The coronavirus disease 2019 (COVID-19) pandemic presents an urgent health crisis. Human neutralizing antibodies that target the host ACE2 receptor-binding domain (RBD) of the severe acute ...respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein
show promise therapeutically and are being evaluated clinically
. Here, to identify the structural correlates of SARS-CoV-2 neutralization, we solved eight new structures of distinct COVID-19 human neutralizing antibodies
in complex with the SARS-CoV-2 spike trimer or RBD. Structural comparisons allowed us to classify the antibodies into categories: (1) neutralizing antibodies encoded by the VH3-53 gene segment with short CDRH3 loops that block ACE2 and bind only to 'up' RBDs; (2) ACE2-blocking neutralizing antibodies that bind both up and 'down' RBDs and can contact adjacent RBDs; (3) neutralizing antibodies that bind outside the ACE2 site and recognize both up and down RBDs; and (4) previously described antibodies that do not block ACE2 and bind only to up RBDs
. Class 2 contained four neutralizing antibodies with epitopes that bridged RBDs, including a VH3-53 antibody that used a long CDRH3 with a hydrophobic tip to bridge between adjacent down RBDs, thereby locking the spike into a closed conformation. Epitope and paratope mapping revealed few interactions with host-derived N-glycans and minor contributions of antibody somatic hypermutations to epitope contacts. Affinity measurements and mapping of naturally occurring and in vitro-selected spike mutants in 3D provided insight into the potential for SARS-CoV-2 to escape from antibodies elicited during infection or delivered therapeutically. These classifications and structural analyses provide rules for assigning current and future human RBD-targeting antibodies into classes, evaluating avidity effects and suggesting combinations for clinical use, and provide insight into immune responses against SARS-CoV-2.
Birman–Hilden Bundles. I Malyutin, A. V.
Siberian mathematical journal,
2024/1, Letnik:
65, Številka:
1
Journal Article
Recenzirano
A topological fibered space is a Birman–Hilden space whenever in each isotopic pair of its fiber-preserving (taking each fiber to a fiber) self-homeomorphisms the homeomorphisms are also ...fiber-isotopic (isotopic through fiber-preserving homeomorphisms). We present a series of sufficient conditions for a fiber bundle over the circle to be a Birman–Hilden space.
Birman–Hilden Bundles. II Malyutin, A. V.
Siberian mathematical journal,
03/2024, Letnik:
65, Številka:
2
Journal Article
Recenzirano
We study the structure of self-homeomorphism groups of fibered manifolds. A fibered topological space is a Birman–Hilden space whenever in each isotopic pair of its fiber-preserving (taking each ...fiber to a fiber) self-homeomorphisms the homeomorphisms are also fiber-isotopic (isotopic through fiber-preserving homeomorphisms). We prove in particular that the Birman–Hilden class contains all compact connected locally trivial surface bundles over the circle, including nonorientable ones and those with nonempty boundary, as well as all closed orientable Haken 3-manifold bundles over the circle, including nonorientable ones.
A classical theorem of braid theory, dating back to Artin’s work, says that two closed braids in a solid torus are ambient isotopic if and only if they represent the same conjugacy class of the braid ...group. This theorem can be reformulated in the framework of link theory without referring to the group structure. A link in a surface bundle over the circle is transversal whenever it covers the circle. In this terminology, Artin’s theorem states that in a solid torus trivially fibered over the circle transversal links are ambient isotopic if and only if they are isotopic in the class of transversal links. We generalize this result by proving that (in the piecewise linear category) transversal links in an arbitrary compact orientable
-manifold fibered over the circle with a compact fiber are ambient isotopic if and only if they are isotopic in the class of transversal links.
Magnesium alloys are used in aircraft because of their light weight. However, for these alloys to be applied in electronic devices, high thermal conductivities are required. Several high-potential ...compositions of Mg–Zn–Y–Zr alloys were selected by phase composition and their freezing ranges calculated using Thermo-Calc software. The alloys were prepared, and their fluidity, hot tearing susceptibility, mechanical properties, and thermal conductivity were obtained and compared. The alloy composed of Mg–4 wt% Zn–3 wt% Y–0.3 wt% Zr was selected for further investigation, because of its high thermal conductivity and satisfactory mechanical properties. The Mg–4 wt% Zn–3 wt% Y–0.3 wt% Zr alloy's fluidity and hot tearing susceptibility were similar to those of the widespread AZ91 commercial casting magnesium alloy. The influence of a heat treatment regime on the microstructure, thermal conductivity, and mechanical properties of the developed alloy was also investigated. It was established that the room temperature thermal conductivity of the Mg–4 wt% Zn–3 wt% Y–0.3 wt% Zr alloy after aging at 300 °C for 5 h was 105 W/mK. Additionally, the following tensile test results were obtained in aged condition: 120 MPa yield strength, 200 MPa ultimate tensile strength, and 4% elongation. The utilization of solid solution heat treatment at 520 °C for 8 h prior to aging can promote up to 9% increase in elongation. The Mg–4 wt% Zn–3 wt% Y–0.3 wt% Zr casting alloy can be used as a high thermal conductivity material with industrial applications.
