Roles of host proteases in the entry of SARS-CoV-2

The spike protein(S)of SARS-CoV-2 is responsible for viral attachment and entry,thus a major factor for host suscep-tibility,tissue tropism,virulence and pathogenicity.The S is divided with S1 and S2 region,and the S1 contains the receptor-binding domain(RBD),while the S2 contains the hydrophobic fusion domain for the entry into the host cell.Numerous host proteases have been implicated in the activation of SARS-CoV-2 S through various c leavage sites.In this article,we review host proteases including furin,trypsin,transmembrane protease serine 2(TMPRSS2)and cathepsins in the activation of SARS-CoV-2 S.Many betacoronaviruses including SARS-CoV-2 have polybasic residues at the S1/S2 site which is subjected to the cleavage by furin.The S1/S2 cleavage facilitates more assessable RBD to the receptor ACE2,and the binding triggers further conformational changes and exposure of the S2'site to proteases such as type Il transmembrane serine proteases(TTPRs)including TMPRSS2.In the presence of TMPRSS2 on the target cells,SARS-CoV-2 can utilize a direct entry route by fusion of the viral envelope to the cellular membrane.In the absence of TMPRSS2,SARS-CoV-2 enter target cells via endosomes where multiple cathepsins cleave the S for the successful entry.Additional host proteases involved in the cleavage of the S were discussed.This article also includes roles of 3C-like protease inhibitors which have inhibitory activity against cathepsin L in the entry of SARS-CoV-2,and discussed the dual roles of such inhibitors in virus replication.

Ca^(2+)-induced myelin pathology precedes axonal spheroid formation and is mediated in part by store-operated Ca^(2+)entry after spinal cord injury

The formation of axonal spheroid is a common feature following spinal cord injury.To further understand the source of Ca^(2+)that mediates axonal spheroid formation,we used our previously characterized ex vivo mouse spinal cord model that allows precise perturbation of extracellular Ca^(2+).We performed twophoton excitation imaging of spinal cords isolated from Thy1YFP+transgenic mice and applied the lipophilic dye,Nile red,to record dynamic changes in dorsal column axons and their myelin sheaths respectively.We selectively released Ca^(2+)from internal stores using the Ca^(2+)ionophore ionomycin in the presence or absence of external Ca^(2+).We reported that ionomycin dose-dependently induces pathological changes in myelin and pronounced axonal spheroid formation in the presence of normal 2 m M Ca^(2+)artificial cerebrospinal fluid.In contrast,removal of external Ca^(2+)significantly decreased ionomycin-induced myelin and axonal spheroid formation at 2 hours but not at 1 hour after treatment.Using mice that express a neuron-specific Ca^(2+)indicator in spinal cord axons,we confirmed that ionomycin induced significant increases in intra-axonal Ca^(2+),but not in the absence of external Ca^(2+).Periaxonal swelling and the resultant disruption in the axo-myelinic interface often precedes and is negatively correlated with axonal spheroid formation.Pretreatment with YM58483(500 n M),a well-established blocker of store-operated Ca^(2+)entry,significantly decreased myelin injury and axonal spheroid formation.Collectively,these data reveal that ionomycin-induced depletion of internal Ca^(2+)stores and subsequent external Ca^(2+)entry through store-operated Ca^(2+)entry contributes to pathological changes in myelin and axonal spheroid formation,providing new targets to protect central myelinated fibers.

Experimental observation on water entry of a sphere in regular wave

This paper presents a novel experiment to observe the whole water entry process of a free-falling sphere into a regular wave.A time-accurate synchronizing system modulates the moment elaborately to ensure the sphere impacting onto the water surface at the desirable wave phase.Four high-speed cameras focus locally to measure the high-precision size of the cavity evolution.Meanwhile,the aggregated field view of the camera array covers both the splash above the free surface and the entire cavity in the wave.The detailed methodologies are described and verified for the hardware set-up and the image post-processing.The theoretical maximum deviation is 1.7%on the space scale.The integral morphology of the cavity is captured precisely in the coordinate system during the sphere penetrates through the water at four representative wave phases and the still water.The result shows that the horizontal velocity of the fluid particle in the wave impels the cavity and changes the shape distinctly.Notably,the wave motion causes the cavity to pinch offearlier at the wave trough phase and later at the wave crest phase than in the still water.The wave motion influences the falling process of the sphere slightly in the present parameters.

