Reservoir theory for studying the geochemical evolution of soils

[1] Linking mineral weathering rates measured in the laboratory to those measured at the landscape scale is problematic. In laboratory studies, collections of minerals are exposed to the same weathering environment over a fixed amount of time. In natural soils, minerals enter, are mixed within, and leave the soil via erosion and dissolution/leaching over the course of soil formation. The key to correctly comparing mineral weathering studies from laboratory experiments and field soils is to consistently define time. To do so, we have used reservoir theory. Residence time of a mineral, as defined by reservoir theory, describes the time length between the moment that a mineral enters (via soil production) and leaves (via erosion and dissolution/leaching) the soil. Age of a mineral in a soil describes how long the mineral has been present in the soil. Turnover time describes the time needed to deplete a species of minerals in the soil by sediment efflux from the soil. These measures of time are found to be sensitive to not only sediment flux, which controls the mineral fluxes in and out of a soil, but also internal soil mixing that controls the probability that a mineral survives erosion. When these measures of time are combined with published data suggesting that a mineral’s dissolution reaction rate decreases during the course of weathering, we find that internal soil mixing, by partially controlling the age distribution of minerals within a soil, might significantly alter the soil’s mass loss rate via chemical weathering. Citation: Mudd, S. M., and K. Yoo (2010), Reservoir theory for studying the geochemical evolution of soils, J. Geophys. Res., 115, F03030, doi:10.1029/2009JF001591. 1

The cyanobacterial circadian clock follows midday in vivo and in vitro

Circadian rhythms are biological oscillations that schedule daily changes in physiology. Outside the laboratory, circadian clocks do not generally free-run but are driven by daily cues whose timing varies with the seasons. The principles that determine how circadian clocks align to these external cycles are not well understood. Here, we report experimental platforms for driving the cyanobacterial circadian clock both in vivo and in vitro. We find that the phase of the circadian rhythm follows a simple scaling law in light-dark cycles, tracking midday across conditions with variable day length. The core biochemical oscillator comprised of the Kai proteins behaves similarly when driven by metabolic pulses in vitro, indicating that such dynamics are intrinsic to these proteins. We develop a general mathematical framework based on instantaneous transformation of the clock cycle by external cues, which successfully predicts clock behavior under many cycling environments

Behind the Scenes: Homewood Facilities Operations Staff Yearbook, 2019-2020

Staff yearbook for Johns Hopkins University's Homewood Facilities and Operations, 2019-2020. Funding for the publication was provided by the Office of Diversity and Inclusion's Diversity and Innovation Grant program

Establishing Relevant ADC-based Texture Analysis Metrics for Quantifying Early Treatment-Induced Changes in Head and Neck Squamous Cell Carcinomas

Purpose: The purpose of this study is to identify which texture analysis metrics calculated from apparent diffusion coefficient (ADC) maps from patients with head and neck squamous cell carcinomas (HNSCC) provide quantifiable measures of tumor physiology changes. We discerned which imaging metrics were relevant using baseline agreement and variations during early treatment. Methods: For selective patients with stages II-IV HNSCC, ADC maps were generated from two baselines, taken 1 week apart, and one early treatment scan, obtained during the 2nd week of curative-intent chemoradiation therapy. Regions of interest (ROI), consisting of primary and nodal disease were drawn onto resampled ADC maps. Four 3D texture matrices describing local and regional relationships between voxel intensities in the ROIs were generated. From these, 38 texture metrics and 7 histogram features were calculated for each patient, including the mean and median ADC. Agreement between the two baseline measures was estimated with the intra-class correlation coefficient (ICC). For each metric with an ICC≥0.80, the Wilcoxon signed-rank test was used to test if the difference between the mean of the baselines and the early treatment was non-zero. Results: Texture analysis was implemented on nine patients that had both baselines and early treatment images. Due to baseline agreement, only 9 of the 45 metrics had an ICC ≥0.80, including ADC mean and median. Six of these 9 metrics had a p-value \u3c 0.05. Only 1 of the 9 metrics remained of interest, after applying the Holm correction to the alpha levels: the run length non-uniformity metric (p = 0.004) in the Gray Level Run Length Matrix. Conclusion: The feasibility of texture analysis is dependent on the baseline agreement of each metric, which disqualifies many texture characteristics. However, metrics with high ICC have potential to provide additional quantitative information for the assessment of early treatment changes for HNSCC

Fluid Dynamic Modeling to Support the Development of Flow-Based Hepatocyte Culture Systems for Metabolism Studies

