Ambient Oxygen Conditions Research Articles

Spatial and seasonal variability in benthic impact of mussel farms: Predicting and mitigating impacts using ambient oxygen conditions

Environmental impacts are a cause for concern when developing and expanding aquaculture and to be sustainable potential negative effects need to be addressed. The intensity and extent of these impacts likely vary among sites and seasons, depending on multiple factors including the physical and biological setting and operational aspects. Using a combination of sampling techniques, we investigated the spatial variability in epibenthic impacts in eleven commercial mussel farms, on the Swedish west coast. We found increased levels of organic content, changes in epibenthic macrofauna and increased cover of Beggiatoa sp., a documented indicator of hypoxia. The extent of these impacts was generally limited to the extent of the farms. Because the cover of Beggiatoa sp. was particularly clear and because oxygen conditions in the sediment is of great importance to the structure and function of these habitats, we analysed spatial patterns using an index of the benthic footprint (BFI) accounting for both intensity and extent of impacts. In the summer, the BFI varied strongly among farm-sites and subsequent analyses showed that it highly correlated with ambient bottom oxygen concentration. Repeated sampling during early spring, however, showed that impacts were quickly reversible also in the most impacted sites. Thus, we conclude that in Swedish coastal waters the benthic footprint calculated on the % cover of Beggiatoa sp. is highly dependent on ambient oxygen concentration. We suggest that knowledge about spatial and temporal patterns of oxygen in the bottom water can be used to predict the severity of impacts and provide an important criterion in a site-selection process aimed at developing a sustainable food industry.

Visualizing hydrogen peroxide and nitric oxide dynamics in endothelial cells using multispectral imaging under controlled oxygen conditions

The complex interplay between hydrogen peroxide (H2O2) and nitric oxide (NO) in endothelial cells presents challenges due to technical limitations in simultaneous measurement, hindering the elucidation of their direct relationship. Previous studies have yielded conflicting findings regarding the impact of H2O2 on NO production. To address this problem, we employed genetically encoded biosensors, HyPer7 for H2O2 and geNOps for NO, allowing simultaneous imaging in single endothelial cells. Optimization strategies were implemented to enhance biosensor performance, including camera binning, temperature regulation, and environmental adjustments to mimic physiological normoxia. Our results demonstrate that under ambient oxygen conditions, H2O2 exhibited no significant influence on NO production. Subsequent exploration under physiological normoxia (5 kPa O2) revealed distinct oxidative stress levels characterized by reduced basal HyPer7 signals, enhanced H2O2 scavenging kinetics, and altered responses to pharmacological treatment. Investigation of the relationship between H2O2 and NO under varying oxygen conditions revealed a lack of NO response to H2O2 under hyperoxia (18 kPa O2) but a modest NO response under physiological normoxia (5 kPa O2). Importantly, the NO response was attenuated by l-NAME, suggesting activation of eNOS by endogenous H2O2 generation upon auranofin treatment. Our study highlights the intricate interplay between H2O2 and NO within the endothelial EA.hy926 cell line, emphasizing the necessity for additional research within physiological contexts due to differential response observed under physiological normoxia (5 kPa O2). This further investigation is essential for a comprehensive understanding of the H2O2 and NO signaling considering the physiological effects of ambient O2 levels involved.

An atomically dispersed Co catalyst for efficient oxidative fabrication of benzoheterocycles under ambient oxygen conditions

The first Co1/NC SAC is reported to produce benzoheterocycles under oxygen conditions, and the yields of 2-PBO, 2-PBT and 2-PBM were 99%, 95% and 99%, respectively.

Cardioprotective Effects of Dexmedetomidine in an Oxidative-Stress In Vitro Model of Neonatal Rat Cardiomyocytes.

