Investigating Sources of Variability and Error in Simulations of Carbon Dioxide in an Urban Region

Greenhouse gas (GHG) emissions estimation methods that use atmospheric trace gas observations, including inverse modeling techniques, perform better when carbon dioxide (CO2) fluxes are more accurately transported and dispersed in the atmosphere by a numerical model. In urban areas, transport and dispersion is particularly difficult to simulate using current mesoscale meteorological models due, in part, to added complexity from surface heterogeneity and fine spatial/temporal scales. It is generally assumed that the errors in GHG estimation methods in urban areas are dominated by errors in transport and dispersion. Other significant errors include, but are not limited to, those from assumed emissions magnitude and spatial distribution. To assess the predictability of simulated trace gas mole fractions in urban observing systems using a numerical weather prediction model, we employ an Eulerian model that combines traditional meteorological variables with multiple passive tracers of atmospheric CO2 from anthropogenic inventories and a biospheric model. The predictability of the Eulerian model is assessed by comparing simulated atmospheric CO2 mole fractions to observations from four in situ tower sites (three urban and one rural) in the Washington DC/Baltimore, MD area for February 2016. Four different gridded fossil fuel emissions inventories along with a biospheric flux model are used to create an ensemble of simulated atmospheric CO2 observations within the model. These ensembles help to evaluate whether the modeled observations are impacted more by the underlying emissions or transport. The spread of modeled observations using the four emission fields indicates the model's ability to distinguish between the different inventories under various meteorological conditions. Overall, the Eulerian model performs well; simulated and observed average CO2 mole fractions agree within 1% when averaged at the three urban sites across the month. However, there can be differences greater than 10% at any given hour, which are attributed to complex meteorological conditions rather than differences in the inventories themselves. On average, the mean absolute error of the simulated compared to actual observations is generally twice as large as the standard deviation of the modeled mole fractions across the four emission inventories. This result supports the assumption, in urban domains, that the predicted mole fraction error relative to observations is dominated by errors in model meteorology rather than errors in the underlying fluxes in winter months. As such, minimizing errors associated with atmospheric transport and dispersion may help improve the performance of GHG estimation models more so than improving flux priors in the winter months. We also find that the errors associated with atmospheric transport in urban domains are not restricted to certain times of day. This suggests that atmospheric inversions should use CO2 observations that have been filtered using meteorological observations rather than assuming that meteorological modeling is most accurate at certain times of day (such as using only mid-afternoon observations)

Trimethoprim‐Sulfamethoxazole Activity and Pharmacodynamics against Glycopeptide‐Intermediate Staphylococcus aureus

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90392/1/phco.22.12.983.33599.pd

Terrain Features and Architecture of Wolverine (Gulo gulo) Resting Burrows and Reproductive Dens on Arctic Tundra

Burrowing species rely on subterranean and subnivean sites to fulfill important life-history and behavioral processes, including predator avoidance, thermoregulation, resting, and reproduction. For these species, burrow architecture can affect the quality and success of such processes, since characteristics like tunnel width and chamber depth influence access by predators, thermal insulation, and energy spent digging. Wolverines (Gulo gulo) living in Arctic tundra environments dig burrows in snow during winter for resting sites and reproductive dens, but there are few published descriptions of such burrows. We visited 114 resting burrows and describe associated architectural characteristics and non-snow structure. Additionally, we describe characteristics of 15 reproductive den sites that we visited during winter and summer. Although many resting burrows were solely excavated in snow, most incorporated terrain structures including cliffs, talus, river shelf ice, thermokarst caves, and stream cutbanks. Burrows typically consisted of a single tunnel leading to a single chamber, though some burrows had multiple entrances, branching tunnels, or both. Tunnels in resting burrows were shorter than those in reproductive dens, and resting chambers were typically located at the deepest part of the burrow. Reproductive dens were associated with snowdrift-forming terrain features such as streambeds, cutbanks on lake edges, thermokarst caves, and boulders. Understanding such characteristics of Arctic wolverine resting and reproductive structures is critical for assessing anthropogenic impacts as snowpack undergoes climate-driven shifts.Les espèces fouisseuses dépendent de lieux enfouis sous la terre et sous la neige pour satisfaire leurs importants processus de vie et de comportement, y compris l’évitement des prédateurs, la thermorégulation, le repos et la reproduction. Pour ces espèces, l’architecture des terriers peut avoir des effets sur la qualité et la réussite des processus, car des caractéristiques comme la largeur des tunnels et la profondeur des chambres influencent l’accès aux terriers par les prédateurs, l’isolation thermique et l’énergie dépensée pour creuser. L’hiver, les carcajous (Gulo gulo) qui vivent dans les environnements de la toundra de l’Arctique creusent des terriers dans la neige afin de s’en servir comme aires de repos et comme tanières de reproduction. Cependant, peu de descriptions de tels terriers ont été publiées. Nous avons visité 114 terriers de repos, puis nous avons décrit leurs caractéristiques architecturales et les structures connexes n’étant pas recouvertes de neige. Par ailleurs, nous décrivons les caractéristiques de 15 tanières de reproduction que nous avons visitées en hiver et en été. Même si de nombreux terriers de repos ont été uniquement creusés dans la neige, la plupart des terriers incorporaient des structures topographiques, dont des falaises, des talus, de la glace de banquise, des grottes thermokarstiques et des hautes berges de cours d’eau. En général, les terriers étaient composés d’un seul tunnel menant à une seule chambre, bien que certains avaient plusieurs entrées, des galeries, ou les deux. Les tunnels des aires de repos étaient moins longs que ceux des tanières de reproduction, et les chambres de repos étaient généralement situées dans la partie la plus profonde des terriers. Les tanières de reproduction étaient installées dans des caractéristiques topographiques où s’amoncelle la neige, comme les lits de cours d’eau, les hautes berges de lacs, les grottes thermokarstiques et les rochers. Il est essentiel de comprendre les caractéristiques des structures de repos et de reproduction des carcajous de l’Arctique afin d’être en mesure d’évaluer les incidences anthropiques au moment où le manteau neigeux subit des changements liés au climat

