggregate all input data across reference regions and continents, respectively. At both scales, land use does not comprise a significantly detectable set of forcings for two of four Earth system models and their multimodel mean. Furthermore, using a principal component analysis, we find that t LU is mostly composed of the nonlocal effects of land use rather than its local effects. These findings show that, at scales relevant for climate attribution, uncertainties in Earth system model representations of land use are too high relative to the effects of internal variability to confidently assess land use.

54 ENVIRONMENTAL SCIENCES↗

Differential patterns of reproductive and lifestyle risk factors for breast cancer according to birth cohorts among women in China, Japan and Korea

Background: The birth cohort effect has been suggested to influence the rate of breast cancer incidence and the trends of associated reproductive and lifestyle factors. We conducted a cohort study to determine whether a differential pattern of associations exists between certain factors and breast cancer risk based on birth cohorts. Methods: This was a cohort study using pooled data from 12 cohort studies. We analysed associations between reproductive (menarche age, menopause age, parity and age at first delivery) and lifestyle (smoking and alcohol consumption) factors and breast cancer risk. We obtained hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard regression analysis on the 1920s, 1930s, 1940s and 1950s birth cohorts. Results: Parity was found to lower the risk of breast cancer in the older but not in the younger birth cohort, whereas lifestyle factors showed associations with breast cancer risk only among the participants born in the 1950s. In the younger birth cohort group, the effect size was lower for parous women compared to the other cohort groups (HR [95% CI] 0.86 [0.66–1.13] compared to 0.60 [0.49–0.73], 0.46 [0.38–0.56] and 0.62 [0.51–0.77]). Meanwhile, a higher effect size was found for smoking (1.45 [1.14–1.84] compared to 1.25 [0.99–1.58], 1.06 [0.85–1.32] and 0.86 [0.69–1.08]) and alcohol consumption (1.22 [1.01–1.48] compared to 1.10 [0.90–1.33], 1.15 [0.96–1.38], and 1.07 [0.91–1.26]). Conclusion: We observed different associations of parity, smoking and alcohol consumption with breast cancer risk across various birth cohorts.

60 APPLIED LIFE SCIENCES↗

Evaluation of an open forecasting challenge to assess skill of West Nile virus neuroinvasive disease prediction

Abstract Background West Nile virus (WNV) is the leading cause of mosquito-borne illness in the continental USA. WNV occurrence has high spatiotemporal variation, and current approaches to targeted control of the virus are limited, making forecasting a public health priority. However, little research has been done to compare strengths and weaknesses of WNV disease forecasting approaches on the national scale. We used forecasts submitted to the 2020 WNV Forecasting Challenge, an open challenge organized by the Centers for Disease Control and Prevention, to assess the status of WNV neuroinvasive disease (WNND) prediction and identify avenues for improvement. Methods We performed a multi-model comparative assessment of probabilistic forecasts submitted by 15 teams for annual WNND cases in US counties for 2020 and assessed forecast accuracy, calibration, and discriminatory power. In the evaluation, we included forecasts produced by comparison models of varying complexity as benchmarks of forecast performance. We also used regression analysis to identify modeling approaches and contextual factors that were associated with forecast skill. Results Simple models based on historical WNND cases generally scored better than more complex models and combined higher discriminatory power with better calibration of uncertainty. Forecast skill improved across updated forecast submissions submitted during the 2020 season. Among models using additional data, inclusion of climate or human demographic data was associated with higher skill, while inclusion of mosquito or land use data was associated with lower skill. We also identified population size, extreme minimum winter temperature, and interannual variation in WNND cases as county-level characteristics associated with variation in forecast skill. Conclusions Historical WNND cases were strong predictors of future cases with minimal increase in skill achieved by models that included other factors. Although opportunities might exist to specifically improve predictions for areas with large populations and low or high winter temperatures, areas with high case-count variability are intrinsically more difficult to predict. Also, the prediction of outbreaks, which are outliers relative to typical case numbers, remains difficult. Further improvements to prediction could be obtained with improved calibration of forecast uncertainty and access to real-time data streams (e.g. current weather and preliminary human cases). Graphical Abstract

54 ENVIRONMENTAL SCIENCES↗

A numerical study of surface-wave-based tunnel detection at the Black Diamond Mines Regional Preserve, California

