Vegetation alters urban climates via transpirational cooling; however, unlike shorter vegetation, trees additionally provide shade and shelter. Urban canopy models (UCMs) are coupled with mesoscale ...models for assessment of neighbourhood-scale climate, but their representation of urban trees is limited. We present BEP-Tree, a multi-layer UCM that integrates trees instead of using the ‘tile’ approach that characterizes most urban mesoscale modelling. BEP-Tree resolves the microclimate underneath trees where outdoor human thermal exposure occurs; these conditions are largely inaccessible to current mesoscale modelling and remote sensing approaches. Moreover, BEP-Tree allows trees to protrude above buildings, enabling assessment of low-rise neighbourhoods. The new model combines existing models, including detailed radiative and hydrodynamic models that assess built-tree interactions, and includes new parameterizations for impacts of tree foliage distribution. BEP-Tree is evaluated against unique datasets from three cities enabling assessment of modelled radiation, energy exchanges and road and air temperatures across the diurnal cycle. Urban trees redirect sensible heat into latent heat and reduce pedestrian-level solar radiation, wind, and temperatures during daytime. Thermal climate and energy exchanges are more sensitive to street tree density than height. Coupled with a mesoscale model, BEP-Tree enables assessment of urban forest-induced neighbourhood-to-city scale climate impacts during fair weather periods.
•Urban trees differ from shorter vegetation because they provide shade and shelter.•A multi-layer urban canopy model that assesses built-tree interactions is developed.•The new model represents climate impacts of trees at pedestrian-level across cities.•The new model is evaluated at two scales using novel datasets from three cities.•Urban trees impact local climate via multiple interacting physical mechanisms.
This paper presents an economically viable, sensitivity-optimized fluorescence sensor for detecting low concentrations of fluorophores in the visible spectrum range. The sensor employs a deep ...ultraviolet (DUV) 275-nm LED and a dichroic mirror to establish a co-axial optical path for excitation and emission. Instead of utilizing a general-purposed spectrometer optimized for high spectral resolution, the sensor strikes a balance between resolution and sensitivity by using an appropriate aperture size and optimized optical design tailored for the spectral characteristics of fluorophores. The manuscript demonstrates measurements of ppb-level rare earth element (REE) samples containing terbium (Tb), europium (Eu), dysprosium (Dy), and samarium (Sm) in aqueous solutions. Through balanced design that optimizes collection of fluorescence emission without losing spectral information, this work shows the feasibility of developing a low-cost, compact, and highly sensitive fluorescence sensors with improved detection sensitivity when compared to bench-top commercial spectrofluorometers at far higher costs.
The Nab experiment will measure the correlation a between the momenta of the beta particle and antineutrino in neutron decay as well as the Fierz term b which distorts the beta spectrum.
Rare earth elements (REEs) are critical to numerous technologies; however, a combination of increasing demand, environmental concerns, and monopolistic marketplace conditions has spurred interest in ...boosting the domestic REE production from sources such as coal utilization byproducts. The economic viability of this approach requires rapid, inexpensive, and sensitive analytical techniques capable of characterizing the REE content during resource exploration and downstream REE processing (e.g., analyzing REE separation, concentration, and purification production steps). Luminescence-based sensors are attractive because many REEs may be sensitized to produce element-specific emission. Hence, a single material may simultaneously detect and distinguish multiple REEs. Metal–organic frameworks (MOFs) can sensitize multiple REEs, but their viability has been hindered by sensitivity and selectivity challenges. Understanding how the MOF structure impacts the REE sensing efficacy is critical to the rational design of new sensors. Here, we evaluate the sensing performance of seven different anionic zinc-adeninate MOFs with different organic linkers and/or structures for the visible-emitting REEs Tb, Dy, Sm, and Eu. The choice of a linker determines which REEs are sensitized and significantly influences their sensitivity and selectivity against competing species (here, Fe(II) and HCl). For a given linker, structural changes to the MOF can further fine-tune the performance. The MOFs produce some of the lowest detection limits (sub-10 ppb for Tb) reported for the aqueous sensitization-based REE detection. Importantly, the most selective MOFs demonstrated the ability to sensitize the REE signal at sub-ppm levels in a REE-spiked acid mine drainage matrix, highlighting their potential for use in real-world sensing applications.
