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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records

Implications of stop-and-go traffic on training learning-based car-following control

Learning-based car-following control (LCC) of connected and autonomous vehicles (CAVs) is gaining significant attention with the advancement of computing power and data accessibility. While the flexibility and large model capacity of model-free architecture enable LCC to potentially outperform the model-based car-following (CF) model in improving traffic efficiency and mitigating congestion, the generalizability of LCC for traffic conditions different from the training environment/dataset is not well-understood. Herein, this study seeks to explore the impact of stop-and-go traffic in the training dataset on the generalizability of LCC. It uses the characteristics of lead vehicle trajectories to describe stop-and-go traffic, and links the theory of identifiability (i.e., obtaining a unique parameter estimation result using sensor measurements) to the generalizability of behavior cloning (BC) and policy-based deep reinforcement learning (DRL). Correspondingly, the study shows theoretically that: (i) stop-and-go traffic can enable the property of identifiability and enhance the control performance of BC-based LCC in different traffic conditions; (ii) stop-and-go traffic is not necessary for DRL-based LCC to generalize to different traffic conditions; (iii) DRL-based LCC trained with only constant-speed lead vehicle trajectories (not sufficient to ensure identifiability) can be generalized to different traffic conditions; and (iv) stop-and-go traffic increases variance in the training dataset, which improves the convergence of parameter estimation while negatively impacting the convergence of DRL to the optimal control policy. Numerical experiments validate the above findings, illustrating that BC-based LCC entails comprehensive training datasets for generalizing to different traffic conditions, while DRL-based LCC can achieve generalization with simple free-flow traffic training environments. This further suggests DRL as a more promising and cost-effective LCC approach to reduce operational costs, mitigate traffic congestion, and enhance safety and mobility, which can accelerate the deployment and acceptance of CAVs.

33 ADVANCED PROPULSION SYSTEMS↗

Disruption of adenosine 2A receptor improves the anti-tumor function of anti-mesothelin CAR T cells both in vitro and in vivo

Chimeric antigen receptor (CAR) T cells have been successfully used for the treatment of hematological malignancies including acute and chronic lymphoblastic leukemia. However, results of CAR T cell projects in solid tumors have been less impressive to date, partly because of immunosuppressive tumor microenvironment (TME). It is widely known that high adenosine production is an important factor causing tumor-induced immunosuppression in TME, and adenosine mediates the suppression of anti-tumor T cell responses via binding and signaling through adenosine 2a receptor (A2aR). Previous studies have shown that adenosine generated by cancer cells significantly inhibits T cell anti-tumor activity through binding and then activating adenosine 2A receptors (A2aRs) of T cells. Based on the previous work, in our study, we evaluated whether A2aR disruption by shRNA could enhance the anti-tumor function of anti-mesothelin (MSLN) CAR T cells both in vitro and in vivo. For this goal above, we used MSLN-positive human ovarian serous carcinoma cells (SKOV3) and human colon cancer cells (HCT116) as target cancer cells while MSLN-negative human ovarian cancer cells (ES2) as non-target cancer cells. We observed that targeting cell-intrinsic A2aR through shRNA overexpression caused significant A2aR disruption in CAR T cells and profoundly increased CAR T cell efficacy in both CAR T cell cytokine production and cytotoxicity towards MSLN-positive cancer cells in vitro. More importantly, in SKOV3 xenograft mouse models, anti-MSLN CAR-T cells significantly reduced the tumor burden compared with non-transduced T cells, and the anti-tumor activity of A2aR-disrupted anti-MSLN CAR-T cells was stronger than that of wild-type anti-MSLN CAR-T cells. Altogether, our study showed enhanced anti-tumor efficacy caused by shRNA-mediated A2aR disruption in anti-MSLN CAR T cells both in vitro and in vivo, which proved that shRNA-mediated modification of gene expression might be an excellent strategy for improving CAR T cell function in immunosuppressive tumor microenvironment (TME) and could potentially improve the outcome of treatment in clinical trials.

60 APPLIED LIFE SCIENCES↗

How do perceptions of safety and car ownership importance affect autonomous vehicle adoption?

