Investigating the observed sensitivities of air-quality extremes to meteorological drivers via quantile regression

Air pollution variability is strongly dependent on meteorology. However, quantifying the impacts of changes in regional climatology on pollution extremes can be difficult due to the many non-linear and competing meteorological influences on the production, transport, and removal of pollutant species. Furthermore, observed pollutant levels at many sites show sensitivities at the extremes that differ from those of the overall mean, indicating relationships that would be poorly characterized by simple linear regressions. To address this challenge, we apply quantile regression to observed daily ozone (O[subscript 3]) and fine particulate matter (PM[subscript 2.5]) levels and reanalysis meteorological fields in the USA over the past decade to specifically identify the meteorological sensitivities of higher pollutant levels. From an initial set of over 1700 possible meteorological indicators (including 28 meteorological variables with 63 different temporal options), we generate reduced sets of O[subscript 3] and PM[subscript 2.5] indicators for both summer and winter months, analyzing pollutant sensitivities to each for response quantiles ranging from 2 to 98 %. Primary covariates connected to high-quantile O[subscript 3] levels include temperature and relative humidity in the summer, while winter O[subscript 3] levels are most commonly associated with incoming radiation flux. Covariates associated with summer PM[subscript 2.5] include temperature, wind speed, and tropospheric stability at many locations, while stability, humidity, and planetary boundary layer height are the key covariates most frequently associated with winter PM[subscript 2.5]. We find key differences in covariate sensitivities across regions and quantiles. For example, we find nationally averaged sensitivities of 95th percentile summer O[subscript 3] to changes in maximum daily temperature of approximately 0.9 ppb °C[superscript −1], while the sensitivity of 50th percentile summer O[subscript 3] (the annual median) is only 0.6 ppb °C[superscript −1]. This gap points to differing sensitivities within various percentiles of the pollutant distribution, highlighting the need for statistical tools capable of identifying meteorological impacts across the entire response spectrum.United States. Environmental Protection Agency (Grant/Cooperative Agreement RD-83522801

Microstructural strain energy of α-uranium determined by calorimetry and neutron diffractometry

The microstructural contribution to the heat capacity of α-uranium was determined by measuring the heat-capacity difference between polycrystalline and single-crystal samples from 77 to 320 K. When cooled to 77 K and then heated to about 280 K, the uranium microstructure released (3±1) J/mol of strain energy. On further heating to 300 K, the microstructure absorbed energy as it began to redevelop microstrains. Anisotropic strain-broadening parameters were extracted from neutron-diffraction measurements on polycrystals. Combining the strain-broadening parameters with anisotropic elastic constants from the literature, the microstructural strain energy is predicted in the two limiting cases of statistically isotropic stress and statistically isotropic strain. The result calculated in the limit of statistically isotropic stress was (3.7±0.5) J/mol K at 77 K and (1±0.5) J/mol at room temperature. In the limit of statistically isotropic strain, the values were (7.8±0.5) J/mol K at 77 K and (4.5±0.5) J/mol at room temperature. In both cases the changes in the microstructural strain energy showed good agreement with the calorimetry

Magnetic polarons and magnetoresistance in EuB6

EuB6 is a low carrier density ferromagnet which exhibits large magnetoresistance, positive or negative depending on temperature. The formation of magnetic polarons just above the magnetic critical temperature has been suggested by spin-flip Raman scattering experiments. We find that the fact that EuB6 is a semimetal has to be taken into account to explain its electronic properties, including magnetic polarons and magnetoresistance.Comment: 6 pages, 1 figur

Broadly Applicable Methodology for the Rapid and Dosable Small Molecule-Mediated Regulation of Transcription Factors in Human Cells

Direct and selective small molecule control of transcription factor activity is an appealing avenue for elucidating the cell biology mediated by transcriptional programs. However, pharmacologic tools to modulate transcription factor activity are scarce because transcription factors are not readily amenable to small molecule-mediated regulation. Moreover, existing genetic approaches to regulate transcription factors often lead to high nonphysiologic levels of transcriptional activation that significantly impair our ability to understand the functional implications of transcription factor activity. Herein, we demonstrate that small molecule-mediated conformational control of protein degradation is a generally applicable, chemical biological methodology to obtain small molecule-regulated transcription factors that modulate transcriptional responses at physiologic levels in human cells. Our establishment of this approach allows for the rapid development of genetically encoded, small molecule-regulated transcription factors to explore the biologic and therapeutic impact of physiologic levels of transcription factor activity in cells

