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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.

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At least 235 records · Page 13
All sourcesNASA NTRSDOE OSTI
DOE OSTI2012

High-Dose Conformal Radiotherapy Reduces Prostate Cancer-Specific Mortality: Results of a Meta-analysis

Purpose: To determine in a meta-analysis whether prostate cancer-specific mortality (PCSM), biochemical or clinical failure (BCF), and overall mortality (OM) in men with localized prostate cancer treated with conformal high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT). Methods and Materials: The MEDLINE, Embase, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing conformal HDRT with CDRT for localized prostate cancer. Results: Five randomized, controlled trials (2508 patients) that met the study criteria were identified. Pooled results from these randomized, controlled trials showed a significant reduction in the incidence of PCSM and BCF rates at 5 years in patients treated with HDRT (p = 0.04 and p < 0.0001, respectively), with an absolute risk reduction (ARR) of PCSM and BCF at 5 years of 1.7% and 12.6%, respectively. Two trials evaluated PCSM with 10 years of follow up. The pooled results from these trials showed a statistical benefit for HDRT in terms of PCSM (p = 0.03). In the subgroup analysis, trials that used androgen deprivation therapy (ADT) showed an ARR for BCF of 12.9% (number needed to treat = 7.7, p < 0.00001), whereas trials without ADT had an ARR of 13.6% (number needed to treat = 7, p < 0.00001). There was no difference in the OM rate at 5 and 10 years (p = 0.99 and p = 0.11, respectively) between the groups receiving HDRT and CDRT. Conclusions: This meta-analysis is the first study to show that HDRT is superior to CDRT in preventing disease progression and prostate cancer-specific death in trials that used conformational technique to increase the total dose. Despite the limitations of our study in evaluating the role of ADT and HDRT, our data show no benefit for HDRT arms in terms of BCF in trials with or without ADT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Breast Cancer Laterality Does Not Influence Survival in a Large Modern Cohort: Implications for Radiation-Related Cardiac Mortality

Objectives: Radiation therapy for left-sided breast cancer has been associated with an elevated risk of cardiac mortality, based on studies predating treatment planning based on computed tomography. This study assessed the impact of tumor laterality on overall survival (OS) in a large cohort treated with modern techniques, to indirectly determine whether left-sided treatment remains associated with increased cardiac mortality. Methods and Materials: Patients treated for breast cancer with breast conserving surgery and adjuvant external beam radiation therapy were identified in the National Cancer Database, and OS was compared based on tumor laterality using Kaplan-Meier analysis. Separate analyses were performed for noninvasive and invasive carcinoma and for breast-only and breast plus regional nodal radiation therapy. Multivariate regression analysis of OS was performed with demographic, pathologic, and treatment variables as covariates to adjust for factors associated with breast cancer–specific survival. Results: We identified 344,831 patients whose cancer was diagnosed from 1998 to 2006 with a median follow-up time of 6.04 years (range, 0-14.17 years). Clinical, tumor, and treatment characteristics were similar between laterality groups. Regional nodal radiation was used in 14.2% of invasive cancers. No OS difference was noted based on tumor laterality for patients treated with breast-only (hazard ratio [HR] 0.984, P=.132) and breast plus regional nodal radiation therapy (HR 1.001, P=.957). In multivariate analysis including potential confounders, OS was identical between left and right sided cancers (HR 1.002, P=.874). No significant OS difference by laterality was observed when analyses were restricted to patients with at least 10 years of follow-up (n=27,725), both in patients treated with breast-only (HR 0.955, P=.368) and breast plus regional nodal radiation therapy (HR 0.859, P=.155). Conclusions: Radiation therapy for left-sided breast cancer does not appear to increase the risk of death in this national database relative to right-sided tumors. Consequently, radiation therapy–induced cardiac disease may be less prominent than previously demonstrated.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Factors Associated With Early Mortality in Patients Treated With Concurrent Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