In this study, we explicitly modeled how individuals' perceptions of automated vehicle (AV) safety and the importance they place on car ownership affect mode choices involving conventional and automated vehicles in the context of privately owned cars and ridehailing services. We adopted psychometric questions to capture these two latent variables and designed a stated preference survey based on the participants' actual travel patterns. Then, we quantified the impact of these latent variables on mode choices using an integrated choice and latent variable (ICLV) model. We found that both latent variables have a statistically significant effect on mode choices. The results show that car ownership importance has the most potent effect on privately owned cars (conventional car and self-driving car), followed by driverless ridehailing and conventional ridehailing. We also found that changes in safety perception are equivalent to sizable changes in price. In addition, we further investigated the impact of improvements in safety perception through four scenarios. The scenario testing results show that as the distribution of perceived safety is compressed toward positive safety perception, the market share of AVs spikes and dominates regular cars. Our results demonstrate that based on our respondents' current understanding of AVs, even if AV prices were comparable to regular cars, we cannot expect widespread use of AVs. However, improvements in AVs' safety and, consequently, consumer safety perception can considerably expand AVs' market share, and may offset the high cost of using the technology.

33 ADVANCED PROPULSION SYSTEMS↗

Gas detection sensitivity of hybrid fs/ps and fs/ns CARS

Coherent anti-Stokes Raman scattering (CARS) is commonly used for thermometry and concentration measurement of major species. The quadratic scaling of CARS signal with number density has limited the use of CARS for detection of minor species, where more sensitive approaches may be more attractive. However, significant advancements in ultrafast CARS approaches have been made over the past two decades, including the development of hybrid CARS demonstrated to yield greatly increased excitation efficiencies. Yet, detailed detection limits of hybrid CARS have not been well established. In this Letter, detection limits for N 2 , H 2 , CO, and C 2 H 4 by point-wise hybrid femtosecond (fs)/picosecond (ps) CARS are determined to be of the order of 10 15 molecules/cm 3 . Here, the possible benefit of fs/nanosecond (ns) hybrid CARS is also discussed.

74 ATOMIC AND MOLECULAR PHYSICS↗

How Time Inefficient and Uncertain are Paratransit Trips Compared to Car Trips

The Americans with Disabilities Act (ADA) stipulates that paratransit mobility be comparable to public transit. However, with just under 5% of the population relying on public transportation, transit is not a representative benchmark. To highlight this inequality, we compare trip times by paratransit to counterfactual car-based travel. Using 2.5 years of demand data from the Denver Regional Transportation District's Access-a-Ride service, we compare paratransit trip times to counterfactual car-based trips for the same origin-destination pairs, controlling for various trip characteristics. Compared to car travel, the findings indicate high variability and uncertainty associated with paratransit trip times. For the same origin-destination pairs, the mean paratransit trip time is almost twice that of the mean car travel time, with a standard deviation for paratransit trip time fourfold that of the standard deviation for car trip time. For perspective, traveling an average of 10 mi during the 7-8 a.m. morning peak can take about 16 min by car with almost no variability, while that same trip can take an average of 25 min by paratransit, with 5% of trips being outside the 95% confidence interval and thus unpredictable. Paratransit trip time inefficiency tends to be particularly worse for females; older adults; those making trips between 9 and 11 a.m.; cash-paying customers; those making shorter trips; and those traveling during inclement weather, including cold temperatures. These findings suggest a need to re-assess using public transit as a benchmark for paratransit supply as regulated by the ADA.

accessible transportation and mobility↗

Activation of the CaR-CSE/H2S pathway confers cardioprotection against ischemia-reperfusion injury

