Explaining the unexplainable: leveraging extremal dependence to characterize the 2021 Pacific Northwest heatwave

In late June, 2021, a devastating heatwave affected the US Pacific Northwest and western Canada, breaking numerous all-time temperature records by large margins and directly causing hundreds of fatalities. The observed 2021 daily maximum temperature across much of the U.S. Pacific Northwest exceeded upper bound estimates obtained from single-station temperature records even after accounting for anthropogenic climate change, meaning that the event could not have been predicted under standard univariate extreme value analysis assumptions. In this work, we utilize a flexible spatial extremes model that considers all stations across the Pacific Northwest domain and accounts for the fact that many stations simultaneously experience extreme temperatures. Our analysis incorporates the effects of anthropogenic forcing and natural climate variability in order to better characterize time-varying changes in the distribution of daily temperature extremes. We show that greenhouse gas forcing, drought conditions and large-scale atmospheric modes of variability all have significant impact on summertime maximum temperatures in this region. Our model represents a significant improvement over corresponding single-station analysis, and our posterior medians of the upper bounds are able to anticipate more than 96% of the observed 2021 high station temperatures after properly accounting for extremal dependence.Comment: 19 pages, 4 figures and 2 table

Nighttime chemistry at a high altitude site above Hong Kong

Nighttime reactions of nitrogen oxides influence ozone, volatile organic compounds, and aerosol and are thus important to the understanding of regional air quality. Despite large emissions and rapid recent growth of nitrogen oxide concentrations, there are few studies of nighttime chemistry in China. Here we present measurements of nighttime nitrogen oxides, NO3 and N2O5, from a coastal mountaintop site in Hong Kong adjacent to the megacities of the Pearl River Delta region. This is the first study of nighttime chemistry from a site within the residual layer in China. Key findings include the following. First, highly concentrated urban NOx outflow from the Pearl River Delta region was sampled infrequently at night, with N2O5 mixing ratios up to 8 ppbv (1 min average) or 12 ppbv (1 s average) in nighttime aged air masses. Second, the average N2O5 uptake coefficient was determined from a best fit to the available steady state lifetime data as γ(N2O5) = 0.014 ± 0.007. Although this determination is uncertain due to the difficulty of separating N2O5 losses from those of NO3, this value is in the range of previous residual layer determinations of N2O5 uptake coefficients in polluted air in North America. Third, there was a significant contribution of biogenic hydrocarbons to NO3 loss inferred from canister samples taken during daytime. Finally, daytime N2O5 mixing ratios were in accord with their predicted photochemical steady state. Heterogeneous uptake of N2O5 in fog is determined to be an important production mechanism for soluble nitrate, even during daytime. Key Points Large (up to 12 ppbv N2O5) but infrequent nocturnal NOx outflow from the Pearl River Delta Average N2O5 uptake coefficients 0.014 ± 0.007, in line with residual layer measurements in the U.S. Daytime N2O5 follows predicted steady state but rapidly produces soluble nitrate in fog.Department of Civil and Environmental Engineerin

AN ONBOARD HYDROGEN GENERATION METHOD BASED ON HYDRIDES AND WATER RECOVERY FOR MICRO-FUEL CELLS

poster abstractThe purpose of this paper is to conduct experiments to generate hydrogen in a fuel cell by employing hydrides and water recovery methods. Micro-proton exchange membrane fuel cells are the next generation power source for micro-scale applications. The methods presented in the paper make use of the recycled water produced from the cathode reaction to develop high energy density micro fuel cells. The method for this experiment is accomplished by utilizing oxidation-reduction reactions that take place in the cell. These reactants must be constantly replenished through an external source. This paper will introduce the methods and procedures that permit a solution to the small-scale generation of fuel and water byproduct; this is accomplished by implementing a water recovery mechanism. The experiment commenced with designing and manufacturing a Nafion membrane and a fuel cell package. From then the calcium hydride and lithium aluminum hydride was loaded. These hydrides were given controlled amounts of water vapor and the amount of gas production was measured. After the amount of gas is measured, we are able to calculate the most efficient way to receive the greatest amount of hydrogen from the cell. The objective of our experiment is to achieve a higher energy density for micro-fuel cells. Our aim is that the results of our research will replace lithium ion batteries with a high energy density fuel cell that can increase longevity as a source, and is able to be used in multiple environments including pace makers and space exploration. Multidisciplinary Undergraduate Research Institute, CRL Program