Purpose: Concurrent chemoradiation therapy (con-CRT) is recommended for fit patients with locally advanced non-small cell lung cancer (LA-NSCLC) but is associated with toxicity, and observed survival continues to be limited. Identifying factors associated with early mortality could improve patient selection and identify strategies to improve prognosis. Methods and Materials: Analysis of a multi-institutional LA-NSCLC database consisting of 1245 patients treated with con-CRT in 13 institutions was performed to identify factors predictive of 180-day survival. Recursive partitioning analysis (RPA) was performed to identify prognostic groups for 180-day survival. Multivariate logistic regression analysis was used to create a clinical nomogram predicting 180-day survival based on important predictors from RPA. Results: Median follow-up was 43.5 months (95% confidence interval [CI]: 40.3-48.8) and 127 patients (10%) died within 180 days of treatment. Median, 180-day, and 1- to 5-year (by yearly increments) actuarial survival rates were 20.9 months, 90%, 71%, 45%, 32%, 27%, and 22% respectively. Multivariate analysis adjusted by region identified gross tumor volume (GTV) (odds ratio [OR] ≥100 cm{sup 3}: 2.61; 95% CI: 1.10-6.20; P=.029) and pulmonary function (forced expiratory volume in 1 second [FEV{sub 1}], defined as the ratio of FEV{sub 1} to forced vital capacity [FVC]) (OR <80%: 2.53; 95% CI: 1.09-5.88; P=.030) as significant predictors of 180-day survival. RPA resulted in a 2-class risk stratification system: low-risk (GTV <100 cm{sup 3} or GTV ≥100 cm{sup 3} and FEV{sub 1} ≥80%) and high-risk (GTV ≥100 cm{sup 3} and FEV{sub 1} <80%). The 180-day survival rates were 93% for low risk and 79% for high risk, with an OR of 4.43 (95% CI: 2.07-9.51; P<.001), adjusted by region. A clinical nomogram predictive of 180-day survival, incorporating FEV{sub 1}, GTV, N stage, and maximum esophagus dose yielded favorable calibration (R{sup 2} = 0.947). Conclusions: This analysis identified several risk factors associated with early mortality and suggests that future research in the optimization of pretreatment pulmonary function and/or functional lung avoidance treatment may alter the therapeutic ratio in this patient population.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

The Henri Mondor Procedure of Morbidity and Mortality Review Meetings: Prospective Registration of Clinical, Dosimetric, and Individual Radiosensitivity Data of Patients With Severe Radiation Toxicity

Purpose: After radiation therapy (RT), various radiation-induced toxicities can develop in about one-fourth of patients. An international interest in using morbidity and mortality rates to monitor the quality of care and integrate morbidity and mortality review (MMR) meetings into organizations' governance processes has arisen. We report the first results of patients included in our MMR procedure that included biological assays for individual intrinsic radiosensitivity (IIRS). Methods and Materials: Twenty-three patients were prospectively included in the MMR database. Twenty-two were evaluable for IIRS. Prostate (n=10) and breast (n=8) cancers were the most frequent disease types. The total dose delivered, determined according to the type of disease, ranged from 30 to 74 Gy. Our MMR procedure requires strict criteria: patients with unresolved toxicity of grade 3 or higher with availability of clinical (photographic) data, IIRS results obtained from skin biopsy assays, treatment modalities, and follow-up data. The RT technique and dosimetry were reviewed. Results: Our prospective registration of toxicities showed mainly rectitis, occurring in 7 cases, and skin toxicities, occurring in 9. Of the 7 patients with rectitis, 5 received 66 Gy of post-prostatectomy RT with V50 (rectum volume receiving 50 Gy) ranging from 45% to 75% and a mean maximal dose of 66.5 Gy. For dermatitis and cystitis, the mean maximal doses were in the range of classical constraints without any overdosage or dose heterogeneity. No errors were found in the review of treatment planning and positioning. Conversely, all the patients were considered biologically as radiosensitive with genomic instability and ATM (ataxia telangiectasia mutated)-dependent DNA double-strand break repair impairments. Conclusions: The MMR review of files allowed clear answers for patients on the relationship between clinical events and their IIRS. Our procedure has allowed education of all our staff to monitor, identify, and document clinical, physical, and biological aspects of radiation-induced toxicities. Thus we recommend the introduction of the MMR procedure in RT departments.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Mortality, Transmitter Retention, Growth, and Wound Healing in Juvenile Salmon Injected with Micro Acoustic Transmitters