Ischemia-reperfusion (I/R) injury is a multifactorial process triggered when an organ is subjected to transiently reduced blood supply. The result is a cascade of pathological complications and organ damage due to the production of reactive oxygen species following reperfusion. The present study aims to evaluate the role of activated calcium-sensing receptor (CaR)-cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway in I/R injury. Firstly, an I/R rat model with CSE knockout was constructed. Transthoracic echocardiography, TTC and HE staining were performed to determine the cardiac function of rats following I/R Injury, followed by TUNEL staining observation on apoptosis. Besides, with the attempt to better elucidate how CaR-CSE/H2S affects I/R, in-vitro culture of human coronary artery endothelial cells (HCAECs) was conducted with gadolinium chloride (GdCl3, a CaR agonist), H{sub 2}O{sub 2}, siRNA against CSE (siCSE), or W7 (a CaM inhibitor). The interaction between CSE and CaM was subsequently detected. Plasma oxidative stress indexes, H2S and CSE, and apoptosis-related proteins were all analyzed following cell apoptosis. We found that H2S elevation led to the improvement whereas CSE knockdown decreased cardiac function in rats with I/R injury. Moreover, oxidative stress injury in I/R rats with CSE knockout was aggravated, while the increased expression of H2S and CSE in the aortic tissues resulted in alleviated the oxidative stress injury. Moreover, increased H2S and CSE levels were found to inhibit cell apoptotic ability in the aortic tissues after I/R injury, thus attenuating oxidative stress injury, accompanied by inhibited expression of apoptosis-related proteins. In HCAECs following oxidative stress treatment, siCSE and CaM inhibitor were observed to reverse the protection of CaR agonist. Coimmunoprecipitation assay revealed the interaction between CSE and CaM. Taken together, all above-mentioned data provides evidence that activation of the CaR-CSE/H2S pathway may confer a potent protective effect in cardiac I/R injury.

60 APPLIED LIFE SCIENCES↗

Molecular basis of crosstalk in nuclear receptors: heterodimerization between PXR and CAR and the implication in gene regulation

The 48 human nuclear receptors (NRs) form a superfamily of transcription factors that regulate major physiological and pathological processes. Emerging evidence suggests that NR crosstalk can fundamentally change our understanding of NR biology, but detailed molecular mechanisms of crosstalk are lacking. Here, we report the molecular basis of crosstalk between the pregnane X receptor (PXR) and constitutive androstane receptor (CAR), where they form a novel heterodimer, resulting in their mutual inhibition. PXR and CAR regulate drug metabolism and energy metabolism. Although they have been broadly perceived as functionally redundant, a growing number of reports suggests a mutual inhibitory relation, but their precise mode of coordinated action remains unknown. Using methods including RNA sequencing, small-angle X-ray scattering and crosslinking mass spectrometry we demonstrate that the mutual inhibition altered gene expression globally and is attributed to the novel PXR–CAR heterodimerization via the same interface used by each receptor to heterodimerize with its functional partner, retinoid X receptor (RXR). These findings establish an unexpected functional relation between PXR, CAR and RXR, change the perceived functional relation between PXR and CAR, open new perspectives on elucidating their role and designing approaches to regulate them, and highlight the importance to comprehensively investigate nuclear receptor crosstalk.

59 BASIC BIOLOGICAL SCIENCES↗

Omar Ishak: Bioengineer by day, sports car tinkerer by night

Omar Ishak was 13 when he got his first car — or rather, the pieces of his first car. He had helped in his dad’s auto shop in the summers from age 10 to 12, but the vehicle that his dad presented, an Acura Integra, was a challenging first car. Missing most of one side and without a working engine, it seemed to Omar as if it were better off as scrap metal. "If you can piece together all the parts," Omar remembers his dad saying, "you can have it." Omar, now a technical project manager in Weapons Production (ALDWP) with the Transition to Operations/Readiness (PPI-3) group, at first felt overwhelmed at the enormity of what needed to be finished. As a child, he’d played with Legos and liked to tinker and take broken things apart. Then he’d become fascinated with building smaller-scaled model cars and, by the time his dad owned that shop, the fascination had manifested into real cars.

99 GENERAL AND MISCELLANEOUS↗

CO 2 chirped-probe-pulse femtosecond CARS thermometry

The application of CO 2 chirped-probe-pulse (CPP) fs coherent anti-Stokes Raman scattering (CARS) for flame thermometry is discussed. A phenomenological model for CO 2 /O 2 CPP fs CARS was developed, and the simulations showed the potential for CO 2 temperature measurements free of interferences from O 2 and with no contribution from the nonresonant background by using a long-time delay for the chirped probe pulse. The accuracy and precision for CO 2 CPP fs CARS thermometry is compared with N 2 CPP fs CARS thermometry for temperatures between 295 K and 1420 K. The measurement accuracy for the CO 2 measurements is comparable with that for the N 2 measurements, while the precision for the CO 2 temperature measurements is significantly better at lower temperatures. In conclusion, we also demonstrate that accurate flame thermometry using a single set of laser parameters can be achieved using the delayed CPP approach.

