The immunogenicity of HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) peptide in severe acute respiratory syndrome coronavirus (SARS-CoV) nuclear capsid (N) and spike (S) proteins was determined by testing the proteins' ability to elicit a specific cellular immune response after immunization of HLA-A2.1 transgenic mice and in vitro vaccination of HLA-A2.1 positive human peripheral blood mononuclearcytes (PBMCs). First, we screened SARS N and S amino acid sequences for allele-specific motif matching those in human HLA-A2.1 MHC-I molecules. From HLA peptide binding predictions (http://thr.cit.nih.gov/molbio/hla_bind/), ten each potential N- and S-specific HLA-A2.1-binding peptides were synthesized. The high affinity HLA-A2.1 peptides were validated by T2-cell stabilization assays, with immunogenicity assays revealing peptides N223-231, N227-235, and N317-325 to be the first identified HLA-A*0201-restricted CTL epitopes of SARS-CoV N protein. In addition, previous reports identified three HLA-A*0201-restricted CTL epitopes of S protein (S978-986, S1203-1211, and S1167-1175), here we found two novel peptides S787-795 and S1042-1050 as S-specific CTL epitopes. Moreover, our identified N317-325 and S1042-1050 CTL epitopes could induce recall responses when IFN-gamma stimulation of blood CD8+ T-cells revealed significant difference between normal healthy donors and SARS-recovered patients after those PBMCs were in vitro vaccinated with their cognate antigen. Our results would provide a new insight into the development of therapeutic vaccine in SARS.
Graded index (GRIN) lenses are commonly used for compact imaging systems. It is not widely appreciated that the ion-exchange process that creates the rotationally symmetric GRIN lens index profile also causes a symmetric birefringence variation. This property is usually considered a nuisance, such that manufacturing processes are optimized to keep it to a minimum. Here, rather than avoiding this birefringence, we understand and harness it by using GRIN lenses in cascade with other optical components to enable extra functionality in commonplace GRIN lens systems. We show how birefringence in the GRIN cascades can generate vector vortex beams and foci, and how it can be used advantageously to improve axial resolution. Through using the birefringence for analysis, we show that the GRIN cascades form the basis of a new single-shot Müller matrix polarimeter with potential for endoscopic label-free cancer diagnostics. The versatility of these cascades opens up new technological directions.
Fibrotic diseases cause annually more than 800,000 deaths worldwide, where of the majority accounts for cardiovascular fibrosis, which is characterized by endothelial dysfunction, myocardial stiffening and reduced dispensability. MicroRNAs (miRs), small noncoding RNAs, play critical roles in cardiovascular dysfunction and related disorders. Intriguingly, there is a critical link among miR-122, cardiovascular fibrosis, sirtuin 6 (SIRT6) and angiotensin-converting enzyme 2 (ACE2), which was recently identified as a coreceptor for SARS-CoV2 and a negative regulator of the rennin-angiotensin system. MiR-122 overexpression appears to exacerbate the angiotensin II-mediated loss of autophagy and increased inflammation, apoptosis, extracellular matrix deposition, cardiovascular fibrosis and dysfunction by modulating the SIRT6-Elabela-ACE2, LGR4-β-catenin, TGFβ-CTGF and PTEN-PI3K-Akt signaling pathways. More importantly, the inhibition of miR-122 has proautophagic, antioxidant, anti-inflammatory, anti-apoptotic and antifibrotic effects. Clinical and experimental studies clearly demonstrate that miR-122 functions as a crucial hallmark of fibrogenesis, cardiovascular injury and dysfunction. Additionally, the miR-122 level is related to the severity of hypertension, atherosclerosis, atrial fibrillation, acute myocardial infarction and heart failure, and miR-122 expression is a risk factor for these diseases. The miR-122 level has emerged as an early-warning biomarker cardiovascular fibrosis, and targeting miR-122 is a novel therapeutic approach against progression of cardiovascular dysfunction. Therefore, an increased understanding of the cardiovascular roles of miR-122 will help the development of effective interventions. This review summarizes the biogenesis of miR-122; regulatory effects and underlying mechanisms of miR-122 on cardiovascular fibrosis and related diseases; and its function as a potential specific biomarker for cardiovascular dysfunction.
Robot-assisted deployment of fenestrated stent grafts in Fenestrated Endovascular Aortic Repair (FEVAR) requires accurate geometrical alignment. Currently, this process is guided by 2D fluoroscopy which is uninformative and error prone. In this paper, a real-time framework is proposed to instantiate the 3D shape of a fenestrated stent graft utilizing only a single low-dose 2D fluoroscopic image. Firstly, markers were placed on the fenestrated stent graft. Secondly, the 3D pose of each stent segment was instantiated by the RPnP (Robust Perspective-n-Point) method. Thirdly, the 3D shape of the whole stent graft was instantiated via graft gap interpolation. Focal U-Net was proposed to segment the markers from 2D fluoroscopic images to achieve semi-automatic marker detection. The proposed framework was validated on five patient-specific 3D printed aortic aneurysm phantoms and three stent grafts with new marker placements, showing an average distance error of 1 − 3mm and an average angular error of 4 • .
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