517 research outputs found
Efficient picosecond x-ray pulse generation from plasmas in the radiation dominated regime
The efficient conversion of optical laser light into bright ultrafast x-ray pulses in laser created plasmas is of high interest for dense plasma physics studies, material science, and other fields. However, the rapid hydrodynamic expansion that cools hot plasmas has limited the x-ray conversion efficiency (CE) to 1% or less. Here we demonstrate more than one order of magnitude increase in picosecond x-ray CE by tailoring near solid density plasmas to achieve a large radiative to hydrodynamic energy loss rate ratio, leading into a radiation loss dominated plasma regime. A record 20% CE into ℎ>1 keVhν>1 keV photons was measured in arrays of large aspect ratio Au nanowires heated to keV temperatures with ultrahigh contrast femtosecond laser pulses of relativistic intensity. The potential of these bright ultrafast x-ray point sources for table-top imaging is illustrated with single shot flash radiographs obtained using low laser pulse energy. These results will enable the deployment of brighter laser driven x-ray sources at both compact and large laser facilities.Fil: Hollinger, Reed. Department Of Electrical And Engineering;Fil: Bargsten, Clayton. Department Of Electrical And Engineering;Fil: Shlyaptsev, Vyacheslav N.. Department Of Electrical And Engineering;Fil: Kaymak, Vural. Institut Fur Theoretische Physik, Heinrich-heine-univer;Fil: Pukhov, Alexander. Heinrich-heine-universität Düsseldorf;Fil: Capeluto, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; ArgentinaFil: Wang, Shoujun. Department Of Electrical And Engineering;Fil: Rockwood, Alex. Department Of Electrical And Engineering;Fil: Wang, Yong. Department Of Electrical And Engineering;Fil: Townsend, Amanda. Department Of Electrical And Engineering;Fil: Prieto, Amy. Department Of Electrical And Engineering;Fil: Stockton, Patrick. Department Of Electrical And Engineering;Fil: Curtis, Alden. Department Of Electrical And Engineering;Fil: Rocca, Jorge J.. Department Of Electrical And Engineering
An investigation into catalysts to improve the low temperature performance of an SCR
Selective catalytic reduction with NH3 is considered as one of the most effective technologies controlling NOx emission. Metal Fe based catalysts were used in the investigation to improve the low temperature performance of NOx conversion. The temperature range studied was between 150 degrees C and 350 degrees C with the interval of 50 degrees C. The honeycomb catalysts were prepared by an impregnation method. The study also included characterization of catalysts by BET, XRD, H2-TPR, SEM and XPS methods. It is found an increase in metal Fe content from 2 to 6 % wt. offers an improvement in the catalytic performance. However, a further increment in Fe content will result in a decrease in its performance. More than 90 % NOx conversion rate could be achieved over the Fe-based honeycomb catalyst at a low temperature by doping with Ni and Zr metal with different weights. Among all the catalysts studied, the mixed metal catalyst of Fe-Ni-Zr is found the most potential one, not only because of its higher NOx conversion rate at a low temperature, but also because of its wider operation temperature window. The effect of gas hourly space velocity (GHSV) was also investigated in the study and results show as GHSV increases that reduction of NOx is decreased
Selective growth of monolayer semiconductors for diverse synaptic junctions
The information computation through synapse networks in the brain plays a vital role for cognitive behaviors such as image/video recognition, self-learning, and decision-making. Achieving proper synaptic networks by conventional semiconductor and memristive devices has encountered critical issues such as the spatial density requiring a number of transistors for one synapse, reliable filament formation in memristors, or emulating diverse excitatory and inhibitory synaptic plasticity with two-terminal device geometry. Here, we report selective growth of variously doped MoS2 with controllable conductance plasticity, which can be used for emulating diverse synaptic junctions. The conductance plasticity in the monolayer MoS2 was found to originate from resistive-heating near the junctions with electrodes in the two-terminal device geometry and the carrier concentration-dependent metal-insulator transition in the MoS2 channel. A spatiotemporal synaptic summation is demonstrated where the firing of a proper postsynaptic membrane potential can be designed for cognitive processes. Compared with previously reported three terminal synaptic devices with atomically thin materials, our two-terminal devices with flexible synaptic strengths have advantages for integrating three-dimensional neuronal networks. This provides a new insight on two-dimensional materials as a promising arena for integrated synaptic functionalities in artificial neural networks.
Direct Quantitative Detection of Microrna with a Purification-Free, Amplification-Free and Label-Free Technique
MicroRNAs play key roles in various types of cellular processes such as cell proliferation, and differentiation via post-transcriptional regulation. Therefore, they have great potential of being promising biomarkers for disease diagnosis and as a result have attracted much attention. To address the increasing need for their precise detection, many quantitative approaches have been developed. Recently, a new direct detection technique, Exchange-Induced Remnant Magnetization Spectroscopy (ExIRMS) has been reported by our laboratory with no amplification or washing procedures. However, it has not been demonstrated the bio-compatibility in the detection of cellular microRNAs and circulating microRNAs. Therefore, in this dissertation, I focus on the detection of microRNAs by ExIRMS in cells as well as body fluid.