42 ENGINEERING↗

Spectral Narrowing Accompanies Enhanced Spatial Resolution in Saturated Coherent Anti-Stokes Raman Scattering (CARS): Comparisons of Experiment and Theory

Here, we demonstrate theoretically and confirm experimentally the mechanism by which spectral narrowing accompanies enhanced spatial resolution in a saturated coherent anti-Stokes Raman scattering (CARS) signal that is demodulated at the third harmonic (3$f$) of the pump modulation frequency ($f$). Under these modulation conditions, theory predicts a narrowing of the full-width at half-maximum (FWHM) of the CARS spectrum by a factor of 2.0 with respect to that of the spectrum obtained by demodulation at the fundamental frequency. Theory also predicts an improvement of spatial resolution by a factor of 1.7. Experimentally, narrowing of the FWHM of the CARS spectrum of 1,4-bis((E)-2-methylstyryl) benzene (MSB) crystals by a factor of 2.5 is observed upon saturation. Further experimental confirmation is provided from investigating diamond particles, for which spectral narrowing was enhanced by a factor of 2.8 and spatial resolution was enhanced by a factor of 2. Details of the mechanism and execution of the saturated CARS experiment are elucidated and limits to its applicability are suggested, one of which is the conclusion that the saturation approach is not suitable for extraction of harmonics beyond 3$f$ . In this work we have developed a more comprehensive understanding of the correlation between the observed experimental results and experimental factors than has been previously reported.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Cross-HLA targeting of intracellular oncoproteins with peptide-centric CARs

The majority of oncogenic drivers are intracellular proteins, thus constraining their immunotherapeutic targeting to mutated peptides (neoantigens) presented by individual human leukocyte antigen (HLA) allotypes. However, most cancers have a modest mutational burden that is insufficient to generate responses using neoantigen-based therapies. Neuroblastoma is a paediatric cancer that harbours few mutations and is instead driven by epigenetically deregulated transcriptional networks. Here we show that the neuroblastoma immunopeptidome is enriched with peptides derived from proteins that are essential for tumourigenesis and focus on targeting the unmutated peptide QYNPIRTTF, discovered on HLA-A*24:02, which is derived from the neuroblastoma dependency gene and master transcriptional regulator PHOX2B. To target QYNPIRTTF, we developed peptide-centric chimeric antigen receptors (CARs) using a counter-panning strategy with predicted potentially cross-reactive peptides. We further hypothesized that peptide-centric CARs could recognize peptides on additional HLA allotypes when presented in a similar manner. Informed by computational modelling, we showed that PHOX2B peptide-centric CARs also recognize QYNPIRTTF presented by HLA-A*23:01 and the highly divergent HLA-B*14:02. Finally, we demonstrated potent and specific killing of neuroblastoma cells expressing these HLAs in vitro and complete tumour regression in mice. These data suggest that peptide-centric CARs have the potential to vastly expand the pool of immunotherapeutic targets to include non-immunogenic intracellular oncoproteins and widen the population of patients who would benefit from such therapy by breaking conventional HLA restriction.

59 BASIC BIOLOGICAL SCIENCES↗

Targeting of intracellular oncoproteins with peptide-centric CARs

The majority of oncogenic drivers are intracellular proteins, constraining their immunotherapeutic targeting to mutated peptides (neoantigens) presented by individual human leukocyte antigen (HLA) allotypes. However, most cancers have a modest mutational burden that is insufficient for generating responses using neoantigen-based therapies. Neuroblastoma is a paediatric cancer that harbours few mutations and is instead driven by epigenetically deregulated transcriptional networks. Here we show that the neuroblastoma immunopeptidome is enriched with peptides derived from proteins essential for tumorigenesis. We focused on targeting the unmutated peptide QYNPIRTTF discovered on HLA-A*24:02, which is derived from the neuroblastoma-dependency gene and master transcriptional regulator PHOX2B. To target QYNPIRTTF, we developed peptide-centric chimeric antigen receptors (PC-CARs) through a counter panning strategy using predicted potentially cross-reactive peptides. We further proposed that PC-CARs can recognize peptides on additional HLA allotypes when presenting a similar overall molecular surface. Informed by our computational modelling results, we show that PHOX2B PC-CARs also recognize QYNPIRTTF presented by HLA-A*23:01, the most common non-A2 allele in people with African ancestry. Finally, we demonstrate potent and specific killing of neuroblastoma cells expressing these HLAs in vitro and complete tumour regression in mice. These data suggest that PC-CARs have the potential to expand the pool of immunotherapeutic targets to include non-immunogenic intracellular oncoproteins and allow targeting through additional HLA allotypes in a clinical setting.