Accurate prediction of metabolism is a significant outstanding challenge in toxicology. The best predictions are based on experimental data from in vitro systems using primary hepatocytes. The predictivity of the primary hepatocyte-based culture systems, however, is still limited due to well-known phenotypic instability and rapid decline of metabolic competence within a few hours. Dynamic flow bioreactors for three-dimensional cell cultures are thought to be better at recapitulating tissue microenvironments and show potential to improve in vivo extrapolations of chemical or drug toxicity based on in vitro test results. These more physiologically relevant culture systems hold potential for extending metabolic competence of primary hepatocyte cultures as well. In this investigation, we used computational fluid dynamics to determine the optimal design of a flow-based hepatocyte culture system for evaluating chemical metabolism in vitro. The main design goals were (1) minimization of shear stress experienced by the cells to maximize viability, (2) rapid establishment of a uniform distribution of test compound in the chamber, and (3) delivery of sufficient oxygen to cells to support aerobic respiration. Two commercially available flow devices – RealBio(®) and QuasiVivo(®) (QV) – and a custom developed fluidized bed bioreactor were simulated, and turbulence, flow characteristics, test compound distribution, oxygen distribution, and cellular oxygen consumption were analyzed. Experimental results from the bioreactors were used to validate the simulation results. Our results indicate that maintaining adequate oxygen supply is the most important factor to the long-term viability of liver bioreactor cultures. Cell density and system flow patterns were the major determinants of local oxygen concentrations. The experimental results closely corresponded to the in silico predictions. Of the three bioreactors examined in this study, we were able to optimize the experimental conditions for long-term hepatocyte cell culture using the QV bioreactor. This system facilitated the use of low system volumes coupled with higher flow rates. This design supports cellular respiration by increasing oxygen concentrations in the vicinity of the cells and facilitates long-term kinetic studies of low clearance test compounds. These two goals were achieved while simultaneously keeping the shear stress experienced by the cells within acceptable limits

Chemical Inhibition of the Mitochondrial Division Dynamin Reveals Its Role in Bax/Bak-Dependent Mitochondrial Outer Membrane Permeabilization

SummaryMitochondrial fusion and division play important roles in the regulation of apoptosis. Mitochondrial fusion proteins attenuate apoptosis by inhibiting release of cytochrome c from mitochondria, in part by controlling cristae structures. Mitochondrial division promotes apoptosis by an unknown mechanism. We addressed how division proteins regulate apoptosis using inhibitors of mitochondrial division identified in a chemical screen. The most efficacious inhibitor, mdivi-1 (for mitochondrial division inhibitor) attenuates mitochondrial division in yeast and mammalian cells by selectively inhibiting the mitochondrial division dynamin. In cells, mdivi-1 retards apoptosis by inhibiting mitochondrial outer membrane permeabilization. In vitro, mdivi-1 potently blocks Bid-activated Bax/Bak-dependent cytochrome c release from mitochondria. These data indicate the mitochondrial division dynamin directly regulates mitochondrial outer membrane permeabilization independent of Drp1-mediated division. Our findings raise the interesting possibility that mdivi-1 represents a class of therapeutics for stroke, myocardial infarction, and neurodegenerative diseases

Vegetation and Topographic Control on Spatial Variability of Soil Organic Carbon

Soil organic carbon (SOC) is one of the most important parameters affecting the hydraulic characteristics of natural soils. Despite being rather easy to measure, SOC is known to be highly variable in space. In this study, vegetation, climate, and morphology factors were used to reproduce the spatial distribution of SOC in the mineral horizons of forest and grassland areas in north-western Italy and the feasibility of the approach was evaluated. When the overall sample (114 samples) was analyzed, average annual rainfall and elevation were significant descriptors of the SOC variability. However, a large part of the variability remains unexplained. Two stratification criteria were then adopted, based on vegetation and topographic properties. We obtained an improvement of the quality of the estimates, particularly for grasslands and forests in the absence of local curvatures. These results indicate that the spatial variability of soil organic matter is scarcely reproducible at the regional scale, unless an a-priori reduction of the heterogeneity is applied. A discussion on the feasibility of applying stratification criteria to deal with heterogeneous samples closes the pape

High Response Rate With Extended Dosing of Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma

BACKGROUND: Cemiplimab (Libtayo METHODS: In this open-label, phase II trial (ClinicalTrials.gov identifier NCT02760498), the cohort of patients ≥18 years old with advanced CSCC received cemiplimab 600 mg intravenously Q4W for up to 48 weeks. Tumor measurements were recorded every 8 weeks. The primary endpoint was objective response rate by independent central review. RESULTS: Sixty-three patients with advanced CSCC were treated with cemiplimab. The median duration of follow-up was 22.4 months (range: 1.0-39.8). An objective response was observed in 39 patients (62%; 95% CI: 48.8% to 73.9%), with 22% of patients (n CONCLUSIONS: Extended dosing of cemiplimab 600 mg intravenously Q4W exhibited substantial antitumor activity, rapid and durable responses, and an acceptable safety profile in patients with advanced CSCC. These results confirm that cemiplimab is a highly active therapy for advanced CSCC. Additional data would help ascertain the benefit-risk profile for the 600 mg intravenous dosing regimen compared with the approved regimen