Firstly, the exchange reaction between the target microRNA and the probe with one mismatched base during competitive binding with the complementary magnetically labelled RNA was utilized. The results showed that ExIRMS was sufficiently robust to achieve a high sensitivity with 105 molecules for detecting microRNAs in cell lysate as well as clinical serum. Neither purification nor amplification are required for detection, which maximally simplify the analysis process and avoid possible loss during sample preparation for absolute quantification. Additionally, this technique was compared with conventional method, and it is confirmed that ExIRMS is comparable to qPCR for purified RNA from both cells and sera. Moreover, accurate absolute quantification of circulating microRNAs requires serum with fractionation and appropriate treatment such as proteinase K and Triton X100 was demonstrated.
Further, ExIRMS was evaluated and optimized for specificity and sensitivity. It was demonstrated that new mismatch (G-U) at position 19 is able to distinguish let-7a from other paralogs of let-7 while old mismatch (C-C) can detect all let-7a family in an energy-based preference. By titration, it was also determined that 1 pM of mismatched-strand with 6 pM of let-7a complement plus 250 thousands of beads was optimal for the platform. In addition, force spectrum was applied prior to ExIRMS to remove non-specific interaction on the surface. Together, the evaluation and optimization provided us a promising future of ExIRMS in microRNAs profiling, which can be further applied in disease diagnosis and prognosis.Biology and Biochemistry, Department o
Abstract 2995: Development of a novel highly potent TLR8 selective agonist for cancer immunotherapy
Abstract
The cancer drug discovery field is experiencing unprecedented revolution accompanied by growing excitement from researchers, drug developers, patients and investors, partly due to recent clinical success of cancer immunotherapy. Human immune defense system comprises both innate and adaptive immune pathways. All the targets drugged by the recently approved cancer immunotherapeutic agents including the immune checkpoint proteins PD-1, PD-L1 and CTLA-4 function in adaptive immune pathways. In contrast, targets involved in the innate immune pathway have not matured to regulatory approval for systemic use though several candidates are now in preclinical and clinical development. Drugs targeting innate immunity represent great opportunity for more rapid and broader spectrum anti-cancer effect than adaptive immunity. Furthermore, combinations of drugs targeting innate and adaptive immunity are expected to produce strong synergistic efficacy owing to their complementary nature as body’s immune defense. Toll-like receptors (TLRs) are a family of proteins that recognize pathogen associated molecular patterns (PAMPs). Their primary function is to activate innate immune responses while also involved in facilitating adaptive immune responses. Different TLRs exert distinct functions by activating varied immune cascades. TLR8 is more broadly expressed in immune cells than other TLRs such as TLR7 and TLR9. One of the major causes of cancer immunotherapy failure is potent suppression of immune response by Treg cells. TLR8 is the only TLR that has been shown to be necessary and sufficient to reverse the suppressive function of Treg cells leading to strong tumor inhibition. Therefore, agonists targeting TLR8 are expected to be effective cancer therapy. However, there is no approved TLR8 selective agonist at present. There is only one TLR8 selective agonist in clinical development. Through structure-based drug design, we discovered a novel, highly potent and selective small molecule TLR8 agonist, DN-A1. DN-A1 exhibited strong in vitro cellular activity with EC50 at 4.23 nM, about 30-fold more potent than the only drug candidate in clinical trials. The activity was highly selective for TLR8 over other TLRs. DN-A1 displayed superior in vitro ADMET and in vivo PK profiles. DN-A1 showed clean CYP profile with IC50 over 10 μM for all major CYP isoenzymes tested including 3A4, 1A2, 2C9, 2C19 and 2D6. DN-A1 had favorable hERG parameter with IC50 over 30 μM whereas the reference compound’s hERG IC50 was 3.84 μM suggesting potential cardiac toxicity. DN-A1 significantly impeded tumor growth as a single agent and was well-tolerated in mouse tumor models. Taken together, DN-A1 warrants further development as a potential best-in-class preclinical drug candidate for TLR8-mediated cancer immunotherapy.