Preterm birth is a risk factor for cardiometabolic disease. The preterm heart before terminal differentiation is in a phase that is crucial for the number and structure of cardiomyocytes in further development, with adverse effects of hypoxic and hyperoxic events. Pharmacological intervention could attenuate the negative effects of oxygen. Dexmedetomidine (DEX) is an α2-adrenoceptor agonist and has been mentioned in connection with cardio-protective benefits. In this study, H9c2 myocytes and primary fetal rat cardiomyocytes (NRCM) were cultured for 24 h under hypoxic condition (5% O2), corresponding to fetal physioxia (pO2 32-45 mmHg), ambient oxygen (21% O2, pO2 ~150 mmHg), or hyperoxic conditions (80% O2, pO2 ~300 mmHg). Subsequently, the effects of DEX preconditioning (0.1 µM, 1 µM, 10 µM) were analyzed. Modulated oxygen tension reduced both proliferating cardiomyocytes and transcripts (CycD2). High-oxygen tension induced hypertrophy in H9c2 cells. Cell-death-associated transcripts for caspase-dependent apoptosis (Casp3/8) increased, whereas caspase-independent transcripts (AIF) increased in H9c2 cells and decreased in NRCMs. Autophagy-related mediators (Atg5/12) were induced in H9c2 under both oxygen conditions, whereas they were downregulated in NRCMs. DEX preconditioning protected H9c2 and NRCMs from oxidative stress through inhibition of transcription of the oxidative stress marker GCLC, and inhibited the transcription of both the redox-sensitive transcription factors Nrf2 under hyperoxia and Hif1α under hypoxia. In addition, DEX normalized the gene expression of Hippo-pathway mediators (YAP1, Tead1, Lats2, Cul7) that exhibited abnormalities due to differential oxygen tensions compared with normoxia, suggesting that DEX modulates the activation of the Hippo pathway. This, in the context of the protective impact of redox-sensitive factors, may provide a possible rationale for the cardio-protective effects of DEX in oxygen-modulated requirements on survival-promoting transcripts of immortalized and fetal cardiomyocytes.

Seasonal, environmental and individual effects on hypoxia tolerance of eastern sand darter (Ammocrypta pellucida).

Metabolic rate and hypoxia tolerance are highly variable among individual fish in a stable environment. Understanding the variability of these measures in wild fish populations is critical for assessing adaptive potential and determining local extinction risks as a result of climate-induced fluctuations in temperature and hypoxic conditions. We assessed the field metabolic rate (FMR) and two hypoxia tolerance metrics, oxygen pressure at loss of equilibrium (PO2 at LOE) and critical oxygen tolerance (Pcrit) of wild-captured eastern sand darter (Ammocrypta pellucida), a threatened species in Canada, using field trials (June to October) that encompassed ambient water temperatures and oxygen conditions typically experienced by the species. Temperature was significantly and positively related to hypoxia tolerance but not FMR. Temperature alone explained 1%, 31% and 7% of the variability observed in FMR, LOE, and Pcrit, respectively. Environmental and fish-specific factors such as reproductive season and condition explained much of the residual variation. Reproductive season significantly affected FMR by increasing it by 159-176% over the tested temperature range. Further understanding the impact of reproductive season on metabolic rate over a temperature range is crucial for understanding how climate change could impact species fitness. Among-individual variation in FMR significantly increased with temperature while among-individual variation in both hypoxia tolerance metrics did not. A large degree of variation in FMR in the summer might allow for evolutionary rescue with increasing mean and variance of global temperatures. Findings suggest that temperature may be a weak predictor in a field setting where biotic and abiotic factors can act concurrently on variables that affect physiological tolerance.

A parametric investigation of methane jets in direct-injection compression-ignition conditions