Abstract
Fibrolamellar carcinoma (FLC) is an often-lethal liver malignancy of adolescents and young adults. No systemic therapies are currently approved for FLC, so novel treatments are needed to ...improve patient outcomes. A promising therapeutic vulnerability in FLC is a highly-conserved gene fusion between DNAJB1 and PRKACA. The resultant fusion protein is identical in more than 90% of patients, making it a potentially ideal neoantigen target for T cell-based immunotherapy. The goal of our study was to test if DNAJB1-PRKACA neoantigens could elicit T cell responses and serve as targets for immunotherapy. Spatial transcriptomic analyses of FLC tumor tissue indicated that CD8 T cells could infiltrate FLC tumors, but expressed exhaustion markers such as TOX. Nevertheless, we expanded T cells from an FLC patient tumor ex vivo and detected T cells that produced IFNγ and TNFα in response to stimulation with a fusion neoantigen. We then used functional response after peptide stimulation or peptide-MHC tetramer staining to identify fusion-specific T cell receptors (TCRs) in both FLC patients and healthy donors. We expressed these TCRs in primary human T cells and found that cells expressing fusion-specific TCRs bound to their cognate tetramer and produced IFNγ, TNFα, and IL-2 in response to stimulation with their cognate peptide. TCR-expressing cells also specifically killed target cells presenting their cognate fusion peptide in vitro. Ongoing experiments will test if cells expressing these TCRs can control growth of fusion-expressing tumors in vivo. Together, these studies have defined the first reported fusion-specific T cell response in an FLC patient, as well as fusion-specific TCRs that hold promise for development in adoptive T cell therapies.
Supported by grants from NIH (R01 AI136514, F31 CA254423) and The Mark Foundation for Cancer Research (Aspire Award)
Abstract
Fibrolamellar carcinoma (FLC) is a rare liver tumor with poor outcomes and for which novel therapies are urgently needed. A potential therapeutic vulnerability in FLC is a gene fusion ...between DNAJB1 and PRKACA that is expressed in all FLC tumors and has been shown to drive FLC tumorigenesis. Genetic mutations that alter amino acid sequence, including gene fusions, can be presented as neoantigens by MHC class I molecules on tumor cells and thereby elicit anti-tumor CD8 T cell responses. We hypothesize that DNAJB1-PRKACA fusion neoantigens can elicit T cell responses in FLC patients and serve as targets for T cell-based immunotherapies for FLC. To test this hypothesis, T cells isolated and expanded from an FLC patient tumor were stimulated with DNAJB1-PRKACA fusion peptides, which reproducibly induced cytokine production measured by intracellular cytokine staining. Single cell gene expression and T cell receptor (TCR) repertoire analysis of patient tumors using the 10X Genomics platform identified clonally expanded TCR clonotypes that were associated with expression of cytokines and activation markers in response to fusion peptide stimulation. These TCRs were cloned and expressed in Jurkat 76 cells to test their fusion specificity and their ability to mediate in vitro functional responses to fusion neoantigens. When stimulated with their cognate fusion neoepitope, TCR-expressing cells produced cytokines, expressed the early activation marker CD69, and downregulated surface expression of TCR and CD3. These studies have therefore identified T cell responses against the DNAJB1-PRKACA fusion for the first time, as well as identified DNAJB1-PRKACA-specific TCR clonotypes that could be used to develop novel immunotherapies for FLC.