Eye-shaped keyboard for dual-hand text entry in virtual reality

We propose an eye-shaped keyboard for high-speed text entry in virtual reality (VR), having the shape of dual eyes with characters arranged along the curved eyelids, which ensures low density and short spacing of the keys. The eye-shaped keyboard references the QWERTY key sequence, allowing the users to benefit from their experience using the QWERTY keyboard. The user interacts with an eye-shaped keyboard using rays controlled with both the hands. A character can be entered in one step by moving the rays from the inner eye regions to regions of the characters. A high-speed auto-complete system was designed for the eye-shaped keyboard. We conducted a pilot study to determine the optimal parameters, and a user study to compare our eye-shaped keyboard with the QWERTY and circular keyboards. For beginners, the eye-shaped keyboard performed significantly more efficiently and accurately with less task load and hand movement than the circular keyboard. Compared with the QWERTY keyboard, the eye-shaped keyboard is more accurate and significantly reduces hand translation while maintaining similar efficiency. Finally, to evaluate the potential of eye-shaped keyboards, we conducted another user study. In this study, the participants were asked to type continuously for three days using the proposed eye-shaped keyboard, with two sessions per day. In each session, participants were asked to type for 20min, and then their typing performance was tested. The eye-shaped keyboard was proven to be efficient and promising, with an average speed of 19.89 words per minute (WPM) and mean uncorrected error rate of 1.939%. The maximum speed reached 24.97 WPM after six sessions and continued to increase.

An Innovative Non-Pillar Coal-Mining Technology with Automatically Formed Entry: A Case Study

A non-pillar coal-mining technology with an automatically formed entry is proposed,which reduces the waste of coal resources and the underground entry drivage workload.Three key techniques in this technology cooperate to achieve automatic formation and retaining of the gob-side entry,and to realize nonpillar mining.Constant-resistance large deformation(CRLD)support ensures the stability of the entry roof;directional presplitting blasting(DPB)separates the entry roof and the gob roof;and a blockinggangue support system(BGSS)integrates the caved rock material as an effective entry rib.An industrial test was conducted to verify the engineering effects of these key techniques.The field application results showed that the retained entry was under the pressure-relief zone due to the broken-expansion nature of the caved rock mass within the DPB height.After going through a provisional dynamic pressure-bearing zone,the retained entry entered the stability zone.The final stable entry meets the requirements of safety and production.The research results demonstrate the good engineering applicability of this technology.By taking the framework of the technology design principles into consideration and adjusting the measures according to different site conditions,it is expected that the proposed non-pillar coal-mining technology can be popularized on a large scale.

New insights into store-independent Ca^(2+) entry: secretory pathway calcium ATPase 2 in normal physiology and cancer

Recent studies in secretory pathway calcium ATPases （SPCA） revealed novel functions of SPCA2 in interacting with store-operated Ca2＋ channel Oral I and inducing Ca2＋ influx at the cell surface. Importantly, SPCA2-mediated Ca2＋ signaling is uncoupled from its conventional role of Ca2＋-ATPase and independent of store-operated Ca2＋ signaling pathway. SPCA2-induced store-independent Ca2＋ entry （SICE） plays essential roles in many important physiological processes, while unbalanced SICE leads to enhanced cell proliferation and tumorigenesis. Finally, we have summarized the clinical implication of SICE in oral cancer prognosis and treatment. Inhibition of SICE may be a new target for the development of cancer therapeutics.