This work investigated the effects of ambient and injection conditions on the autoignition, flame evolution and combustion characteristics of the natural gas jets at direct-injection (DI) compression-ignition (CI) conditions. Methane (CH4, as a natural gas surrogate) was directly injected into an optically accessible constant-volume combustion chamber (CVCC). For the experiments, the ambient gas density within the CVCC was fixed at 24kgm−3, but other ambient conditions were varied, including ambient gas temperature (1060–1200K) and ambient oxygen concentration (10–21 vol.%). The effects of injection pressure (10–20MPa reservoir pressure) were also assessed at a fixed ambient temperature and ambient oxygen conditions of 1200K and 21 vol.%, respectively. High-speed schlieren imaging, heat release rate analysis and flame luminosity measurement were applied to the CH4 jet flames. The results show that the ignition delay decreases with increasing ambient temperature or ambient oxygen concentration but does not display an apparent trend with changing injection pressure. Optical images reveal that the CH4 jet combustion typically starts from a localised kernel before propagating downstream of the jet volume in most cases, other than the lower ambient oxygen concentration case. The optical results also reveal that after ignition, the CH4 jet flame recesses back towards the nozzle before stabilising at a lift-off distance. The jet becomes more lifted with a decreasing ambient temperature, a reducing ambient oxygen concentration, and an increasing reservoir pressure. The results also reveal that the heat release rate and flame luminosity profiles roughly correspond to the ignition and combustion characteristics of the CH4 jet flames.

Pulmonary Arterial Pressure Changes Under Dobutamine Stress Echocardiography in Non-Anemic Iron Deficient COPD Subjects.

PurposeNon-anemic iron deficiency (NAID) is common in COPD, and could induce functional/structural changes in the pulmonary vascular bed. Thus, we aimed to study, during resting and ambient oxygen conditions, the systolic pulmonary arterial pressure (sPAP) changes during dobutamine stress echocardiography (DSE) for NAID+ compared to NAID- subjects with COPD.Patients and MethodsWe analyzed 24 patients with COPD and evaluated their clinical parameters, including lung function and serum iron profile, followed by the changes in the sPAP under DSE.ResultsTen subjects with NAID+ were compared with fourteen NAID- subjects for sPAP measurement. At baseline, only left atrial volume was significantly different between groups (30±4 vs 23±5 mL*m2), respectively (p-value=0.002). For the right side, tricuspid annular plane systolic excursion (TAPSE) was similar between-groups (22±2 vs 20±4, p-value >0.05), at baseline. The sPAP (mmHg) changes were also not significantly different between groups (pre 32±14 vs peak 48±14 for NAID+ and pre 29±7 vs peak 43±10 for NAID-, Group p-value=0.400, Time p-value <0.0001, and Interaction p-value=0.606).ConclusionCOPD subjects with NAID do not show increased sPAP responses during DSE, compared with iron-replete subjects.

Endogenous glutamine is rate-limiting for anti-CD3 and anti-CD28 induced CD4+ T-cell proliferation and glycolytic activity under hypoxia and normoxia

To meet the demand for energy and biomass, T lymphocytes (T cells) activated to proliferation and clonal expansion, require uptake and metabolism of glucose (Gluc) and the amino acid (AA) glutamine (Gln). Whereas exogenous Gln is converted to glutamate (Glu) by glutaminase (GLS), Gln is also synthesized from the endogenous pool of AA through Glu and activity of glutamine synthase (GS). Most of this knowledge comes from studies on cell cultures under ambient oxygen conditions (normoxia, 21% O2). However, in vivo, antigen induced T-cell activation often occurs under moderately hypoxic (1–4% O2) conditions and at various levels of exogenous nutrients. Here, CD4+ T cells were stimulated for 72 h with antibodies targeting the CD3 and CD28 markers at normoxia and hypoxia (1% O2). This was done in the presence and absence of the GLS and GS inhibitors, Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (BPTES) and methionine sulfoximine (MSO) and at various combinations of exogenous Gluc, Gln and pyruvate (Pyr) for the last 12 h of stimulation. We found that T-cell proliferation, viability and levels of endogenous AA were significantly influenced by the availability of exogenous Gln, Gluc and Pyr as well as inhibition of GLS and GS. Moreover, inhibition of GLS and GS and levels of oxygen differentially influenced oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Finally, BPTES-dependent down-regulation of ECAR was associated with reduced hexokinase (HK) activity at both normoxia and hypoxia. Our results demonstrate that Gln availability and metabolism is rate-limiting for CD4+ T-cell activity.