Detecting underground voids, such as old mine workings, solution cavities in karst terrain, or unknown tunnels such as illicit cross-border tunnels, is a challenging problem for geophysics and an important concern for geotechnical design, public safety, and domestic security. Seismic surface-wave-based detection methods have become increasingly popular for detecting relatively shallow and small targets; however, the theoretical limitations of these methods have thus far remained unclear. We use a suite of 3D numerical simulations inspired by a tunnel detection experiment carried out at the Black Diamond Mines Regional Preserve (BDM) in northern California. The geophysical anomalies predicted by our numerical simulations at BDM agree with field observations, and our estimates for the location of the primary tunnel target agree with historical records in the area. Using our calibrated numerical model, we perform a parametric study to determine the effect of tunnel size, depth of burial, filling material, and source characteristics to determine the range over which surface-wave backscattering and attenuation-based methods are effective. Additionally, we perform a regression analysis to determine a relationship for the maximum depth at which a tunnel may be detected via these approaches, given the target diameter, wavelength of interest, and the signal-to-noise ratio.

58 GEOSCIENCES↗

Internal Mammary Chain Sentinel Nodes in Early-Stage Breast Cancer Patients: Toward Selective Removal

Background: Removal of internal mammary chain sentinel nodes (IMCSNs) affects prognosis and treatment of breast cancer, and internal mammary chain radiotherapy (IMCRT) can improve survival for selected patients. This study aimed to determine the effect of IMCSN biopsy on recurrence-free survival (RFS) and overall survival (OS) and to identify predictive factors for IMCSN and distant metastasis. Methods: Patients with IMCSNs were selected from a prospective database for the period 1999–2007. Lymphoscintigraphy was performed after intratumoral technetium-99 m injection, and all sentinel nodes were removed. Both RFS and OS were calculated for subgroups with tumor-positive, tumor-negative, or non-removed IMCSNs. Predictive factors were identified for tumor-positive IMCSNs and distant metastasis by regression analysis. Results: For 287 (85%) of 336 patients, IMCSN biopsy was performed, and metastasis was detected in 38 patients (13%). The patients with tumor-positive IMCSNs had poorer OS than the patients with no IMCSN metastasis or non-removed IMCSNs (p = 0.002). These patients also had worse RFS due to distant metastasis (p = 0.002). Axillary metastasis was predictive for tumor-positive IMCSNs (positive predictive value, 38.5%). The predictive factors for distant metastasis were tumor-positive IMCSNs (hazard ratio [HR], 2.5), non-removed IMCSNs (HR, 2.3), tumor diameter greater than 1.5 cm (HR, 3.5), and age older than 65 years (HR, 3.1; reference, < 50 years). Conclusions: Patients with IMCSNs have worse survival due to distant metastasis. The clinically relevant predictive factor for distant metastasis is tumor larger than 1.5 cm. According to the authors’ current protocol, IMCSN biopsy is performed for patients younger than 70 years who have a tumor larger than 1.5 cm, with the cardiotoxicity of the adjuvant IMCRT weighed against the survival benefit.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Tumor Volume Is Better Than Diameter for Predicting the Prognosis of Patients with Early-Stage Non-small Cell Lung Cancer

Background: This study aimed to investigate whether tumor volume (TV) is better than diameter for predicting the prognosis of patients with early-stage non-small cell lung cancer (NSCLC) after complete resection. Methods: This study retrospectively reviewed the clinicopathologic characteristics of 274 patients with early-stage NSCLC who had received pretreatment computed tomography (CT) scans and complete resection. TV was semi-automatically measured from CT scans using an imaging software program. The optimal cutoff of TV was determined by X-tile software. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan–Meier method. The prognostic significance of TV and other variables was assessed by Cox proportional hazards regression analysis. Results: Using 3.046 cm{sup 3} and 8.078 cm{sup 3} as optimal cutoff values of TV, the patients were separated into three groups. A larger TV was significantly associated with poor DFS and OS in the multivariable analysis. Kaplan–Meier curves of DFS and OS showed significant differences on the basis of TV among patients with stage 1a disease, greatest tumor diameter (GTD) of 2 cm or smaller, and GTD of 2–3 cm, respectively. Using two TV cutoff points, three categories of TV were created. In 54 cases (19.7%), patients migrated from the GTD categories of 2 cm or smaller, 2–3 cm, and larger than 3 cm into the TV categories of 3.046 cm{sup 3} or smaller, 3.046–8.078 cm{sup 3}, and larger than 8.078 cm{sup 3}. Conclusion: TV is an independent prognostic factor of DFS and OS for early-stage NSCLC. The findings show that TV is better than GTD for predicting the prognosis of patients with early-stage NSCLC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Perioperative Use of Nonsteroidal Anti-inflammatory Drugs Decreases the Risk of Recurrence of Cancer After Colorectal Resection: A Cohort Study Based on Prospective Data