Rock burst mechanism analysis in an advanced segment of gob-side entry under different dip angles of the seam and prevention technology

In order to investigate the frequent occurrences of rock burst in gob-side entry during the mining process of the mining zone No. 7, the mechanical model of main roof of fully-mechanized caving mining before breaking was established by the Winkler foundation beam theory, and the stress evolution law of surrounding rock with different dip angles of the seam during the mining process was analyzed by using FLAC3 D. The results show that: with the dip angle changing from 45° to 0°, the solid-coal side of gobside entry begins to form an L-shaped stress concentration zone at a dip angle of 30°, and the stress concentration degree goes to higher and higher levels. However, the stress concentration degree of the coalpillar side goes to lower and lower levels; the influence range and peak stress of the abutment at the lateral strata of adjacent gob increase with dip angle decreasing and reach a maximum value at a dip angle of 0°, but the tailgate is not affected; the abutment pressure superposition of two adjacent gobs leads to stress concentration further enhancing in both sides of gob-side entry. With the influence of strong mining disturbance, rock burst is easily induced by dynamic and static combined load in the advanced segment of gob-side entry. To achieve stability control similar to that in the roadway, the key control strategy is to reinforce surrounding rock and unload both sides. Accordingly, the large-diameter drilling and high-pressure water injection combined unloading and reinforced support cooperative control technology was proposed and applied in field test. The results of Electromagnetic Emission(EME) and field observation showed that unloading and surrounding rock control effect was obvious.

Clogging behavior of submerged entry nozzles for Ti-bearing IF steel

The nozzle clogging behavior of Ti-bearing IF steel was studied by metallographic analysis,scanning electron microscopy（SEM）, energy dispersive spectroscopy（EDS）,and X-ray diffraction（XRD）.According to the experimental results,nozzle clogging primarily appears three layers.There are a lot of large-sized iron particles in the inner layer and mainly slag phase in the middle and outer layers.The principal clog constituents of the inner layer are loose alumina cluster inclusions and granular shaped alumina inclusions,containing iron particles. The clog constituents of the middle layer are mainly dendrite alumina inclusions.The primary phases existing in nozzle clogging are FeO·TiO2 and FeO·Al2O3 besidesα-Al2O3 and a-Fe.The FeO·TiO2 phases among the deposits adhere the deposits together firmly enough to lead to the inferior castability of Ti-bearing ultra low carbon steel compared with that of Ti-free low carbon Al-killed steel.

UNDERWATER ACOUSTICS AND CAVITATING FLOW OF WATER ENTRY

The fluid mechanics of water entry is studied through investigating the underwater acoustics and the supercavitation.Underwater acoustic signals in water entry are extensively measured at about 30 different positions by using a PVDF needle hydrophone.From the measurements we obtain (1)the primary shock wave caused by the impact of the blunt body on free surface;(2)the vapor pressure inside the cavity;(3)the secondary shock wave caused by pulling away of the cavity from free surface;and so on.The supercavitation induced by the blunt body is observed by using a digital high-speed video camera as well as the single shot photography.The periodic and 3 dimensional motion of the supercavitation is revealed.The experiment is carried out at room temperature.

Surrounding rock control of gob-side entry driving with narrow coal pillar and roadway side sealing technology in Yangliu Coal Mine

Gob-side entry driving can increase coal recovery ratio, and it is implied in many coal mines. Based on geological condition of 10416 working face tailentry in Yangliu Coal Mine, the surrounding rock deformation characteristics of gob-side entry driving with narrow coal pillar is analysed, reasonable size of coal pillar and reasonable roadway excavation time after mining are achieved. Surrounding rock control technology and effective roadway side sealing technology are proposed and are taken into field practice. The results showed that a safer and more efficient mining of working face can be achieved. In addition, results of this paper also have important theoretical significance and valuable reference for surrounding rock control technology of gob-side entry driving with narrow coal pillar under special geological condition.