A parametric study of autoigniting hydrogen jets under compression-ignition engine conditions

This study examines the flame evolution of autoigniting H2 jets with high-speed schlieren and OH∗ chemiluminescence optical methods in a constant-volume combustion chamber over a wide range of simulated compression-ignition engine conditions. Parametric variations include the injector nozzle orifice diameter (0.31–0.83 mm), injection reservoir pressure (100–200 bar), ambient temperature (1000–1140 K), density (12.5–24 kg/m3) and O2 concentration (10–21 vol.%). The jet ignition delay was found to be highly sensitive to changes in ambient temperature while all other parameter variations resulted in minor ignition delay changes. Optical imaging reveals that in most cases, the reaction front of the H2 jet initiates from a localised kernel, before engulfing the entire jet volume downstream and recessing towards the nozzle. The flames attach to the nozzle, except at the lowest ambient oxygen condition of 10 vol.% O2 for which a lifted flame is observed. The H2 diffusion flame length shows a dependence on both the mass flow rate and the level of O2 entrainment that follows the same correlations as previously established for atmospheric H2 jet flames.

Implementation of multi-component diesel fuel surrogates and chemical kinetic mechanisms for engine combustion simulations

Recent developments have led to the formulation of multi-component surrogates that closely match physical and chemical properties of diesel fuels. These surrogates have been characterized and extensively tested in constant pressure vessels as well as engine experiments. The adoption of such surrogates in simulations is an important step towards predictive engine simulations. However, significant challenges remain in adoption of such surrogates. The complex chemical kinetics associated with a multi-component fuel leads to an extremely large and stiff chemistry mechanism with thousands of species. Such chemistry mechanisms are prohibitive to be directly used in engine simulations using traditional solvers due to the excessively-high computational cost. This work describes some of the experimental investigations of a 4-component diesel fuel surrogate in constant volume combustion chambers that provide useful validation datasets for numerical models. In addition, a chemical kinetic mechanism for the multi-component diesel surrogate with 1544 species is proposed. A previously validated unsteady flamelet model, accelerated by a sparse solver and analytical Jacobian, is used to implement large chemistry mechanisms for realistic diesel engine simulations. A flamelet solver is used to generate multi-dimensional unsteady flamelet libraries for the multi-component surrogate for a range of conditions. This approach is then used in a large eddy simulation (LES) framework to model combustion of the 4-component surrogate in a constant pressure spray vessel over a range of ambient oxygen conditions. The current chemistry mechanism and computational methodology can capture the two-step ignition delay as well as flame lift-off length trends observed in the experiments. Some of the low temperature combustion characteristics are analyzed in detail. The computational setup and the validation results demonstrate the feasibility of using these latest multi-component fuel surrogates for engine simulations by leveraging multi-dimensional chemistry tabulation methods.Highlights:1. Detailed experiments with the multicomponent V0A surrogate were carried out in the High Temperature Pressure Vessel facility.2. A detailed chemistry mechanism with 1544 species was developed for the V0A surrogate.3. The LSODES based flamelet tabulation method was used to implement and validate these high-fidelity surrogates and mechanisms in engine relevant LES calculations.

Abstract 337: A metastatic phenotype is reproduced in spheroids containing patient-specific cancer cells and mesenchymal stem cells