Background: Perioperative use of nonsteroidal anti-inflammatory drugs (NSAIDs) is known to reduce inflammatory response in relation to surgery. Inflammation may promote recurrence of cancer, thus inhibition by use of NSAIDs could reduce recurrence after surgery. Objective: The aim of this study was to examine the association between perioperative use of NSAIDs and cancer recurrence, as well as disease-free survival (DFS) and mortality after colorectal cancer surgery. Methods: This was a cohort study based on data from a prospective clinical database, electronic medical records, and nationwide registers, and included patients from six major colorectal centers in Denmark. The primary outcome was cancer recurrence, while secondary outcomes included 5-year mortality and DFS. Results: Overall, 2308 patients undergoing colorectal cancer surgery between 1 January 2006 and 31 December 2009 were included. A total of 909 patients received at least 2 days of treatment with NSAIDs, of whom 702 (77.2%) received ibuprofen and 204 (22.4%) received diclofenac. Cox regression analysis adjusting for NSAIDs resulted in decreased recurrence risk (adjusted hazard ratio [HR{sub adjusted}] 0.84, 95% confidence interval [CI] 0.72–0.99; p = 0.042). Competing risk analysis confirmed the finding, with an HR{sub adjusted} of 0.76 (95% CI 0.60–0.97; p = 0.026). There was no significant effect on mortality or DFS. Sensitivity analysis of the effect of ibuprofen reported an HR{sub adjusted} of 0.83 (95% CI 0.70–1.00; p = 0.047). In restricted analyses of localized disease only (Union for International Cancer Control [UICC] I–II) and elective surgery only, no effect was found (localized: HR{sub adjusted} 0.81, 95% CI 0.62–1.06, p = 0.12; elective: HR{sub adjusted} 0.85, 95% CI 0.72–1.01, p = 0.063). Conclusions: Perioperative use of NSAIDs was associated with a reduced risk of cancer recurrence after resection for colorectal cancer. No effect on 5-year mortality or DFS was found.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Preoperative Radiomic Approach to Evaluate Tumor-Infiltrating CD8{sup +} T Cells in Hepatocellular Carcinoma Patients Using Contrast-Enhanced Computed Tomography

Background: To help identify potential hepatocellular carcinoma (HCC) candidates for immunotherapies, we aimed to develop and validate a radiomics-based biomarker (Rad score) to predict the infiltration of tumor-infiltrating CD8{sup +} T cells in HCC patients, and to evaluate the correlation of Rad score with tumor immune characteristics. Methods: Overall, 142 HCC patients (n = 100 and n = 42 in the training and validation sets, respectively) were subjected to radiomic feature extraction. Imaging features and immunochemistry data of patients in the training set were subjected to elastic-net regularized regression analysis to predict the level of CD8{sup +} T cell infiltration. Results: A Rad score for CD8{sup +} T-cell infiltration, which contained seven variables, was developed and was validated in the validation set (area under the curve [AUC]: training set 0.751, 95% confidence interval [CI] 0.656–0.846; validation set 0.705, 95% CI 0.547–0.863). The decision curve indicated the clinical usefulness of the Rad score. A higher Rad score correlated with superior overall and disease-free survival outcomes (p = 0.012 and 0.0088, respectively). Using the pathological slides, we found that the Rad score positively correlated with the percentage of tumor-infiltrating lymphocytes (TILs; Spearman rho = 0.51, p < 0.0001). Moreover, the Rad score could also discriminate inflamed tumors from immune-desert and immune-excluded tumors (Kruskal–Wallis, p < 0.0001), and higher Rad scores could be found in patients with positive programmed cell death ligand 1 expression in tumor/immune cells, as well as those with positive programmed cell death protein 1 expression. Conclusion: The newly developed Rad score was a powerful predictor of CD8{sup +} T-cell infiltration, which could be useful in identifying potential HCC patients who can benefit from immunotherapies when validated in large-scale prospective cohorts.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Modeling dynamics of acute HIV infection incorporating density-dependent cell death and multiplicity of infection