A cylindrical acoustic transmitter (AT; 0.2 g) has been developed for injection into the peritoneum of fish. Laboratory studies can provide tagging guidelines to minimize the effect of implantation techniques and transmitter burden (relative weight of the transmitter to the weight of the fish) in fish before a transmitter is used in field studies. The goal of this study was to examine response variables (mortality, transmitter expulsion, growth, wound area) of juvenile Chinook Salmon (Oncorhynchus tschawytscha; 65–104 mm fork length [FL]) injected with an AT along a wide range of sizes that could lead to a guideline for minimizing tagging effects. The overarching goal was to determine a minimum size threshold for fish that can be injected, while minimizing adverse transmitter effects. Juveniles (n = 700) were separated into four treatments: (1) acoustic transmitter injection (AT), (2) AT and a passive integrated transponder tag injection (AT+PIT), (3) visual implant elastomer injection (Marked control), and (4) unmarked (Unmarked control). Fish were evaluated weekly for four weeks, and again at the end of the study (60 d post-tagging). Fish injected with an AT or an AT+PIT experienced greater mortality than Marked controls. By 60 d post-tagging, transmitter expulsion was 44% for AT fish and 20% for AT+PIT fish. Fish injected with an AT or an AT+PIT grew (FL and weight gain) significantly less than Marked controls, and no minimum size thresholds were detected. Finally, initial size (FL) significantly affected wound area in AT and AT+PIT fish. A size threshold was only identified on Day 7 (85.1 mm) for AT+PIT fish, indicating that wound areas in fish < 85.1 mm were larger than wound areas of fish > 85.1 mm. This research suggests that injecting juveniles with an AT or an AT+PIT had a greater effect on smaller fish than larger fish.

Chinook↗
DOE OSTI2018

Associations between environmental quality and infant mortality in the United States, 2000–2005

Background: The United States (U.S.) suffers from high infant mortality (IM) rates and there are significant racial/ethnic differences in these rates. Prior studies on the environment and infant mortality are generally limited to singular exposures. We utilize the Environmental Quality Index (EQI), a measure of cumulative environmental exposure (across air, water, land, sociodemographic, and land domains) for U.S. counties from 2000 to 2005, to investigate associations between ambient environment and IM across maternal race/ethnicity. Methods: We linked 2000–2005 infant data from the U.S. Centers for Disease Control and Prevention to the EQI (n = 22,702,529; 144,741 deaths). We utilized multi-level regression to estimate associations between quartiles of county-level EQI and IM. We also considered associations between quartiles of county level domain specific indices with IM. We controlled for rural-urban status (RUCC1: urban, metropolitan; RUCC2: urban, non-metropolitan; RUCC3: less urbanized; RUCC4: thinly populated), maternal age, maternal education, marital status, infant sex, and stratified on race/ethnicity. Additionally, we estimated associations for linear combinations of environmental quality and rural-urban status. Results: We found a mix of positive, negative, and null associations and our findings varied across domain and race/ethnicity. Poorer overall environmental quality was associated with decreased odds among Non-Hispanic whites (OR and 95% CI: EQIQ4 (ref. EQIQ1): 0.84[0.80,0.89]). For Non-Hispanic blacks and Hispanics, some increased odds were observed. Poorer air quality was monotonically associated with increased odds among Non-Hispanic whites (airQ4 (ref. airQ1): 1.05[0.99,1.11]) and blacks (airQ4 (ref. airQ1): 1.09 [0.9,1.31]). Rural status was associated with increased IM odds among Hispanics (RUCC4-Q4:1.36[1.04,1.78]; RUCC1-Q4: 1.04[0.92,1.16], ref. for both RUCC1-Q1). Conclusions: This study is the first to report on associations between ambient environmental quality and IM across the United States. It corroborates prior research suggesting an association between air pollution and IM and identifies residence in thinly populated (rural) areas as a potential risk factor towards IM amongst Hispanics. Some of the counterintuitive findings highlight the need for additional research into potentially differential drivers of environmental quality across the rural-urban continuum, especially with regards to the sociodemographic environment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Updated Mortality Analysis of Radiation Workers at Rocketdyne (Atomics International), 1948-2008