Abstract Reproducible, scalable, and patient-specific 3D models of the tumor microenvironment are required to study tumor growth, metastasis and dormancy. In this study, patient-derived cancer cells, mesenchymal stem cells (MSCs), and optimization of the oxygen level and extracellular matrix (ECM) were incorporated in the development of a spheroid system using 5 cancer cell models (pancreatic [Panc], lung adenocarcinoma [LA], colon adenocarcinoma [CA], endometrioid ovarian [EO] and high-grade serous carcinoma [HGSC]). The cell models were isolated and scaled up using a feeder-free culture medium in either ambient oxygen (approximately 21% O2) or hypoxic (5% O2) conditions, depending on the individual model requirements. Cell migration was assessed via monolayer scratch assays, and the relative rates were compared to the T stage of the tumor from which the models were derived. To assess spheroid formation, the 5 models were cultured in ECM-containing medium. The Panc and HGSC spheroids were also generated with the addition of MSCs at ratios of 1-100 MSCs per 100 cancer cells. The relative rates of migration of the cell models in ambient oxygen (CA &amp;gt; EO ≈ Panc &amp;gt; HGSC ≈ LA) differed significantly from that in 5% O2 (CA = Panc = HGSC &amp;gt; EO &amp;gt; LA). Interestingly, the T stage of the original tumors (CA = Panc = HGSC &amp;gt; LA &amp;gt; EO) correlated more closely to the relative rate of cell migration when the cell models were cultured in 5% compared to 21% O2. When cultured in a 3D (spheroid) format containing ECM, the Panc and EO models demonstrated increased invasion into the surrounding ECM compared to the LA, HGSC, and CA models. The addition of MSCs into the LA model dramatically increased the invasive phenotype of the LA model. A seeding ratio of 1:100 MSC:LA cells enabled spheroid formation and invasion into the ECM, previously unobserved for the LA model in this format. The Panc model became extremely aggressive with respect to invasion into the ECM, at a ratio as low as 1:100 MSCs to cancer cells. In pilot studies with the Panc and HGSC models, spheroid size and invasion into the ECM increased upon adding the MSCs. Spheroid diameter increased by approximately 30%, and there was a notable increase in invasiveness of the already mobile and invasive Panc cancer cells into the surrounding ECM. We present here an efficient, patient-specific, spheroid model system representing dormant and metastatic tumor states that is suitable for studying antitumor drug response, personalized therapy, and disease mechanisms. The relative rates of cell migration positively correlated with the T stage of the original tumors in the more physiologically-relevant oxygen condition (5%), underscoring the need to optimize this parameter during model development. Continued optimization will include incorporating tissue-specific ECMs from lung, liver and pancreas, and assessing the robustness and scalability of these models for high-throughput drug screens. Citation Format: Dmitry Shvartsman, Amy Pepicelli, Liam Deems, David Deems, Elin S. Agoston, Amit Shahar. A metastatic phenotype is reproduced in spheroids containing patient-specific cancer cells and mesenchymal stem cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 337.

Three-Dimensional, Scaffolded Tumor Model to Study Cell-Driven Microenvironment Effects and Therapeutic Responses.

Development of novel therapeutics is limited by a lack of accurate preclinical models for testing, specifically the inability of traditional 2D culture (monolayer) to accurately mimic in vivo tumors. In this work, lyophilized silk fibroin scaffolds were used to develop 3D neuroblastoma models (scaffolded NB) using multiple neuroblastoma cell lines (SK-N-AS, KELLY, and SH-SY5Y). Cells grown on scaffolds in low (1%) and ambient (21%) oxygen were compared to traditional monolayer cell culture. Monolayer cultures under low oxygen conditions exhibited increased expression of hypoxia-related genes such as VEGF, CAIX, and GLUT1. Scaffolded NB exhibited increased hypoxia-related gene expression under both low and ambient oxygen conditions. Pimonidazole staining confirmed the presence of hypoxic regions in the scaffolded NB. Cytokine secretion in the monolayer and scaffolded NB suggested differential secretion of cytokines due to both oxygen concentration (ex. VEGF, CCL3, and uPAR) and scaffolded culture (ex. IL-8, GM-CSF, and ITAC). Response to etoposide, a standard chemotherapeutic, demonstrated a reduced cytotoxicity in scaffolded culture as compared to monolayer culture regardless of oxygen concentration. However, use of a hypoxia-activated therapeutic, tirapazamine, exhibited cytotoxicity under scaffolded, ambient oxygen conditions and under monolayer and scaffolded, low oxygen conditions. Overall, this culture system provides a platform to study neuroblastoma and to assess the impact of hypoxia on tumor-relevant pathways and environments to aid in development of novel targeted therapeutics.

The Importance and Clinical Implications of FLASH Ultra-High Dose-Rate Studies for Proton and Heavy Ion Radiotherapy.

