By designing a structured gas density profile between the dual-stage gas jets to manipulate electron seeding and energy chirp reversal for compressing the energy spread, we have experimentally ...produced high-brightness high-energy electron beams from a cascaded laser wakefield accelerator with peak energies in the range of 200-600 MeV, 0.4%-1.2% rms energy spread, 10-80 pC charge, and ∼0.2 mrad rms divergence. The maximum six-dimensional brightness B_{6D,n} is estimated as ∼6.5×10^{15} A/m^{2}/0.1%, which is very close to the typical brightness of e beams from state-of-the-art linac drivers. These high-brightness high-energy e beams may lead to the realization of compact monoenergetic gamma-ray and intense coherent x-ray radiation sources.
Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) ...metastasis and chemoresistance have not been fully characterized.
CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1.
CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/β-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients.
CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.
We use correlated confocal and wide-field fluorescence microscopy to probe the interplay between local variations in charge carrier recombination and charge carrier transport in methylammonium lead ...triiodide perovskite thin films. We find that local photoluminescence variations present in confocal imaging are also observed in wide-field imaging, while intensity-dependent confocal measurements show that the heterogeneity in nonradiative losses observed at low excitation powers becomes less pronounced at higher excitation powers. Both confocal and wide-field images show that carriers undergo anisotropic diffusion due to differences in intergrain connectivity. These data are all qualitatively consistent with trap-dominated variations in local photoluminescence intensity and with grain boundaries that exhibit varying degrees of opacity to carrier transport. We use a two-dimensional kinetic model to simulate and compare confocal time-resolved photoluminescence decay traces with experimental data. The simulations further support the assignment of local variations in nonradiative recombination as the primary cause of photoluminescence heterogeneity in the films studied herein. These results point to surface passivation and intergrain connectivity as areas that could yield improvements in perovskite solar cells and optoelectronic device performance.
We report on near-GeV electron beam generation from an all-optical cascaded laser wakefield accelerator (LWFA). Electron injection and acceleration are successfully separated and controlled in ...different LWFA stages by employing two gas cells filled with a He/O2 mixture and pure He gas, respectively. Electrons with a Maxwellian spectrum, generated from the first LWFA assisted by ionization-induced injection, were seeded into the second LWFA with a 3-mm-thick gas cell and accelerated to be a 0.8-GeV quasimonoenergetic electron beam, corresponding to an acceleration gradient of 187 GV/m. The demonstrated scheme paves the way towards the multi-GeV laser accelerators.
Using density functional theory combined with a semiempirical van der Waals dispersion correction, we have investigated the stability of lattice defects including boron vacancy, substitutional and ...interstitial X (X = H, C, B, N, O), and Σ5 tilt grain boundaries in borophene and their influence on the anisotropic mechanical properties of this two-dimensional system. The pristine borophene has significant in-plane Young’s moduli and Poisson’s ratio anisotropy due to its strong and highly coordinated B–B bonds. The concentration of B vacancy and Σ5 grain boundaries could be rather high given that their formation energies are as low as 0.10 and 0.06 eV/Å, respectively. In addition, our results also suggest that borophene can react easily with H2, O2, and N2 when exposed to these molecules. We find that the mechanical strength of borophene is remarkably reduced by these defects. The anisotropy in Poisson’s ratio, however, can be tuned by some of them. Furthermore, the adsorbed H or substitutional C may induce negative Poisson’s ratio in borophene, and the substitutional C or N can significantly increase the Poisson’s ratio by constrast.
The amount of data produced and communicated over the Internet is significantly increasing, thereby creating challenges for the organizations that would like to reap the benefits from analyzing this ...massive influx of big data. This is because big data can provide unique insights into, inter alia, market trends, customer buying patterns, and maintenance cycles, as well as into ways of lowering costs and enabling more targeted business decisions. Realizing the importance of big data business analytics (BDBA), we review and classify the literature on the application of BDBA on logistics and supply chain management (LSCM) – that we define as supply chain analytics (SCA), based on the nature of analytics (descriptive, predictive, prescriptive) and the focus of the LSCM (strategy and operations). To assess the extent to which SCA is applied within LSCM, we propose a maturity framework of SCA, based on four capability levels, that is, functional, process-based, collaborative, agile SCA, and sustainable SCA. We highlight the role of SCA in LSCM and denote the use of methodologies and techniques to collect, disseminate, analyze, and use big data driven information. Furthermore, we stress the need for managers to understand BDBA and SCA as strategic assets that should be integrated across business activities to enable integrated enterprise business analytics. Finally, we outline the limitations of our study and future research directions.