Updated analyses of mortality data are presented on 46,970 workers employed 1948-1999 at Rocketdyne (Atomics International). Overall, 5,801 workers were involved in radiation activities, including 2,232 who were monitored for intakes of radionuclides, and 41,169 workers were engaged in rocket testing or other non-radiation activities. The worker population is unique in that lifetime occupational doses from all places of employment were sought, updated and incorporated into the analyses. Further, radiation doses from intakes of 14 different radionuclides were calculated for 16 organs or tissues using biokinetic models of the International Commission on Radiation Protection (ICRP). Because only negligible exposures were received by the 247 workers monitored for radiation activities after 1999, the mean dose from external radiation remained essentially the same at 13.5 mSv (maximum 1 Sv) as reported previously, as did the mean lung dose from external and internal radiation combined at 19.0 mSv (maximum 3.6 Sv). An additional 9 years of follow-up, from December 31,1999 through 2008, increased the person-years of observation for the radiation workers by 21.7% to 196,674 (mean 33.9 years) and the number of cancer deaths by 50% to 684. Analyses included external comparisons with the general population and the computation of standardized mortality ratios (SMRs) and internal comparisons using proportional hazards models and the computation of relative risks (RRs). A low SMR for all causes of death (SMR 0.82; 95% CI 0.78-0.85) continued to indicate that the Rocketdyne radiation workers were healthier than the general population and were less likely to die. The SMRs for all cancers taken together (SMR 0.88; 95% CI 0.81-0.95), lung cancer (SMR 0.87; 95% CI 0.76-1.00) and leukemia other than chronic lymphocytic leukemia (CLL) (SMR 1.04; 95% 0.67-1.53) were not significantly elevated. Cox regression analyses revealed no significant dose-response trends for any cancer. For all cancers excluding leukemia, the RR at 100 mSv was estimated as 0.98 (95% CI 0.82-1.17), and for all leukemia other than CLL it was 1.06 (95% CI 0.50-2.23). Uranium was the primary radionuclide contributing to internal exposures, but no significant increases in lung and kidney disease were seen. The extended follow-up reinforces the findings in the previous study in failing to observe a detectable increase in cancer deaths associated with radiation, but strong conclusions still cannot be drawn because of small numbers and relatively low career doses. Larger combined studies of early workers in the United States using similar methodologies are warranted to refine and clarify radiation risks after protracted exposures.

33 ADVANCED PROPULSION SYSTEMS↗
DOE OSTI2018

Determining the Impact of Forest Mortality in Semi-Arid Woodlands on Local and Regional Carbon Dynamics

We received funds in July 2012, and with supplemental funds, this funding ended in July 2017. Our overall project goals were to quantify the consequences of pinon mortality for carbon, water and energy exchange in pinon-juniper woodlands. To do this, we have been continuously measuring carbon, water and energy exchange using eddy covariance, over two pinon-juniper woodlands in central New Mexico. In one site, we girdled 1632 trees in the 4 ha surrounding the tower in Sept 2009. The other site, only 5 km away on the same plateau, was left intact, to serve as a control. We used this paired tower approach so we could directly evaluate the differences between how fluxes from disturbed and intact woodlands respond to the exact same climate conditions. In addition to eddy covariance measured fluxes from the two woodlands, we also made sap flux measurements, biomass, gas exchange, and soil respiration fluxes simultaneously in the two sites. The overall objective of this proposal is to measure the carbon and climate forcing consequences of widespread coniferous mortality events in the Southwestern US.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Avian Monitoring and Mortality Report at the National Wind Technology Center: January 2010 - February 2011