DEVELOPMENT OF A MICROFLUIDIC GAS GENERATOR FROM AN EFFICIENT FILM-BASED MICROFABRICATION METHOD

poster abstractRecently, tape&film based microfabrication method has been studied for rapid prototyping of microfluidic devices due to its low cost and ease of fabrication [1]. But most of the reported film-based microfluidic devices are simple single-layer patterned 2-dimentional (2D) designs, whose potential applications are limited. In this paper, we present the design, fabrication and testing results of a 3-dimentional (3D) structured microfluidic gas generator prototype. This gas generator is used as an example to introduce our new approach of film-based fabrication method towards lab-use microfluidic research, which usually requires constant change of design and prefers low fabrication cost and short fabrication period. The prototype is a film-based comprehensive microfluidic gas generator which integrates self-circulation, self-regulation, catalytic reaction, and gas/liquid separation. Time and economy efficiency are the biggest merit of this method. The only required facility during the whole process is a digital craft-cutter. The working principle of the device is illustrated in Fig.1 [2]. The film-based prototype is an alternate version of the silicon-based self-circulating self-regulating gas generator developed by Meng [2]. Fig.2 shows the schematic of the filmbased prototype. It consists of 15 layers of films, tapes, glass slide, tubing connectors, and cube supporting. As shown in Fig.3, the prototype device was obtained by sequentially aligning and stacking multiple layers of patterned films and double-sided Kapton tape. The patterns were obtained by a digital craft-cutter from CAD drawings. The 3D structure was made from both the pattern and the thickness of the layer material, as shown in Fig.4. Besides, functional features can be easily added into the device. For instance, Pt-black was partially sprayed on the tape layer for catalytic reaction using a shadow mask, and nanoporous membrane was cut in the desired shape and stack-placed in position as the gas/liquid separator. The self-circulating and self-regulating functions were achieved by capillary force difference in different channels as shown in Fig.4, which can be achieved by fabricating different channel depths and treating the surface of certain channel into hydrophilic and leave others hydrophobic. The treatment for polystyrene (PS) film was achieved by spraying Lotus Leaf® hydrophilic coating or using oxygen plasma machine [3]. The fabricated device was tested with H2O2 solutions (for O2) and NH3BH3 solutions (for H2) at different concentrations (Fig.5). A pressure difference (1 psi) was applied across the gas/liquid separation membrane to provide better venting. The gas generation profiles are shown in Fig.6 and the summarized characteristics is given in Table 1. The generated gas flow rate is measured by a gas flow meter, and liquid pumping rate measured by monitoring the movement of a liquid/gas meniscus. Fig. 6 shows that higher reactant concentration causes higher gas generation rate. The fluctuation of gas generation rate is due to the pulsatile pumping of this self-pumping mechanism. It is expected that designs with multiple parallel channels can make the gas generation profile smooth due to the interactions among the channels. Detailed characterization results and discussion on reaction kinetics and pumping dynamics in the microfluidic reactor will be reported

A numerical framework for interstitial fluid pressure imaging in poroelastic MRE

A numerical framework for interstitial fluid pressure imaging (IFPI) in biphasic materials is investigated based on three-dimensional nonlinear finite element poroelastic inversion. The objective is to reconstruct the time-harmonic pore-pressure field from tissue excitation in addition to the elastic parameters commonly associated with magnetic resonance elastography (MRE). The unknown pressure boundary conditions (PBCs) are estimated using the available full-volume displacement data from MRE. A subzone-based nonlinear inversion (NLI) technique is then used to update mechanical and hydrodynamical properties, given the appropriate subzone PBCs, by solving a pressure forward problem (PFP). The algorithm was evaluated on a single-inclusion phantom in which the elastic property and hydraulic conductivity images were recovered. Pressure field and material property estimates had spatial distributions reflecting their true counterparts in the phantom geometry with RMS errors around 20% for cases with 5% noise, but degraded significantly in both spatial distribution and property values for noise levels > 10%. When both shear moduli and hydraulic conductivity were estimated along with the pressure field, property value error rates were as high as 58%, 85% and 32% for the three quantities, respectively, and their spatial distributions were more distorted. Opportunities for improving the algorithm are discussed

Identification of BC005512 as a DNA Damage Responsive Murine Endogenous Retrovirus of GLN Family Involved in Cell Growth Regulation

