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1.
Based on the structure of a de novo designed miniprotein (LCB1) in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, we have generated and characterized truncated peptide variants of LCB1, which present only two of the three LCB1 helices, and which fully retained the virus neutralizing potency against different SARS-CoV-2 variants of concern (VOC). This antiviral activity was even 10-fold stronger for a cyclic variant of the two-helix peptides, as compared to the full-length peptide. Furthermore, the proteolytic stability of the cyclic peptide was substantially improved, rendering it a better potential candidate for SARS-CoV-2 therapy. In a more mechanistic approach, the peptides also served as tools to dissect the role of individual mutations in the RBD for the susceptibility of the resulting virus variants to neutralization by the peptides. As the peptides reported here were generated through chemical synthesis, rather than recombinant protein expression, they are amenable to further chemical modification, including the incorporation of a wide range of non-proteinogenic amino acids, with the aim to further stabilize the peptides against proteolytic degradation, as well as to improve the strength, as well the breadth, of their virus neutralizing capacity.  相似文献   
2.
We propose a concept of holographic data storage which promises storage capacities of more than 100-Gbyte on a digital versatile disk (DVD)-sized disk. The information is stored bitwise in form of microscopic reflection holograms. High storage densities can be achieved by combining multiplexing methods and multilayer storage. A theoretical model for microscopic reflection holograms generated by focused Gaussian beams is proposed. Experimental results are presented for the recording and characterization of microholograms in DuPont's HRF-800 photopolymers. The local distribution of the diffraction efficiency was investigated by applying a confocal scanning microscope setup. Single-color holograms with a radius of 1.8 and 12 μm depth have been recorded. We observe a blue shift in the spectral response of the microholograms of less than 2% due to shrinkage of the polymer. In the case of threefold wavelength multiplexing, all wavelengths are clearly resolved in the spectral response having spectral width Δλ of less than 10 nm (FWHM). Baking the holograms for 1 h at 120°C nearly doubted the diffraction efficiency while the spectral response of the microholograms broadened by a factor two. We showed that 80-ps pulses are sufficient for holographic recording in the photopolymers. An optimized pre-illumination allows a significant increase in diffraction efficiency  相似文献   
3.
We present measurements on an aperiodic device-specific longitudinal-mode pattern in InGaN laser diodes. The characteristic shape of this pattern occurs only if the laser is driven slightly above threshold; in addition, it tunes with temperature at exactly the same rate as the cavity modes. By careful selection of the collection optics and averaging ten rapid scans over 15 min in a high-resolution Fourier transform spectrometer, we could exclude possible explanations like beating of mode families, self-pulsation, or external reflections. A naive simulation of the longitudinal modes profiting from their individual "gain profile" along the cavity suggests that we see the signature of quantum-well thickness fluctuations.  相似文献   
4.
报道了工作在1341 nm的激光二极管(LD)纵向抽运主被动锁模Nd∶YAP激光器。该激光器采用Nd∶YAP晶体作为增益介质,可饱和吸收体V3+∶YAG作为被动锁模器件,声光调制器作为主动锁模器件。在抽运能量50 mJ,抽运频率10 Hz的情况下获得了0.82 mJ的脉冲串输出。该脉冲串的半峰全宽为570 ns,每个脉冲间的间隔为7.7 ns,共包含约75个脉冲,单脉冲的平均能量为11μJ。采用电光晶体RbTiOPO4(RTP)作腔倒空,获得了能量为160μJ,脉宽为680 ps的单脉冲输出。采用InGaAs红外探测器测得光斑大小约为1.2 mm,激光传播因子M2约为1.5。  相似文献   
5.
An efficient synthetic route to pure, high molecular weight poly(p-hydroxystyrene) is reported. The route involves synthesis of a new monomer, p-tert-butoxycarbonyloxystyrene, polymerization by radical initiation or by cationic initiation in liquid SO2, followed by thermolysis or acidolysis of the tert-butoxycarbonyl protecting group. Porous, crosslinked resin beads containing the nucleophilic, phenol pendant group have been prepared in a similar fashion from the precursor terpolymer of p-tert-butoxycarbonyloxystyrene, styrene and divinylbenzene. The utility of this resin for solid-phase synthesis has been demonstrated.  相似文献   
6.
To facilitate efficient drug delivery to tumor tissue, several nanomaterials have been designed, with combined diagnostic and therapeutic properties. In this work, we carried out fundamental in vitro and in vivo experiments to assess the labeling efficacy of our novel theranostic nanoprobe, consisting of glycogen conjugated with a red fluorescent probe and gadolinium. Microscopy and resazurin viability assays were used to study cell labeling and cell viability in human metastatic melanoma cell lines. Fluorescence lifetime correlation spectroscopy (FLCS) was done to investigate nanoprobe stability. Magnetic resonance imaging (MRI) was performed to study T1 relaxivity in vitro, and contrast enhancement in a subcutaneous in vivo tumor model. Efficient cell labeling was demonstrated, while cell viability, cell migration, and cell growth was not affected. FLCS showed that the nanoprobe did not degrade in blood plasma. MRI demonstrated that down to 750 cells/μL of labeled cells in agar phantoms could be detected. In vivo MRI showed that contrast enhancement in tumors was comparable between Omniscan contrast agent and the nanoprobe. In conclusion, we demonstrate for the first time that a non-toxic glycogen-based nanoprobe may effectively visualize tumor cells and tissue, and, in future experiments, we will investigate its therapeutic potential by conjugating therapeutic compounds to the nanoprobe.  相似文献   
7.
The broadly neutralizing HIV‐1 antibody b12 recognizes the CD4 binding site of the HIV‐1 envelope glycoprotein gp120 and efficiently neutralizes HIV‐1 infections in vitro and in vivo. Based on the 3D structure of a b12 ? gp120 complex, we have designed an assembled peptide (b12‐M) that presents the parts of the three heavy‐chain complementarity‐determining regions (CDRs) of b12, which contain the contact sites of the antibody for gp120. This b12‐mimetic peptide, as well as a truncated peptide presenting only two of the three heavy‐chain CDRs of b12, were shown to recognize gp120 in a similar manner to b12, as well as to inhibit HIV‐1 infection, demonstrating functional mimicry of b12 by the paratope mimetic peptides.  相似文献   
8.
A wide range of parameters was investigated by numerical calculations concerning their impact on DC stray current corrosion of reinforced concrete (RC) structures. A simplified model geometry was used to extract the relevant parameters and their interaction in terms of stray current-affected structures. This study mainly focuses on RC structures that are fitted with cathodic protection installations. The findings reveal a complex interaction between the investigated parameters. The possible relevance of further parameters, which is not the subject of this study, was emphasised.  相似文献   
9.
10.
The frequency of one axial mode of a three-mode He/Ne laser can be tuned independently from the other modes if a third mirror is added to the usual two laser mirrors. Provided the adjustment is correct, the frequency shift is proportional to a change of the optical path length between the third mirror and the neighboring laser mirror. By observing the beat frequency of the laser, measurements of optical path variations down to 10-5Å are possible.  相似文献   
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