The goal of radiation therapy is to provide the highest probability of tumor control while minimizing normal tissue toxicity. Recently, it has been discovered that ultra-high dose rates of ionizing radiation may preferentially spare normal tissue over tumor tissue. This effect, referred to as FLASH radiotherapy, has been observed in various animal models as well as, more recently, in a human patient. This effect may be related to the cell sparing found in vitro at ultra-high dose rates of photons and electrons dating back to the 1960s. Conditions representative of physiologic oxygen were found to be essential for this process to occur. However, there is no conclusive data on whether this effect occurs with protons, as all results to date have been in cells irradiated at ambient oxygen conditions. There have been no ultra-high dose-rate experiments with heavy ions, which would be relevant to the implementation of FLASH to carbon-ion therapy. These basic science results are critical in guiding this rapidly advancing field, since clinical particle therapy machines capable of FLASH dose rates have already been promoted for protons. To help ensure FLASH radiotherapy is reliable and maximally effective, the radiobiology must keep ahead of the clinical implementation to help guide it. In this context, in vitro and in vivo proton and heavy ion experiments involving FLASH dose rates need to be performed to evaluate not only short-term consequences, but also sequelae related to long-term health risks. Critical to these future studies is consideration of relevant oxygen tensions at the time of irradiation, as well as appropriate in silico modeling to assist in understanding the initial physicochemical events.

Effects of isopropanol-butanol-ethanol and diesel fuel blends on combustion characteristics in a constant volume chamber

Acetone-butanol-ethanol (ABE) has been directly used in modern engines as a way to eliminate the high separation cost during the butanol fermentation process. Nevertheless, further development of ABE could be restricted by the corrosiveness of acetone in the mixture. By converting ABE into Isopropanol-Butanol-Ethanol (IBE) in a single biochemical step, a different yet more stable alternative fuel could be available. This study is aimed to investigate the performance, combustion, and soot luminosity of a constant volume chamber fueled with varying ratios of IBE and diesel. IBE blended at 20% and 40% with 80% and 60% diesel, by volume respectively, and neat diesel were compared under various ambient oxygen and temperature conditions. Overall, the IBE-diesel blends were able to maintain combustion and spray characteristics similar to that of neat diesel while at the same time reducing soot. However, at lower temperatures and oxygen concentrations, the IBE-diesel blends show higher ignition delays which affect the combustion.

Assessment of surface water quality using water quality index and multivariate statistical analyses in Saraydüzü Dam Lake, Turkey.

In this study, observations were carried out in the surface waters of Saraydüzü Dam Lake within Sinop provincial borders for 1year to determine water quality. The basic 28 variables used to determine water quality were measured monthly at six stations. Taking into account the World Health Organization's drinking water standards, the water quality index (WQI) and Turkey's Ministry of Forestry and Water Affairs Surface Water Quality Regulations (SWQR) were used in determining the water quality. In addition, irrigation water quality was examined. For this, sodium absorption rates (SAR), sodium percentage and residual sodium carbonate (RSC) values were calculated. WQI values in the lake were found to be between 17.62 and 29.88. Water quality parameters did not exceed the recommended limit values in all months and at all stations. According to these values, the Saraydüzü Dam Lake water belongs to the 'very good' class in terms of drinking water quality. The results obtained showed that there were no nitrogen or phosphate inputs that could harm the ecosystem in the lake and that there were no low/insufficient ambient oxygen conditions resulting from excessive oxygen consumption during the degradation process of organic matter. All water quality parametres are well below the permissible limits except some heavy metals according to SWQR. Cu, Zn and Fe were found to exceed the limit values. The water quality of irrigation water was found to be good in terms of SAR and sodium percentage, whereas RSC was observed to have varying qualities during the year and not be suitable for irrigation in some months. According to results of factor analysis (FA), pH, temperature, electrical conductivity, suspended solid matter (SSM), biological oxygen demand (BOD), total hardness (TH),total alkalinity (TA), calcium, nitrate, ammonium, mercury and dissolved oxygen are the main variables responsible for the processes in the ecosystem.