Host Stage Structure and Baculovirus Transmission in Mamestra brassicae L. (Lepidoptera: Noctuidae) Larvae: a Laboratory Examination of Small Scale Epizootics

ABSTRACT -The effects of stage structure and host density on baculovirus horizontal transmission were examined in the laboratory using larvae of the cabbage moth, Mamestra brassicae L. (Lepidoptera: Noctuidae). Insects were reared at three instar combinations and three host densities in closed containers with infected larvae. Insects were observed daily and the number of deaths and time to death were recorded. Levels of virus mortality were marginally higher in the containers where a higher density of hosts was introduced. Larvae appeared to have a greater risk of infection when late instar combinations were used. Final levels of mortality of older larvae were significantly higher than those of younger larvae. Mean times to death of larval populations were longer for larvae at earlier instar combinations, with a faster decrease in survivorship of older larvae over time

Acute B-Cell Inhibition by Soluble Antigen Arrays Is Valency-Dependent and Predicts Immunomodulation in Splenocytes

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biomacromolecules, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.biomac.9b00328.Antigen valency plays a fundamental role in directing the nature of an immune response to be stimulatory or tolerogenic. Soluble Antigen Arrays (SAgAs) are an antigen-specific immunotherapy that combats autoimmunity through the multivalent display of autoantigen. While mechanistic studies have shown SAgAs to induce T and B-cell anergy, the effect of SAgA valency has never been experimentally tested. Here, SAgAs of discrete antigen valencies were synthesized by click chemistry and evaluated for acute B-cell signaling inhibition as well as downstream immunomodulatory effects in splenocytes. Initial studies using the Raji B-cell line demonstrated SAgA valency dictated the extent of calcium flux. Lower valency constructs elicited the largest reductions in B-cell activation. In splenocytes from mice with experimental autoimmune encephalomyelitis, the same valency-dependent effects were evident in the downregulation of the costimulatory marker CD86. The reduction of calcium flux observed in Raji B-cells correlated strongly with downregulation in splenocyte CD86 expression after 72 hours. Here, a thorough analysis of SAgA antigenic valency illustrates that low, but not monovalent, presentation of autoantigen was ideal for eliciting the most potent immunomodulatory effects.Madison and Lila Self Graduate Fellowship at the University of KansasNIH T32 GM00854

Biogeochemical Consequences of Rapid Microbial Turnover and Seasonal Succession in Soil

Soil microbial communities have the metabolic and genetic capability to adapt to changing environmental conditions on very short time scales. In this paper we combine biogeochemical and molecular approaches to reveal this potential, showing that microbial biomass can turn over on time scales of days to months in soil, resulting in a succession of microbial communities over the course of a year. This new understanding of the year-round turnover and succession of microbial communities allows us for the first time to propose a temporally explicit N cycle that provides mechanistic hypotheses to explain both the loss and retention of dissolved organic N (DON) and inorganic N (DIN) throughout the year in terrestrial ecosystems. In addition, our results strongly support the hypothesis that turnover of the microbial community is the largest source of DON and DIN for plant uptake during the plant growing season. While this model of microbial biogeochemistry is derived from observed dynamics in the alpine, we present several examples from other ecosystems to indicate that the general ideas of biogeochemical fluxes being linked to turnover and succession of microbial communities are applicable to a wide range of terrestrial ecosystems