Genotoxicity assessment is of great significance in drug safety evaluation, and microarray is a useful tool widely used to identify genotoxic stress responsive genes. In the present work, by using oligonucleotide microarray in an in vivo model, we identified an unknown gene BC005512 (abbreviated as BC, official full name: cDNA sequence BC005512), whose expression in mouse liver was specifically induced by seven well-known genotoxins (GTXs), but not by non-genotoxins (NGTXs). Bioinformatics revealed that BC was a member of the GLN family of murine endogenous retrovirus (ERV). However, the relationship to genotoxicity and the cellular function of GLN are largely unknown. Using NIH/3T3 cells as an in vitro model system and quantitative real-time PCR, BC expression was specifically induced by another seven GTXs, covering diverse genotoxicity mechanisms. Additionally, dose-response and linear regression analysis showed that expression level of BC in NIH/3T3 cells strongly correlated with DNA damage, measured using the alkaline comet assay,. While in p53 deficient L5178Y cells, GTXs could not induce BC expression. Further functional studies using RNA interference revealed that down-regulation of BC expression induced G1/S phase arrest, inhibited cell proliferation and thus suppressed cell growth in NIH/3T3 cells. Together, our results provide the first evidence that BC005512, a member from GLN family of murine ERV, was responsive to DNA damage and involved in cell growth regulation. These findings could be of great value in genotoxicity predictions and contribute to a deeper understanding of GLN biological functions

CD27− B-Cells Produce Class Switched and Somatically Hyper-Mutated Antibodies during Chronic HIV-1 Infection

Class switch recombination and somatic hypermutation occur in mature B-cells in response to antigen stimulation. These processes are crucial for the generation of functional antibodies. During HIV-1 infection, loss of memory B-cells, together with an altered differentiation of naïve B-cells result in production of low quality antibodies, which may be due to impaired immunoglobulin affinity maturation. In the current study, we evaluated the effect of HIV-1 infection on class switch recombination and somatic hypermutation by studying the expression of activation-induced cytidine deaminase (AID) in peripheral B-cells from a cohort of chronically HIV-1 infected patients as compared to a group of healthy controls. In parallel, we also characterized the phenotype of B-cells and their ability to produce immunoglobulins in vitro. Cells from HIV-1 infected patients showed higher baseline levels of AID expression and increased IgA production measured ex-vivo and upon CD40 and TLR9 stimulation in vitro. Moreover, the percentage of CD27−IgA+ and CD27−IgG+ B-cells in blood was significantly increased in HIV-1 infected patients as compared to controls. Interestingly, our results showed a significantly increased number of somatic hypermutations in the VH genes in CD27− cells from patients. Taken together, these results show that during HIV-1 infection, CD27− B-cells can also produce class switched and somatically hypermutated antibodies. Our data add important information for the understanding of the mechanisms underlying the loss of specific antibody production observed during HIV-1 infection

A Regulatory Role for NBS1 in Strand-Specific Mutagenesis during Somatic Hypermutation

Activation-induced cytidine deaminase (AID) is believed to initiate somatic hypermutation (SHM) by deamination of deoxycytidines to deoxyuridines within the immunoglobulin variable regions genes. The deaminated bases can subsequently be replicated over, processed by base excision repair or mismatch repair, leading to introduction of different types of point mutations (G/C transitions, G/C transversions and A/T mutations). It is evident that the base excision repair pathway is largely dependent on uracil-DNA glycosylase (UNG) through its uracil excision activity. It is not known, however, which endonuclease acts in the step immediately downstream of UNG, i.e. that cleaves at the abasic sites generated by the latter. Two candidates have been proposed, an apurinic/apyrimidinic endonuclease (APE) and the Mre11-Rad50-NBS1 complex. The latter is intriguing as this might explain how the mutagenic pathway is primed during SHM. We have investigated the latter possibility by studying the in vivo SHM pattern in B cells from ataxia-telangiectasia-like disorder (Mre11 deficient) and Nijmegen breakage syndrome (NBS1 deficient) patients. Our results show that, although the pattern of mutations in the variable heavy chain (VH) genes was altered in NBS1 deficient patients, with a significantly increased number of G (but not C) transversions occurring in the SHM and/or AID targeting hotspots, the general pattern of mutations in the VH genes in Mre11 deficient patients was only slightly altered, with an increased frequency of A to C transversions. The Mre11-Rad50-NBS1 complex is thus unlikely to be the major nuclease involved in cleavage of the abasic sites during SHM, whereas NBS1 might have a specific role in regulating the strand-biased repair during phase Ib mutagenesis