Understanding the dynamics of acute HIV infection can offer valuable insights into the early stages of viral behavior, potentially helping uncover various aspects of HIV pathogenesis. The standard viral dynamics model explains HIV viral dynamics during acute infection reasonably well. However, the model makes simplifying assumptions, neglecting some aspects of HIV infection. For instance, in the standard model, target cells are infected by a single HIV virion. Yet, cellular multiplicity of infection (MOI) may have considerable effects in pathogenesis and viral evolution. Further, when using the standard model, we take constant infected cell death rates, simplifying the dynamic immune responses. Here, we use four models—1) the standard viral dynamics model, 2) an alternate model incorporating cellular MOI, 3) a model assuming density-dependent death rate of infected cells and 4) a model combining (2) and (3)—to investigate acute infection dynamics in 43 people living with HIV very early after HIV exposure. We find that all models qualitatively describe the data, but none of the tested models is by itself the best to capture different kinds of heterogeneity. Instead, different models describe differing features of the dynamics more accurately. For example, while the standard viral dynamics model may be the most parsimonious across study participants by the corrected Akaike Information Criterion (AICc), we find that viral peaks are better explained by a model allowing for cellular MOI, using a linear regression analysis as analyzed by R 2 . These results suggest that heterogeneity in within-host viral dynamics cannot be captured by a single model. Depending on the specific aspect of interest, a corresponding model should be employed.

60 APPLIED LIFE SCIENCES↗

Relative Roles of Deterministic and Stochastic Processes in Driving the Vertical Distribution of Bacterial Communities in a Permafrost Core from the Qinghai-Tibet Plateau, China

Understanding the processes that influence the structure of biotic communities is one of the major ecological topics, and both stochastic and deterministic processes are expected to be at work simultaneously in most communities. Here, we investigated the vertical distribution patterns of bacterial communities in a 10-m-long soil core taken within permafrost of the Qinghai-Tibet Plateau. To get a better understanding of the forces that govern these patterns, we examined the diversity and structure of bacterial communities, and the change in community composition along the vertical distance (spatial turnover) from both taxonomic and phylogenetic perspectives. Measures of taxonomic and phylogenetic beta diversity revealed that bacterial community composition changed continuously along the soil core, and showed a vertical distance-decay relationship. Multiple stepwise regression analysis suggested that bacterial alpha diversity and phylogenetic structure were strongly correlated with soil conductivity and pH but weakly correlated with depth. There was evidence that deterministic and stochastic processes collectively drived bacterial vertically-structured pattern. Bacterial communities in five soil horizons (two originated from the active layer and three from permafrost) of the permafrost core were phylogenetically random, indicator of stochastic processes. However, we found a stronger effect of deterministic processes related to soil pH, conductivity, and organic carbon content that were structuring the bacterial communities. We therefore conclude that the vertical distribution of bacterial communities was governed primarily by deterministic ecological selection, although stochastic processes were also at work. Furthermore, the strong impact of environmental conditions (for example, soil physicochemical parameters and seasonal freeze-thaw cycles) on these communities underlines the sensitivity of permafrost microorganisms to climate change and potentially subsequent permafrost thaw.

Science & Technology - Other Topics↗

Using the concordance of in vitro and in vivo data to evaluate extrapolation assumptions

Linking in vitro bioactivity and in vivo toxicity on a dose basis enables the use of highthroughput in vitro assays as an alternative to traditional animal studies. In this study, we evaluated assumptions in the use of a high-throughput, physiologically based toxicokinetic (PBTK) model to relate in vitro bioactivity and rat in vivo toxicity data. The fraction unbound in plasma (fup) and intrinsic hepatic clearance (Clint) were measured for rats (for 67 and 77 chemicals, respectively), combined with fup and Clint literature data for 97 chemicals, and incorporated in the PBTK model. Of these chemicals, 84 had corresponding in vitro ToxCast bioactivity data and in vivo toxicity data. For each possible comparison of in vitro and in vivo endpoint, the concordance between the in vivo and in vitro data was evaluated by a regression analysis. For a base set of assumptions, the PBTK results were more frequently better associated than either the results from a “random” model parameterization or direct comparison of the “untransformed” values of AC50 and dose (performed best in 51%, 28%, and 21% of cases, respectively). We also investigated several assumptions in the application of PBTK for IVIVE, including clearance and internal dose selection. One of the better assumptions sets–restrictive clearance and comparing free in vivo venous plasma concentration with free in vitro concentration–outperformed the random and untransformed results in 71% of the in vitro-in vivo endpoint comparisons. These results demonstrate that applying PBTK improves our ability to observe the association between in vitro bioactivity and in vivo toxicity data in general. This suggests that potency values from in vitro screening should be transformed using in vitro-in vivo extrapolation (IVIVE) to build potentially better machine learning and other statistical models for predicting in vivo toxicity in humans

59 BASIC BIOLOGICAL SCIENCES↗