60 APPLIED LIFE SCIENCES↗

Resolved rotation–vibration non-equilibrium with rotational VIPA-CARS

Simultaneous rotational and vibrational temperatures are measured in an N 2 plasma with rotational coherent anti-Stokes Raman scattering (CARS) resolved with a virtually imaged phased array (VIPA)-based spectrometer. A VIPA spectrally separates rotational transitions for each vibrational state, allowing vibrational populations to be directly measured. VIPA-CARS is shown to provide more accurate measurements of non-equilibrium temperatures than grating-resolved rotational CARS. The general characteristics, limitations, and potential uses of VIPA-CARS are discussed.

Steinmetz, S. A. (ORCID:0000000311014662)↗

CAR-T Cell Therapy: Mechanism, Management, and Mitigation of Inflammatory Toxicities

Engineered T cell therapies such as chimeric antigen receptor (CAR) expressing T cells (CAR-T cells) have great potential to treat many human diseases; however, inflammatory toxicities associated with these therapies present safety risks and can greatly limit its widespread use. This article briefly reviews our current understanding of mechanisms for inflammatory toxicities during CAR T-cell therapy, current strategies for management and mitigation of these risks and highlights key areas of knowledge gap for future research..

59 BASIC BIOLOGICAL SCIENCES↗

Post-detonation fireball thermometry via femtosecond-picosecond coherent anti-Stokes Raman Scattering (CARS)

Accurate knowledge of post-detonation fireball temperatures is important for understanding device performance and for validation of numerical models. Such measurements are difficult to make even under controlled laboratory conditions. Here, temperature measurements were performed in the fireball of a commercial detonator (RP-80, Teledyne RISI). The explosion and fragments were contained in a plastic enclosure with glass windows for optical access. A hybrid femtosecond-picosecond (fs-ps) rotational coherent anti-Stokes Raman scattering (CARS) instrument was used to perform gas-phase thermometry along a one-dimensional measurement volume in a single laser shot. The 13-mm-thick windows on the explosive-containment housing introduced significant nonlinear chirp on the fs lasers pulses, which reduced the Raman excitation bandwidth and did not allow for efficient excitation of high-J Raman transitions populated at flame temperatures. To overcome this, distinct pump and Stokes pulses were used in conjunction with spectral focusing, achieved by varying the relative timing between the pump and Stokes pulses to preferentially excite Raman transitions relevant to flame thermometry. Light scattering from particulate matter and solid fragments was a significant challenge and was mitigated using a new polarization scheme to isolate the CARS signal. Fireball temperatures were measured 35–40 mm above the detonator, 12–25 mm radially outward from the detonator centerline, and at 18 and 28 µs after initiation. At these locations and times, significant mixing between the detonation products and ambient air had occurred thus increasing the nitrogen-based CARS thermometry signal. Initial measurements show a distribution of fireball temperatures in the range 300–2000 K with higher temperatures occurring 28 µs after detonation.

42 ENGINEERING↗

The Close AGN Reference Survey (CARS)