Deformation characteristics and reinforcement technology for entry subjected to mining-induced stresses

The entry at Zhangcun coal mine in Lu＇an coal mining area in Shanxi Province suffered from severe mining-induced stresses with the heading face driven oppositely to an adjacent working face. In this paper, the characteristics of deformation and failure of the entry were investigated in terms of the tempo-spatial relations between heading and working faces through field study and numerical modeling. The three-dimensional （3D） finite difference models were built to investigate stresses, displacements and damages in the surrounding rocks of the entry and the working face. The field study includes selection of reinforcing methods and materials, design parameters, and determination of cable prestress. The monitoring data of entry deformation and stress along the cables during every stage were presented. The state of the reinforced entry was evaluated based on the monitoring data. The results demonstrate that before the heading face of the entry crosses the adjacent working face, the influence of advanced abutment pressure caused by adjacent working face upon the entry is not significant. After they cross each other, however, the lateral abutment pressure will have an evident impact on the entry. The displacement rate of the entry will be greatly increased and reaches a certain value within a certain distance between the heading face and the working face. Then, it will increase again with the presence of secondary mining-induced pressure on the entry when the present working face advances. The fully-grouted cable with short length, high strength and high prestress is an effective way to reinforce the entry suffering from severe mining-induced stresses, which greatly reduces the displacement and failure possibility of the entry. Finally, the principles and recommendations for reinforcing design of entries suffering from severe mining-induced stresses were proposed according to field study, numerical modeling and experiences from other coal mines. Problems encountered in field study and suggestions for reinforcement were also discussed.

Integrated Entry Guidance for Reusable Launch Vehicle

A method for the implementation of integrated three-degree-of-freedom constrained entry guidance for reusable launch vehicle is presented. Given any feasible entry conditions, terminal area energy management interface conditions, and the reference trajectory generated onboard then, the method can generate a longitudinal guidance profile rapidly, featuring linear quadratic regular method and a proportional-integral-derivative tracking law with time-varying gains, which satisfies all the entry corridor constraints and meets the requirements with high precision. Afterwards, by utilizing special features of crossrange parameter, establishing bank-reversal corridor, and determining bank-reversals according to dynamically adjusted method, the algorithm enables the lateral entry guidance system to fly a wide range of missions and provides reliable and good performance in the presence of significant aerodynamic modeling uncertainty. Fast trajectory guidance profiles and simulations with a reusable launch vehicle model for various missions and aerodynamic uncertainties are presented to demonstrate the capacity and reliability of this method.

HYDRODYNAMIC BEHAVIOR OF AN UNDERWATER MOVING BODY AFTER WATER ENTRY

An experimental study was conducted to investigate the water entry phenomenon. A facility was designed to carry out the tests with the entry veloci- ties of around 352 m/s. Visualization, pressure ineasurement, velocity measurement and underwater impact test were performed to investigate the hydroballistic behav- ior of the underwater moving body, the underwater flow field, the supercavitation, etc.. This study shows that the motion of a high-speed underwater body is strongly three-dimensional and chaotic. Furthermore, it is found that the distribution of the trajectory deflection of the underwater projectile depends on the depth of water. It is also found by measuring the deformation on a witness plate submerged in water, that the impact energy of an underwater projectile is reduced as it penetrates deeper into water.

Control mechanism and technique of floor heave with reinforcing solid coal side and floor corner in gob-side coal entry retaining

Floor heave is the most common convergence in gob-side entry retaining.The paper analyzes the form,process and characteristics of gob-side entry retaining with the comprehensive methods of theoretical analysis,numerical simulation and the field trial.Research results present that bending and folding floor heave is the main factor in the stage of the first panel mining;squeezing and fluidity floor heave plays a great role in the stable stage of gob-side entry retaining;the combination of the former two factors affects mainly the stage of the second mining ahead;abutment pressure is a fundamental contribution to the serious floor heave of gob-side entry retaining,and sides corners of solid coal body are key part in the case of floor heave controlling of gob-side entry retaining.Floor heave of gob-side entry retaining can be significantly controlled by reinforcing sides and corners of solid coal body,and influence rules on the floor heave of gob side entry retaining of sides supporting strength and the bottom bolt orientation in solid coal side are obtained.Research results have been successfully applied in gob-side entry retaining of G20-F23070 face haulage roadway in #2 coal mine of Pingmei Group,and the field observation shows that the proposed technique is an effective way in controlling the floor heave of gob-side entry retaining.