We report the first observation of the parity-violating gamma-ray asymmetry A_{γ}^{np} in neutron-proton capture using polarized cold neutrons incident on a liquid parahydrogen target at the ...Spallation Neutron Source at Oak Ridge National Laboratory. A_{γ}^{np} isolates the ΔI=1, ^{3}S_{1}→^{3}P_{1} component of the weak nucleon-nucleon interaction, which is dominated by pion exchange and can be directly related to a single coupling constant in either the DDH meson exchange model or pionless effective field theory. We measured A_{γ}^{np}=-3.0±1.4(stat)±0.2(syst)×10^{-8}, which implies a DDH weak πNN coupling of h_{π}^{1}=2.6±1.2(stat)±0.2(syst)×10^{-7} and a pionless EFT constant of C^{^{3}S_{1}→^{3}P_{1}}/C_{0}=-7.4±3.5(stat)±0.5(syst)×10^{-11} MeV^{-1}. We describe the experiment, data analysis, systematic uncertainties, and implications of the result.
Cobalt is critical to energy-relevant technologies, and demand for cobalt will increase significantly with growing global adoption of renewables. However, supply chain stability is threatened by ...economic and geopolitical factors, incentivizing domestic cobalt production from alternative resources such as coal, coal utilization byproducts (e.g., ash, acid mine drainage) and electronic waste. Rapid, inexpensive, and portable characterization techniques are needed to reduce production costs associated with cobalt prospecting and process monitoring. Here, in this research, we develop a compact, portable fiber optic luminescent probe for cobalt using phosphorus and nitrogen co-doped carbon dots as the sensing material. The carbon dot emission overlaps well with the cobalt absorption band at ~510 nm, leading to a selective decrease in emission as a function of cobalt concentration. The system responds nearly instantly to the presence of cobalt, with detection limits of 0.7 and 3.5 ppm in water and pH 1.68 buffer, respectively, providing comparable performance to a commercial spectrometer at a significantly lower cost. Moreover, the sensor is selective for cobalt in the presence of 13 of the most common metal ions encountered in coal utilization byproducts and is responsive to cobalt when spiked into an acid mine drainage leachate sample, highlighting the sensor's potential for real-world deployment in challenging matrices. In addition, integrating the carbon dots with a filter paper substrate produced ‘test strip’ sensors that exhibited a selective and sensitive visual response to cobalt using a handheld UV lamp. Taken together, the sensing system represents a significant step forward in the development of low-cost practical sensors for high-value metals in complex streams.
Quantum computing and simulations are creating transformative opportunities by exploiting the principles of quantum mechanics in new ways to generate and process information. It is expected that a ...variety of areas ranging from day-to-day activities to making advanced scientific discoveries are going to benefit from such computations. Several early stage applications of quantum computing and simulation have already been demonstrated, and these preliminary results show that quantum computing and simulations could significantly accelerate the deployment of new technologies urgently needed to meet the growing demand for energy while safeguarding the environment. Exciting examples include developing new materials such as alloys, catalysts, oxygen carriers, CO2 sorbents/solvents, and energy storage materials; optimizing traffic flows and energy supply chains; locating energy generation facilities such as wind and solar farms and fossil and nuclear power plants; designing pipeline networks for transporting hydrogen, natural gas, and CO2; and speeding up tasks such as seismic imaging and inversion, reservoir simulation, and computational fluid dynamics. In this review, we introduce different aspects of quantum computing and simulations and discuss the status of theoretical and experimental approaches. We then specifically highlight a growing number of application areas in the energy sector. We conclude by providing an analysis of high-value application directions to address energy sector challenges.
Here, we use solution and solid-state
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P NMR to study the ligand environment of water soluble, phosphine-terminated gold nanoparticles. The resulting spectra indicate that particle-bound phosphine ...ligands occupy an unexpectedly monodisperse ligand environment. This uniformity then facilitates one of the first descriptions of distinct
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Au coupling in colloidal nanoparticles.
Phosphine-terminated gold nanoparticles exhibit unexpectedly uniform ligand environments that enable the identification of
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Au coupling for the first time in these systems.
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