Derivation of Breast Cancer Cell Lines Under Physiological (5%) Oxygen Concentrations.

Background: Most human breast cancer cell lines currently in use were developed and are cultured under ambient (21%) oxygen conditions. While this is convenient in practical terms, higher ambient oxygen could increase oxygen radical production, potentially modulating signaling pathways. We have derived and grown a series of four human breast cancer cell lines under 5% oxygen, and have compared their properties to those of established breast cancer lines growing under ambient oxygen.Methods: Cell lines were characterized in terms of appearance, cellular DNA content, mutation spectrum, hormone receptor status, pathway utilization and drug sensitivity.Results: Three of the four lines (NZBR1, NZBR2, and NZBR4) were triple negative (ER-, PR-, HER2-), with NZBR1 also over-expressing EGFR. NZBR3 was HER2+ and ER+ and also over-expressed EGFR. Cell lines grown in 5% oxygen showed increased expression of the hypoxia-inducible factor 1 (HIF-1) target gene carbonic anhydrase 9 (CA9) and decreased levels of ROS. As determined by protein phosphorylation, NZBR1 showed low AKT pathway utilization while NZBR2 and NZBR4 showed low p70S6K and rpS6 pathway utilization. The lines were characterized for sensitivity to 7-hydroxytamoxifen, doxorubicin, paclitaxel, the PI3K inhibitor BEZ235 and the HER inhibitors lapatinib, afatinib, dacomitinib, and ARRY-380. In some cases they were compared to established breast cancer lines. Of particular note was the high sensitivity of NZBR3 to HER inhibitors. The spectrum of mutations in the NZBR lines was generally similar to that found in commonly used breast cancer cell lines but TP53 mutations were absent and mutations in EVI2B, LRP1B, and PMS2, which have not been reported in other breast cancer lines, were detected. The results suggest that the properties of cell lines developed under low oxygen conditions (5% O2) are similar to those of commonly used breast cancer cell lines. Although reduced ROS production and increased HIF-1 activity under 5% oxygen can potentially influence experimental outcomes, no difference in sensitivity to estrogen or doxorubicin was observed between cell lines cultured in 5 vs. 21% oxygen.

The influence of oxygen and methane on nitrogen fixation in subarctic Sphagnum mosses

Biological nitrogen fixation is an important source of bioavailable nitrogen in Sphagnum dominated peatlands. Sphagnum mosses harbor a diverse microbiome including nitrogen-fixing and methane (CH4) oxidizing bacteria. The inhibitory effect of oxygen on microbial nitrogen fixation is documented for many bacteria. However, the role of nitrogen-fixing methanotrophs in nitrogen supply to Sphagnum peat mosses is not well explored. Here, we investigated the role of both oxygen and methane on nitrogen fixation in subarctic Sphagnum peat mosses. Five species of Sphagnum mosses were sampled from two mesotrophic and three oligotrophic sites within the Lakkasuo peatland in Orivesi, central Finland. Mosses were incubated under either ambient or low oxygen conditions in the presence or absence of methane. Stable isotope activity assays revealed considerable nitrogen-fixing and methane-assimilating rates at all sites (1.4 ± 0.2 µmol 15N–N2 g−1 DW day−1 and 12.0 ± 1.1 µmol 13C–CH4 g−1 DW day−1, respectively). Addition of methane did not stimulate incorporation of 15N-nitrogen into biomass, whereas oxygen depletion increased the activity of the nitrogen-fixing community. Analysis of the 16S rRNA genes at the bacterial community level showed a very diverse microbiome that was dominated by Alphaproteobacteria in all sites. Bona fide methane-oxidizing taxa were not very abundant (relative abundance less than 0.1%). Based on our results we conclude that methanotrophs did not contribute significantly to nitrogen fixation in the investigated peatlands.