We considered the propagation of a short pulse in the picosecond range in coupled lines with a ratio of phase velocities of anti-phase and in-phase waves of 3:1. We showed experimentally a special ...aspect in the interference of in-phase and anti-phase waves in such structures, which leads to the input pulse separation between three ports without a significant energy loss associated with the reflection from the input. The wave interference was found to lead to a change in the directional properties of the structures under consideration and a separation of the pulse spectral components between the ports.
Introduction.
Available information on the occurrences of high alkaline magmatic rocks fixing the position of the western flanks of the southern branches (Gobi Altai and Gobi Tien-Shan) of the ...Central Asian Late Paleozoic continental rift system in the territory of the North-West of Chingiz (the eastern part of Central Kazakhstan), the Kendyktas-Chu-Ili-Bet-Pak-Dal uranium-bearing province of the Southern Kazakhstan and the Chatkal-Naryn zone of Tien-Shan (Uzbekistan) is reviewed. Data on the confinement of uranium mineralization to these occurrences and its paragenetic relationship with the Late Paleozoic alkaline volcanic-plutonic association is provided.
Aim.
To study the uranium mineralization of Late Paleozoic alkaline magmatism to clarify metallogenic representations and justify prospects for the ore-bearingness of the western flanks of the southern branches of the Central Asian continental rift system.
Materials and methods.
The largest part of materials was obtained in the process of geological surveys and prospecting works of various scales in the regions of Central Kazakhstan in the period 1965–1985 with the participation of the author. Published materials concerning the subdivision of magmatic formations in the uranium ore fields of Southern Kazakhstan and the Chatkal-Naryn zone were also used.
Results.
Subvolcanic bodies of comendites and small masses of alkaline granites of the Late Paleozoic were identified across the area of uranium ore occurrences in the South-Western Chingiz and some deposits of South Kazakhstan confined to Devonian volcanic structures, which indicates their relationship with the southern branches of the Central Asian continental rift system. Rare-metalalbite, uranium-phosphorus and uranium-molybdenum formations are confined to alkaline rocks. Rare-metal mineralization is closely associated with alkaline rocks, while uranium mineralization occurred after the introduction of the most recent microgabbrodiorite and lamprophyre dikes. Similar correlations of rare-metal and uranium mineralization with alkaline granites and of microgabbrodiorite and lamprophyre dikes are observed in the uranium deposits of the Chatkal-Naryn zone located among the early Permian bimodal trachybasalt-trachyolite formation.
Conclusion.
The establishment of ore mineralization on the western flanks of the Gobi Altai and Gobi Tien-Shan branches in the territory of Southern and Central Kazakhstan allows these areas to be distinguished as metallogenic zones, promising in terms of rare-metal and uranium mineralization.
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An analysis of modeling the mineralization zones of stockwork ore deposits indicates that the inclusion of barren rocks in a mineralization zone has little effect on the downward bias of the ...component content estimates. On the contrary, the extreme component contents that often occur among the exploration data influence the bias of component content estimates in an upward manner, i.e., its overestimation.
Magnesium alloys are commonly used to produce lightweight parts. While most magnesium alloys exhibit low thermal conductivities, high thermal conductivities are needed for electronic devices. In this ...study, we attempted to develop new magnesium casting alloys with high thermal conductivities. The MgZnSiCa alloy compositions were chosen using CALPHAD (CALculation of PHAse Diagrams) calculations, and alloy samples were prepared. The fluidity and hot-tearing resistance were measured. The results indicated that these properties were similar to those of AZ91 alloy. Tensile tests showed that high-pressure die casting could produce MgZnSiCa alloys possessing mechanical properties 1.5–3 times higher than those produced via sand casting. The alloy thermal conductivity was 126 W/mK at room temperature. The corrosion rates of the as-cast samples in NaCl/water solutions were two times higher than that of AZ91. Keywords: Magnesium alloy, Thermal conductivity, Phase composition, Corrosion rate, Sand casting, High-pressure die casting
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