Tricritical Phenomena at the Cerium γ→α\gamma \to \alpha Transition

The $\gamma \to \alpha$ isostructural transition in the Ce$_{0.9-x}$La$_x$Th$_{0.1}$ system is measured as a function of La alloying using specific heat, magnetic susceptibility, resistivity, thermal expansivity/striction measurements. A line of discontinuous transitions, as indicated by the change in volume, decreases exponentially from 118 K to close to zero with increasing La doping and the transition changes from being first-order to continuous at a critical concentration $0.10 \leq x_c \leq 0.14$. At the tricritical point, the coefficient of the linear $T$ term in the specific heat $\gamma$ and the magnetic susceptibility start to increase rapidly near $x$ = 0.14 and gradually approaches large values at $x$=0.35 signifying that a heavy Fermi-liquid state evolves at large doping. Near $x_c$, the Wilson ratio, $R_W$, has a value of 3.0, signifying the presence of magnetic fluctuations. Also, the low-temperature resistivity shows that the character of the low-temperature Fermi-liquid is changing

One-to-one full scale simulations of laser wakefield acceleration using QuickPIC

We use the quasi-static particle-in-cell code QuickPIC to perform full-scale, one-to-one LWFA numerical experiments, with parameters that closely follow current experimental conditions. The propagation of state-of-the-art laser pulses in both preformed and uniform plasma channels is examined. We show that the presence of the channel is important whenever the laser self-modulations do not dominate the propagation. We examine the acceleration of an externally injected electron beam in the wake generated by 10 J laser pulses, showing that by using ten-centimeter-scale plasma channels it is possible to accelerate electrons to more than 4 GeV. A comparison between QuickPIC and 2D OSIRIS is provided. Good qualitative agreement between the two codes is found, but the 2D full PIC simulations fail to predict the correct laser and wakefield amplitudes.Comment: 5 pages, 5 figures, accepted for publication IEEE TPS, Special Issue - Laser & Plasma Accelerators - 8/200

Unfolded Protein Response Activation Reduces Secretion and Extracellular Aggregation of Amyloidogenic Immunoglobulin Light Chain

Light-chain amyloidosis (AL) is a degenerative disease characterized by the extracellular aggregation of a destabilized amyloidogenic Ig light chain (LC) secreted from a clonally expanded plasma cell. Current treatments for AL revolve around ablating the cancer plasma cell population using chemotherapy regimens. Unfortunately, this approach is limited to the ∼70% of patients who do not exhibit significant organ proteotoxicity and can tolerate chemotherapy. Thus, identifying new therapeutic strategies to alleviate LC organ proteotoxicity should allow AL patients with significant cardiac and/or renal involvement to subsequently tolerate established chemotherapy treatments. Using a small-molecule screening approach, the unfolded protein response (UPR) was identified as a cellular signaling pathway whose activation selectively attenuates secretion of amyloidogenic LC, while not affecting secretion of a nonamyloidogenic LC. Activation of the UPR-associated transcription factors XBP1s and/or ATF6 in the absence of stress recapitulates the selective decrease in amyloidogenic LC secretion by remodeling the endoplasmic reticulum proteostasis network. Stress-independent activation of XBP1s, or especially ATF6, also attenuates extracellular aggregation of amyloidogenic LC into soluble aggregates. Collectively, our results show that stress-independent activation of these adaptive UPR transcription factors offers a therapeutic strategy to reduce proteotoxicity associated with LC aggregation

Enteropathogen antibody dynamics and force of infection among children in low-resource settings.

Little is known about enteropathogen seroepidemiology among children in low-resource settings. We measured serological IgG responses to eight enteropathogens (Giardia intestinalis, Cryptosporidium parvum, Entamoeba histolytica, Salmonella enterica, enterotoxigenic Escherichia coli, Vibrio cholerae, Campylobacter jejuni, norovirus) in cohorts from Haiti, Kenya, and Tanzania. We studied antibody dynamics and force of infection across pathogens and cohorts. Enteropathogens shared common seroepidemiologic features that enabled between-pathogen comparisons of transmission. Overall, exposure was intense: for most pathogens the window of primary infection was <3 years old; for highest transmission pathogens primary infection occurred within the first year. Longitudinal profiles demonstrated significant IgG boosting and waning above seropositivity cutoffs, underscoring the value of longitudinal designs to estimate force of infection. Seroprevalence and force of infection were rank-preserving across pathogens, illustrating the measures provide similar information about transmission heterogeneity. Our findings suggest antibody response can be used to measure population-level transmission of diverse enteropathogens in serologic surveillance

Oligocarbonate Molecular Transporters: Oligomerization-Based Syntheses and Cell-Penetrating Studies

A new family of guanidinium-rich molecular transporters featuring a novel oligocarbonate backbone with 1,7-side chain spacing is described. Conjugates can be rapidly assembled irrespective of length in a one-step oligomerization strategy that can proceed with concomitant introduction of probes (or by analogy drugs). The new transporters exhibit excellent cellular entry as determined by flow cytometry and fluorescence microscopy, and the functionality of their drug delivery capabilities was confirmed by the delivery of the bioluminescent small molecule probe luciferin and turnover by its intracellular target enzyme