Active galactic nuclei (AGN) are thought to be responsible for the suppression of star formation in massive ~10 10 M ⊙ galaxies. While this process is a key feature in numerical simulations of galaxy formation, it has not been unambiguously confirmed in observational studies yet. The characterization of the star formation rate (SFR) in AGN host galaxies is challenging as AGN light contaminates most SFR tracers. Furthermore, the various SFR tracers are sensitive to different timescales of star formation from approximately a few to 100 Myr. We aim to obtain and compare SFR estimates from different tracers for AGN host galaxies in the Close AGN Reference Survey (CARS) to provide new observational insights into the recent SFR history of those systems. We constructed integrated panchromatic spectral energy distributions to measure the far infrared (FIR) luminosity as a tracer for the recent (< 100 Myr) SFR. In addition we used the integral-field unit observation of the CARS targets to employ the Hα luminosity decontaminated by AGN excitation as a proxy for the current (< 5 Myr) SFR. We find that significant differences in specific SFR of the AGN host galaxies as compared with the larger galaxy population disappear once cold gas mass, in addition to stellar mass, is used to predict the SFR for a specific AGN host. Only a tentative trend with the inclination of the host galaxy remains, such that SFR appears slightly lower than expected when the galaxies of unobscured AGN appear more edge-on along our line-of-sight, particular for dust-insensitive FIR-based SFRs. We identify individual galaxies with a significant difference in their SFR which can be related to a recent enhancement or decline in their SFR history that might be related to various processes including interactions, gas consumption, outflows, and AGN feedback. AGN can be present in various stages of galaxy evolution which makes it difficult to relate the SFR solely to the impact of the AGN. Our study shows that stellar mass alone is an insufficient parameter to estimate the expected SFR of an AGN host galaxy compared to the underlying non-AGN galaxy population. We do not find any strong evidence for a global positive or negative AGN feedback in the CARS sample. However, there is tentative evidence that (1) the relative orientation of the AGN engine with respect to the host galaxies might alter the efficiency of AGN feedback and that (2) the recent SFH is an additional tool to identify rapid changes in galaxy growth driven by the AGN or other processes.

79 ASTRONOMY AND ASTROPHYSICS↗

Numerical study of pure rotational fs/ps CARS coherence beating at high pressure and for multi-species rotation-vibration non-equilibrium thermometry

Coherent anti-Stokes Raman scattering (CARS) has long been the gold standard for non-intrusively measuring gas temperature in reacting flows such as flames and plasmas. Recently, the development of ultrafast hybrid fs/ps CARS has enabled the exploitation of coherence beating between neighboring spectral lines to simultaneously measure rotational and vibrational temperatures from a single pure rotational spectrum. However, the influence of non-Boltzmann vibrational state distributions and limitations due to collisional dephasing at pressures greater than 1 atm remains unclear. In this work, we use spectral simulations to investigate the effects of non-Boltzmann vibrational state distributions and the applicability of coherence beating at pressures up to 10 atm. We show that short probe pulses can be leveraged to quantify non-Boltzmann vibrational state distributions of N2. Furthermore, we demonstrate that fs/ps CARS coherence beating can simultaneously provide sensitive measurements of rotational and vibrational temperatures of both O2 and N2 in air. A sensitivity analysis was conducted to qualitatively explain the accuracy and precision comparisons between probe delays.

Chen, Timothy Y. (ORCID:0000000330269767)↗

Coherent anti-Stokes Raman scattering with squeezed light: CARS for quantum-enhanced spectroscopy and imaging

We theoretically investigate quantum-enhanced coherent anti-Stokes Raman scattering (CARS) using squeezed light to amplify vibrational transition rates at low photon flux. Quantum sensing approaches are needed for nondestructive nanometrology such as in bioimaging where reduced photodamage is desired while retaining resolution and sensitivity. We analyze both single-mode squeezing applied to the pump field and two-mode squeezing between the pump and Stokes fields. We also show that the ordering of displacement and squeezing operations—whether displacement precedes squeezing or squeezing precedes displacement—has an impact on the resulting CARS transition amplitudes due to a difference in the photon number and the quantum-enhancement coefficients, with the latter offering a stronger enhancement in the case of two modes squeezing of the pump and Stokes under experimentally accessible conditions. Furthermore, our calculations capture these quantum enhancements through the intrinsic photon-number correlations of squeezed light, eliminating the need for interferometric detection or higher pump powers that are otherwise required to reach comparable sensitivities in classical CARS. Finally, we outline a quantum plasmonic extension of our model in which local field enhancements caused by surface plasmon excitation in metallic nanoparticles can be incorporated via mode-selective field amplification factors, offering a pathway toward combining squeezed-light quantum optics with surface-enhanced nanoscale spectroscopy and imaging.

Atomic & molecular structure↗