Soluble Antigen Arrays for Selective Desensitization of Insulin-Reactive B Cells

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.molpharmaceut.8b01250.Autoimmune diseases are believed to be highly dependent on loss of immune tolerance to self-antigens. Currently, no treatments have been successful clinically in inducing autoantigen-specific tolerance, including efforts to utilize antigen-specific immunotherapy (ASIT) to selectively correct the aberrant autoimmunity. Soluble antigen arrays (SAgAs) represent a novel autoantigen delivery system composed of a linear polymer, hyaluronic acid (HA), displaying multiple copies of conjugated autoantigen. We have previously reported that Soluble Antigen Arrays proteolipid protein (SAgAPLP) induced tolerance to a specific multiple sclerosis (MS) autoantigen, proteolipid peptide (PLP). Utilizing SAgA technology, we have developed a new ASIT as a possible type 1 diabetes (T1D) therapeutic by conjugating human insulin to HA, known as Soluble Antigen Array Insulin (SAgAIns). Three types were synthesized: low valency lvSAgAIns (2 insulins per HA), medium valency mvSAgAIns (4 insulins per HA) and, high valency hvSAgAIns (9 insulins per HA) to determine if valency differentially modulates the ex vivo activity of insulin-binding B cells (IBCs). Extensive biophysical characterization was performed for the SAgA molecules. SAgAIns molecules were successfully used to affect the biologic activity of IBCs by inducing desensitization of the B cell antigen receptors (BCR). SAgAIns bound specifically to insulin-reactive B cells without blocking epitopes recognized by antibodies against the Fc regions of membrane immunoglobulin or CD79 transducer components of the BCR. Pre-incubation of IBCs (125Tg) with SAgAIns, but not HA alone, rendered the IBCs refractory to re-stimulation. SAgAIns induced a decrease in BCR expression and IP3R-mediated intracellular calcium release. Surprisingly, SAgAIns binding to BCR on the surface of IBCs induced the observed effects at both high and low SAgAIns valency. Future studies aim to test the effects of SAgAIns on disease progression in the VH125.NOD mouse model of T1D.NIH T32 GM00854

Assessment of Field Experience Related to Pressurized Water Reactor Primary System Leaks

This paper presents our assessment of field experience related to pressurized water reactor (PWR) primary system leaks in terms of their number and rates, how aging affects frequency of leak events, the safety significance of such leaks, industry efforts to reduce leaks, and effectiveness of current leak detection systems. We have reviewed the licensee event reports to identify the events that took place during 1985 to the third quarter of 1996, and reviewed related technical literature and visited PWR plants to analyze these events. Our assessment shows that USNRC licensees have taken effective actions to reduce the number of leak events. One main reason for this decreasing trend was the elimination or reportable leakages from valve stem packing after 1991. Our review of leak events related to vibratory fatigue reveals a statistically significant decreasing trend with age (years of operation), but not in calendar time. Our assessment of worldwide data on leakage caused by thermal fatigue cracking is that the fatigue of aging piping is a safety significant issue. Our review of leak events has identified several susceptible sites in piping having high safety significance; but the inspection of some of these sites is not required by the ASME Code. These sites may be included in the risk-informed inspection programs

Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation

BACKGROUND: Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in part are responsible for tissue damage during disease progression. Thus, we hypothesized that a MMP-9/-12 generated fragment of elastin may be a relevant biochemical maker for lung diseases. METHODS: Elastin fragments were identified by mass-spectrometry and one sequence, generated by MMP-9 and -12 (ELN-441), was selected for monoclonal antibody generation and used in the development of an ELISA. Soluble and insoluble elastin from lung was cleaved in vitro and the time-dependent release of fragments was assessed in the ELN-441 assay. The release of ELN-441 in human serum from patients with chronic obstructive pulmonary disease (COPD) (n = 10) and idiopathic pulmonary fibrosis (IPF) (n = 29) were compared to healthy matched controls (n = 11). RESULTS: The sequence ELN-441 was exclusively generated by MMP-9 and -12 and was time-dependently released from soluble lung elastin. ELN-441 levels were 287% higher in patients diagnosed with COPD (p < 0.001) and 124% higher in IPF patients (p < 0.0001) compared with controls. ELN-441 had better diagnostic value in COPD patients (AUC 97%, p = 0.001) than in IPF patients (AUC 90%, p = 0.0001). The odds ratios for differentiating controls from COPD or IPF were 24 [2.06–280] for COPD and 50 [2.64–934] for IPF. CONCLUSIONS: MMP-9 and -12 time-dependently released the ELN-441 epitope from elastin. This fragment was elevated in serum from patients with the lung diseases IPF and COPD, however these data needs to be validated in larger clinical settings