Tetra Tech EC, Inc. (Tetra Tech) conducted an avian monitoring and bird and bat mortality surveys at the National Wind Technology Center (NWTC) for NREL in 2010-2011. The purpose of the study was to quantify local avian use in the NWTC and vicinity and to estimate potential impacts to avian and bat species associated with the wind turbines and associated meteorological (met) towers at NWTC. Several different types of wind turbines are present on the NWTC with different capacities for energy production (1 kilowatt-3 megawatts [MW]; varying hub heights and turbine blade lengths) and met towers (guyed and unguyed) that vary in height (9.1-135 meters [m]). In a U.S. Department of Energy (DOE) review of three large turbine installations, DOE requested monitoring of avian and bat mortality be conducted, so that mitigation measures could be developed if needed.

17 WIND ENERGY↗
DOE OSTI2019

Evaluation of an acoustic deterrent to reduce bat mortalities at an Illinois wind farm

ABSTRACT From 2014 to 2016, GE Renewable Energy and California Ridge Wind Energy tested an ultrasonic bat deterrent system during the autumn bat migration period at an operating wind farm in Illinois, USA. The deterrent system consisted of air‐jet ultrasonic emitters mounted on nacelles and towers in a different configuration each year. Each year we conducted a randomized block experiment to determine whether the acoustic deterrent reduced bat mortalities at the wind farm. Effectiveness was based on estimates of bat mortalities during 3‐day trials. The operation of the acoustic deterrent resulted in significant overall bat fatality reductions of 29.2% ( = 7.5%) and 32.5% ( = 6.8%) in 2014 and 2015, respectively. All‐bat fatality rates were not reduced in 2016; however, annual all‐bat effectiveness estimates were influenced by species composition. We analyzed deterrent effectiveness for eastern red ( Lasiurus borealis ), hoary ( Lasiurus cinereus ), and silver‐haired ( Lasionycteris noctivagans ) bats, the 3 species most commonly found during the carcass searches. Hoary bats were consistently deterred each year, but annual deterrent effectiveness varied for eastern red and silver‐haired bats. © 2019 The Authors. Wildlife Society Bulletin published by Wiley Periodicals, Inc. on behalf of The Wildlife Society.

Romano, W. Brad↗
DOE OSTI2018

Xylem embolism refilling and resilience against drought-induced mortality in woody plants: processes and trade-offs

Understanding which species are able to recover from drought, under what conditions, and the mechanistic processes involved, will facilitate predictions of plant mortality in response to global change. In response to drought, some species die because of embolism-induced hydraulic failure, whilst others are able to avoid mortality and recover, following rehydration. Several tree species have evolved strategies to avoid embolism, whereas others tolerate high embolism rates but can recover their hydraulic functioning upon drought relief. Here, we focus on structures and processes that might allow some plants to recover from drought stress via embolism reversal. We provide insights into how embolism repair may have evolved, anatomical and physiological features that facilitate this process, and describe possible trade-offs and related costs. Recent controversies on methods used for estimating embolism formation/repair are also discussed, providing some methodological suggestions. Although controversial, embolism repair processes are apparently based on the activity of phloem and ray/axial parenchyma. The mechanism is energetically demanding, and the costs to plants include metabolism and transport of soluble sugars, water and inorganic ions. We propose that embolism repair should be considered as a possible component of a ‘hydraulic efficiency-safety’ spectrum. We also advance a framework for vegetation models, describing how vulnerability curves may change in hydrodynamic model formulations for plants that recover from embolism.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2019

A need to reduce premature CV mortality in the developing world: How could appropriate use of non-invasive imaging help?