Nitrosotetrazolium‐Catalyzed Aerobic Oxidation of Alcohols to the Corresponding Carbonyl Compounds

A mesoionic‐nitrosotetrazolium‐catalyzed aerobic oxidation of alcohols is reported. In the presence of catalytic amounts of 5‐nitroso‐1,3‐diphenyltetrazolium tetrafluoroborate (5 mol‐%) and nitric acid (20 mol‐%), a wide range of alcohols are oxidized to the corresponding aldehydes and ketones in yields of 53–100 % at room temperature under ambient air or oxygen conditions. This oxidation shows a strong preference for secondary alcohols over primary alcohols; sterically hindered alcohols are also smoothly oxidized. A mechanism involving a nitroso/NOx catalytic cycle is proposed.

Ecophenotypic responses of benthic foraminifera to oxygen availability along an oxygen gradient in the California Borderland

AbstractSpatial variation in environmental conditions can elicit predictable size and morphological responses in marine organisms through influences on physiology. Thus, spatial and temporal variation in marine organism size and shape are often used to infer paleoenvironmental conditions, such as dissolved oxygen concentrations. Benthic foraminifera commonly serve as a tool for reconstructing past ocean oxygen levels. For example, benthic foraminiferal species assemblages, within‐ and among‐species patterns of test morphology, and geochemical analyses of carbonate tests are often employed to reconstruct past marine conditions. In this study, we measured the sizes and shapes of modern foraminifera representing four species that inhabit a steep oxygen gradient in the Santa Monica Basin on the Southern California Borderland with the aim of quantifying the influence of oxygen availability on foraminiferal morphology, both within and among species. Most foraminifera rely on aerobic respiration, but the four benthic foraminifera from the Santa Monica Basin do not show the predicted size and morphological responses to variations in dissolved oxygen concentrations based on first principles of cell physiology: Bolivina spissa shows no volume or volume‐to‐surface area response, Uvigerina peregrina increases in both test volume and volume‐to‐surface area ratio with decreasing dissolved oxygen concentrations, and both Bolivina argentea and Loxostomum pseudobeyrichi decrease in test volume, but only L. pseudobeyrichi shows a decrease in test volume‐to‐surface area ratio with decreasing oxygen concentrations as expected from physiological predictions. These findings imply that the morphological responses of individual foraminiferal species are not necessarily representative of the responses of other foraminiferal species within the community. Our findings further suggest that these species use physiological strategies such as depressed metabolic rates and alternative energy metabolisms to persist in low oxygen environments and, therefore, cannot be used in any simple way as paleo‐oxygen indicators. Should Proterozoic (1,000–542 million years ago) protists have possessed metabolic strategies similar to foraminifera, the sizes and shapes of protists in the fossil record may not usefully constrain ambient oxygen conditions during the appearance and initial taxonomic radiation of heterotrophic eukaryotes.

A multi-phase micro-kinetic model for simulating aluminum based thermite reactions

This paper presents a hierarchical multiscale approach based on a micro-kinetic model enabling to predict temperature, pressure and species generated during the thermite reaction of Al nanoparticles mixed with CuO nanoparticles. Overall, our phenomenological model integrates and combines series of complex atomistic mechanisms, e.g. diffusion and phase transformation, gas phase reactions and interphase exchange mechanisms, in particular molecular condensation, evaporation and decomposition. Thermodynamics considerations as well as Density Functional Theory (DFT) calculations are used to implement rate equations expressing the complex reactions at solid/liquid/gas interphases. We demonstrate that the model can predict the pressure–time dependence, the different phases and compositions with good accuracy at significantly low computational cost. The influence of Al and CuO particle size, compaction or density, alumina shell thickness and stoichiometry on the pressure and temperature versus time is theoretically predicted with fairly good agreement with available experimental data. A maximum pressure of 47MPa and adiabatic temperature of 3500K are obtained at high compaction, i.e. 50% of the TMD (Theoretical Maximum Density) for stoichiometric mixture, where AlO is shown to be the prevailing gaseous species. At low compaction, we highlight the role of ambient oxygen condition for which the model gives a maximal pressure of 4.2MPa for Al rich mixtures (stoichiometric ratio of 1.2).