Citation Format: Yuxun Wang, Heping Yang, Longsheng Wang, Guangliang Fu, Fang Bao, Fang Liu, Shuwen Ren, Huanping Li, Haixia Ji, Yajun Yu, Zhiheng Wu, Panhu Zhu, Hui Xu, Yaqiao Gao, Pei Wang, Shoujun Chen, Daxin Gao. Development of a novel highly potent TLR8 selective agonist for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2995. doi:10.1158/1538-7445.AM2017-2995</jats:p
In-sensor reservoir computing for language learning via two-dimensional memristors
© 2021 The Authors.The dynamic processing of optoelectronic signals carrying temporal and sequential information is critical to various machine learning applications including language processing and computer vision. Despite extensive efforts to emulate the visual cortex of human brain, large energy/time overhead and extra hardware costs are incurred by the physically separated sensing, memory, and processing units. The challenge is further intensified by the tedious training of conventional recurrent neural networks for edge deployment. Here, we report in-sensor reservoir computing for language learning. High dimensionality, nonlinearity, and fading memory for the in-sensor reservoir were achieved via two-dimensional memristors based on tin sulfide (SnS), uniquely having dual-type defect states associated with Sn and S vacancies. Our in-sensor reservoir computing demonstrates an accuracy of 91% to classify short sentences of language, thus shedding light on a low training cost and the real-time solution for processing temporal and sequential signals for machine learning applications at the edge.11Nsciescopu
NOx emission and its reduction mechanism investigation in one diffusion-like vortex-tube combustor
In order to overcome the instability of ultra-lean combustion, a novel vortex-tube combustor with axial fuel injection was proposed. The stability limit, flame configuration, NOx emissions, and burn-off rate of the combustor were investigated experimentally under various global equivalence ratios (phi(g)) and fuel flow rates (q(f)). Results show that the combustor exhibits a large stability limit with phi(g) and q(f) as low as 0.01 and 6 x 10(-5) m(3)/s respectively. Complete combustion and ultra-low NOx emissions of less than 3 ppm can be achieved at phi(g) of 0.3 and q(f) of more than 30 x 10(-5) m(3)/s, indicating that the combustor has a good potential for ultra-lean combustion and low NOx emission. The pressure fluctuation amplitude is always less than 1300 Pa during the entire experiments. The vortex-induced flame has a diffusion-like flame structure, which provides a suitable equivalence ratio zone under ultra-lean conditions, whilst the high peak combustion temperature indicates an intensified combustion, which is responsible for the large stability limit and low-pressure fluctuation amplitude. Subsequently, the enhanced stabilization can enable the ultra-lean combustion and the ensued low temperature to conduct, whilst the vortex-flow can decrease the local flow velocity and enable the turbulent diffusion velocity of NO to be dominant, which can make the NO emission reduced further. The decreased area of high-temperature region and the appearance of the negative reaction rate region of NO is the essential reason for the decrease of the NO emission at lean cases. (C) 2020 Elsevier Ltd. All rights reserved
Aerobic exercise can ameliorate heart function in patients with myocardial infarction through up-regulating M3 receptor
AbstractObjective cardioprotective effect and mechanism of exercise training up-regulating the expression of M3 receptor on myocardial infarction. Methods 48 male Sprague-Dawley rats were randomly assigned to three groups (n=16, per group):control group (C), myocardial infarction group (MI), moderate-intensity aerobic exercise with myocardial infarction group (ME). Rats in C group were breed normally. MI was induced by ligation of the left anterior descending (LAD) coronary artery in MI group. Rats in ME group took treadmill exercise for 8weeks. after 1week post-operation. ME group running began at the speed of 10m/min for 5min, then accelerated from 3m/min to 16m/min. The total time of ME is 60min, 5d/week, for 8weeks. LVSP, LVEDP, ±dp/dtmax and the cardiac function changes were measured after training. Myocardial collagen fibers were observed histological section and Masson staining. The expression of myocardial M3 R was observed and analyzed by immunofluorescence. The myocardial protein content of M3 R, MEK1/2,P-ERK1/2,ERK1/2 and apoptosis related Bcl-2 and Bax was assayed by Western blot. Results Compared with the C group, MI increased CVF and LVEDP (P˂0.01), but decreased LVSP and −dp/dtmax (P˂0.01). After MI myocardial M3 positive staining, after MI M3 protein expression significantly higher compared with the C group (P˂0.01), MEK1/2,P-ERK1/2/ERK1/2 protein expression were significantly increased compared with the C group (P˂0.01, P˂0.01), after the MI the Bcl-2/Bax expression significantly reduced compared with the C group (P˂0.01). ME group CVF%, LVEDP significantly reduced compared with the MI group (P˂0.01), but −dp/dtmax significantly increased (P˂0.01). ME group was identified myocardial M3, compared with the MI group, M3 protein expression significantly increased (P˂0.01), but Bcl-2/Bax expression significantly reduced (P˂0.01). Conclusions moderate-intensity aerobic exercise can up-regulated the M3 R-MEK1/2-ERK1/2 signaling pathway, thus inhibit the apoptosis of myocardial cells, reduced myocardial interstitial fibrosis and promote cardiac function after MI
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