We discuss premature deaths due to coronary heart disease (CHD) in developing countries and the importance of a comprehensive approach, involving clinical judgement, prevention, appropriate use of technology to diagnose and guide CHD treatment. Healthcare policies and levels of knowledge vary tremendously resulting heterogeneous utilization of diagnostic strategies and treatments worldwide. Many countries with high mortality have low utilization of non-invasive cardiac imaging. Appropriate use coupled with guideline-based management could help to improve care in the developing world and potentially result in better life expectancy already experienced by most high-income countries. In a scenario of increasing costs, a rational utilization of resources is imperative for all nations. A stepwise approach to suspected CHD is necessary, starting from good judgement, adding tests only as needed, preferably filtering patients who might benefit from advanced imaging. In stable patients, non-invasive tests should be used as filters to invasive procedure, preventing stable patients from undergoing revascularizations of questionable benefit. In this article, we review the relative role of exercise testing, myocardial perfusion imaging, and coronary computed tomography angiography to evaluate CHD and how these can be utilized as ways to help guide management that could impact premature mortality in developing nations.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Long-term Cardiac Mortality After Hypofractionated Radiation Therapy in Breast Cancer

Purpose: To explore very-long-term mortality from ischemic heart disease (IHD) after locoregional radiation therapy of breast cancer (BC) in relation to degree of hypofractionation and other treatment variables. Methods and Materials: Two hypofractionated regimens used for locoregional radiation therapy for BC from 1975 to 1991 were considered. Patients received 4.3 Gy × 2/week (10 fractions; target dose 43 Gy; n=1107) or 2.5 Gy × 5/week (20 fractions; target dose 50 Gy; n=459). To estimate cardiac doses, radiation fields were reconstructed in a planning system. Time to death from IHD was the endpoint, comparing the groups with each other and with age-matched, cancer-free control individuals, modeled with the Cox proportional hazards model. Results: Patients given 4.3 Gy × 10 had an increased risk of dying of IHD compared with both the 2.5 Gy group (hazard ratio [HR] = 2.37; 95% confidence interval [CI]: 1.06-5.32; P=.036) and the control group (HR = 1.59; 95% CI: 1.13-2.23; P=.008). Photon beams for parasternal fields gave an increased risk of dying of IHD compared with electron beams (HR = 2.56; 95% CI: 1.12-5.84; P=.025). Multivariate analysis gave an increased risk for the 4.3-Gy versus 2.5-Gy regimen with borderline significance (HR = 2.90; 95% CI: 0.97-8.79; P=.057) but not for parasternal irradiation. Conclusions: The degree of hypofractionation and parasternal photon beams contributed to increased cardiac mortality in this patient cohort. Differences emerged after 12 to 15 years, indicating the need of more studies with observation time of 2 decades.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2025

Rapid climate action is needed: comparing heat vs. COVID-19-related mortality

Abstract The impacts of climate change on human health are often underestimated or perceived to be in a distant future. Here, we present the projected impacts of climate change in the context of COVID-19, a recent human health catastrophe. We compared projected heat mortality with COVID-19 deaths in 38 cities worldwide and found that in half of these cities, heat-related deaths could exceed annual COVID-19 deaths in less than ten years (at + 3.0 °C increase in global warming relative to preindustrial). In seven of these cities, heat mortality could exceed COVID-19 deaths in less than five years. Our results underscore the crucial need for climate action and for the integration of climate change into public health discourse and policy.