We present fast functional photoacoustic microscopy (PAM) for three-dimensional high-resolution, high-speed imaging of the mouse brain, complementary to other imaging modalities. We implemented a ...single-wavelength pulse-width-based method with a one-dimensional imaging rate of 100 kHz to image blood oxygenation with capillary-level resolution. We applied PAM to image the vascular morphology, blood oxygenation, blood flow and oxygen metabolism in both resting and stimulated states in the mouse brain.
Aim
After extended left colectomy, traditional colorectal anastomosis is often not feasible because of insufficient length of the remaining colon to perform a tension‐free anastomosis. Total ...colectomy with ileorectal anastomosis could be an alternative but this can lead to unsatisfactory quality of life. Trans‐mesenteric colorectal anastomosis or inverted right colonic transposition (the so‐called Deloyers procedure) are two possible solutions for creating a tension‐free colorectal anastomosis after extended left colectomy. Few studies have reported their results of these two techniques and mostly via laparotomy. The aim of this study was to describe the trans‐mesenteric colorectal anastomosis and the inverted right colonic transposition procedure via a laparoscopic approach and report the outcome in a series of 13 consecutive patients.
Method
This was retrospective chart review of laparoscopic colorectal surgery with trans‐mesenteric colorectal anastomosis or the inverted right colonic transposition procedure from January 2015 up to 2019. An accompanying video demonstrates these two techniques.
Results
Thirteen consecutive patients underwent either a laparoscopic trans‐mesenteric colorectal anastomosis (n = 9) or an inverted right colonic transposition procedure (n = 4). One patient had intra‐operative presacral bleeding that was stopped successfully without conversion. Two patients had a postoperative intra‐abdominal abscess, but no anastomotic complications were recorded. The median number of bowel movements per day after 6 months was 2 (range 2–5).
Conclusions
Trans‐mesenteric colorectal anastomosis or the inverted right colonic transposition procedure is feasible laparoscopically. The now well‐established classical advantages of the laparoscopic approach are associated with good functional outcome after these procedures.
Abstract Although anti−cancer immuno−based combinatorial therapeutic approaches have shown promising results, efficient tumour eradication demands further intensification of anti−tumour immune ...response. With the emerging field of nanovaccinology, multi−walled carbon nanotubes (MWNTs) have manifested prominent potentials as tumour antigen nanocarriers. Nevertheless, the utilization of MWNTs in co−delivering antigen along with different types of immunoadjuvants to antigen presenting cells (APCs) has not been investigated yet. We hypothesized that harnessing MWNT for concurrent delivery of cytosine−phosphate−guanine oligodeoxynucleotide (CpG) and anti-CD40 Ig (αCD40), as immunoadjuvants, along with the model antigen ovalbumin (OVA) could potentiate immune response induced against OVA−expressing tumour cells. We initially investigated the effective method to co−deliver OVA and CpG using MWNT to the APC. Covalent conjugation of OVA and CpG prior to loading onto MWNTs markedly augmented the CpG−mediated adjuvanticity, as demonstrated by the significantly increased OVA−specific T cell responses in vitro and in C57BL/6 mice. αCD40 was then included as a second immunoadjuvant to further intensify the immune response. Immune response elicited in vitro and in vivo by OVA, CpG and αCD40 was significantly potentiated by their co−incorporation onto the MWNTs. Furthermore, MWNT remarkably improved the ability of co−loaded OVA, CpG and αCD40 in inhibiting the growth of OVA−expressing B16F10 melanoma cells in subcutaneous or lung pseudo−metastatic tumour models. Therefore, this study suggests that the utilization of MWNTs for the co−delivery of tumour−derived antigen, CpG and αCD40 could be a competent approach for efficient tumours eradication.
PDF