Stability control of gob-side entry retained under the gob with close distance coal seams

In multi-seam mining,the interlayer rock strata between the upper coal seam(UCS)and the lower coal seam(LCS)appear damage and strength weakening after mining the UCS.Ground stability control of the gob-side entry retaining(GER)under the gob with close distance coal seams(CDCS)is faced with difficulties due to little attention to GER under this condition.This paper focuses on surrounding rock stability control and technical parameters design for GER under the gob with CDCS.The floor rock strata damage characteristics after mining the UCS is first evaluated and the damage factor of the interlayer rock strata below the UCS is also determined.Then,a structural mechanics model of GER surrounding rock is set up to obtain the main design parameters of the side-roadway backfill body(SBB)including the maximum and minimum SBB width calculation formula.The optimal SBB width and the water-to-cement ratio of high water quick-setting material(HWQM)to construct the SBB are determined as 1.2 m and 1.5:1.0,respectively.Finally,engineering trial tests of GER are successfully carried out at#5210 track transportation roadway of Xingwu Colliery.Research results can guide GER design under similar mining and geological conditions.

How hepatitis C virus invades hepatocytes: The mystery of viral entry

Hepatitis C virus(HCV)infection is a global health problem,with an estimated 170 million people being chronically infected.HCV cell entry is a complex multi-step process,involving several cellular factors that trigger virus uptake into the hepatocytes.The high-density lipoprotein receptor scavenger receptor class B type I,tetraspanin CD81,tight junction protein claudin-1,and occludin are the main receptors that mediate the initial step of HCV infection.In addition,the virus uses cell receptor tyrosine kinases as entry regulators,such as epidermal growth factor receptor and ephrin receptor A2.This review summarizes the current understanding about how cell surface molecules are involved in HCV attachment,internalization,and membrane fusion,and how host cell kinases regulate virus entry.The advances of the potential antiviral agents targeting this process are introduced.

Cable-truss supporting system for gob-side entry driving in deep mine and its application

In order to solve the large deformation controlling problem for surrounding rock of gob-side entry driving under common cable anchor support in deep mine, site survey, physical modeling experiment, numerical simulation and field measurement were synthetically used to analyze the deformation and failure characteristics of surrounding rock. Besides, applicability analysis, prestress field distribution characteristics of surrounding rock and the control effect on large deformation of surrounding rock were also further studied for the gob-side entry driving in deep mine using the cable-truss supporting system. The results show that, first, compared with no support and traditional bolt anchor support, roof cable-truss system can effectively restrain the initiation and propagation of tensile cracks in the roof surrounding rock and arc shear cracks in the two sides, moreover, the broken development of surrounding rock, roof separation and extrusion deformation between the two sides of the roadway are all controlled; second, a prestressed belt of trapezoidal shape is generated in the surrounding rock by the cable-truss supporting system, and the prestress field range is wide. Especially, the prestress concentration belt in the shallow surrounding rock can greatly improve the anchoring strength and deformation resisting capability of the rock stratum;third, an optimized support system of ‘‘roof and side anchor net beam, roof cable-truss supporting system and anchor cable of the narrow coal pillar" was put forward, and the support optimization design and field industrial test were conducted for the gob-side entry driving of the working face 5302 in Tangkou Mine, from which a good supporting effect was obtained.

Virus entry mediated by hepatitis B virus envelope proteins

Hepatitis B virus(HBV),a major cause of human liver disease worldwide,encodes three envelope proteins needed for the attachment and entry of the virus into susceptible host cells.A second virus,hepatitis delta virus,which is known to enhance liver disease in HBV infected patients,diverts the same HBV envelope proteins to achieve its own assembly and infection.In the lab,lentiviral vectors based on human immunodeficiency virus type 1 can be assembled using the HBV envelope proteins,and will similarly infect susceptible cells.This article provides a partial review and some personal reflections of how these three viruses infect and of how recipient cells become susceptible,along with some consideration of questions that remain to be answered.

Thermochemical ablation of spherical cone during re-entry

Presents the use of the similar transform and potential theory for calculation of the bypass flow factor and pressure gradient and the analysis of the influence of bypass flow factor and pressure gradient on heat transfer is analyzed, and the distribution of nose cone ablation obtained by combining the controlling equations of boundary layer, the compatible relation of interface and the heat conduction of interior.