Science & Technology - Other Topics↗
DOE OSTI2018

Injury and mortality of two Mekong River species exposed to turbulent shear forces

Global hydropower development is one solution proposed to address the increase in energy needs. However, hydropower-related impacts on riverine ecological systems are not well understood. The Mekong River Basin (MRB) is one of the world’s largest waterways and is presently experiencing significant hydropower expansion. It is also one of the most biodiverse rivers; serving as home to many species that are blocked or hindered by the development of dams. One source of injury and mortality for downstream moving fishes is passage through the turbine environment where fishes may be exposed to several physical stressors (e.g. shear forces, rapid decompression, blade strike and turbulence). The current study sought to understand the susceptibility of blue gourami ( Trichopodus trichopterus ) and iridescent shark ( Pangasianodon hypophthalmus ) to shear forces. Fishes were exposed to an underwater jet with velocities up to 21.3 m s –1 (equating to strain rates of up to 1185 s –1 ) and were assessed for behavioural effects, injuries and mortality. Overall, it was determined that both species were susceptible to the shear forces applied in this study and the effects were more pronounced at higher strain rates. Gouramis were more susceptible than sharks. Furthermore to minimise impacts on these species, shear forces within turbines should not exceed critical limits.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

A lincRNA connected to cell mortality and epigenetically-silenced in most common human cancers

Immortality is an essential characteristic of human carcinoma cells. We recently developed an efficient, reproducible method that immortalizes human mammary epithelial cells (HMEC) in the absence of gross genomic changes by targeting 2 critical senescence barriers. Consistent transcriptomic changes associated with immortality were identified using microarray analysis of isogenic normal finite pre-stasis, abnormal finite post-stasis, and immortal HMECs from 4 individuals. A total of 277 genes consistently changed in cells that transitioned from post-stasis to immortal. Gene ontology analysis of affected genes revealed biological processes significantly altered in the immortalization process. These immortalization-associated changes showed striking similarity to the gene expression changes seen in The Cancer Genome Atlas (TCGA) clinical breast cancer data. The most dramatic change in gene expression seen during the immortalization step was the downregulation of an unnamed, incompletely annotated transcript that we called MORT, for mortality, since its expression was closely associated with the mortal, finite lifespan phenotype. We show here that MORT (ZNF667-AS1) is expressed in all normal finite lifespan human cells examined to date and is lost in immortalized HMEC. MORT gene silencing at the mortal/immortal boundary was due to DNA hypermethylation of its CpG island promoter. This epigenetic silencing is also seen in human breast cancer cell lines and in a majority of human breast tumor tissues. The functional importance of DNA hypermethylation in MORT gene silencing is supported by the ability of 5-aza-2'- deoxycytidine to reactivate MORT expression. Analysis of TCGA data revealed deregulation of MORT expression due to DNA hypermethylation in 15 out of the 17 most common human cancers. In conclusion, the epigenetic silencing of MORT in a large majority of the common human cancers suggests a potential fundamental role in cellular immortalization during human carcinogenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Mitigating drought mortality by incorporating topography into variable forest thinning strategies

Abstract Drought-induced productivity reductions and tree mortality have been increasing in recent decades in forests around the globe. Developing adaptation strategies hinges on an adequate understanding of the mechanisms governing the drought vulnerability of forest stands. Prescribed reduction in stand density has been used as a management tool to reduce water stress and wildfire risk, but the processes that modulate fine-scale variations in plant water supply and water demand are largely missing in ecosystem models. We used an ecohydrological model that couples plant hydraulics with groundwater hydrology to examine how within-stand variations in tree spatial arrangements and topography might mitigate forest vulnerability to drought at individual-tree and stand scales. Our results demonstrated thinning generally ameliorated plant hydraulic stress and improved carbon and water fluxes of the remaining trees, although the effectiveness varied by climate and topography. Variable thinning that adjusted thinning intensity based on topography-mediated water availability achieved higher stand productivity and lower mortality risk, compared to evenly-spaced thinning at comparable intensities. The results from numerical experiments provided mechanistic evidence that topography mediates the effectiveness of thinning and highlighted the need for an explicit consideration of within-stand heterogeneity in trees and abiotic environments when designing forest thinning to mitigate drought impacts.

Environmental Sciences & Ecology↗