Analysis of spike protein variants evolved in a novel in vivo long-term replication model for SARS-CoV-2

IntroductionThe spectrum of SARS-CoV-2 mutations have increased over time, resulting in the emergence of several variants of concern. Persistent infection is assumed to be involved in the evolution of the variants. Calu-3 human lung cancer cells persistently grow without apoptosis and release low virus titers after infection.MethodsWe established a novel in vivo long-term replication model using xenografts of Calu-3 human lung cancer cells in immunodeficient mice. Virus replication in the tumor was monitored for 30 days and occurrence of mutations in the viral genome was determined by whole-genome deep sequencing. Viral isolates with mutations were selected after plaque forming assays and their properties were determined in cells and in K18-hACE2 mice.ResultsAfter infection with parental SARS-CoV-2, viruses were found in the tumor tissues for up to 30 days and acquired various mutations, predominantly in the spike (S) protein, some of which increased while others fluctuated for 30 days. Three viral isolates with different combination of mutations produced higher virus titers than the parental virus in Calu-3 cells without cytopathic effects. In K18-hACE2 mice, the variants were less lethal than the parental virus. Infection with each variant induced production of cross-reactive antibodies to the receptor binding domain of parental SARS-CoV-2 S protein and provided protective immunity against subsequent challenge with parental virus.DiscussionThese results suggest that most of the SARS-CoV-2 variants acquired mutations promoting host adaptation in the Calu-3 xenograft mice. This model can be used in the future to further study SARS-CoV-2 variants upon long-term replication in vivo

Positional Reproducibility and Effects of a Rectal Balloon in Prostate Cancer Radiotherapy

Despite the increasing use of the rectal balloon in prostate cancer radiotherapy, many issues still remain to be verified objectively including its positional reproducibility and relevance to treatment morbidity. We have developed a custom rectal balloon that has a scale indicating the depth of insertion and dilates symmetrically ensuring positional reproducibility. Fifty patients with prostate cancer treated by definitive 3D-conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) with rectal balloon were analyzed. Each of first five patients undergone computed tomography (CT) three times with a rectal balloon. The positional reproducibility was tested by Intraclass Correlation Coefficient (ICC) from the CT-to-CT fusion images. Planning variables and clinical acute toxicities were compared between when or not applying balloon. An ICC of greater than 0.9 in all directions revealed an excellent reproducibility of the balloon. Rectal balloon improved considerably the mean dose and V45Gy-V65Gy in plan comparison, and especially in 3D-CRT the rectal volume exposed to more than 60 Gy dropped from 41.3% to 19.5%. Clinically, the balloon lowered acute toxicity, which was lowest when both the balloon and IMRT were applied simultaneously. The rectal balloon carries excellent reproducibility and reduces acute toxicity in 3D-CRT and IMRT for prostate cancer

Address-free contention in wireless access networks with common control channel for throughput improvement

In wireless local area network (WLAN) with common control channel (CCC), where the spectrum bandwidth is divided into two separate channels for access control and data transmission, concurrent transmissions of control and data frames can improve the spectrum efficiency by pipelining data transmissions. However, the state-of-the-art MAC schemes cannot fully exploit the channel separation due to large control overhead and receiver contention problem, where the former causes bandwidth erosion reducing the data transmission rate and the latter prevents the pipelining when two consecutive transmissions involve a common node as the receiver. In this paper, we focus on the two problems, and develop a novel CCC-based MAC scheme with address-free contention resolution for wireless access networks. Through both analysis and simulations, we show that the proposed scheme minimizes the control overhead and significantly improves the spectrum efficiency: It achieves as twice throughput as the conventional CCC-based MAC and 30% average performance gain over IEEE 802.11 MAC.close0

Automatic compensation enhances the orientation perception in chronic astigmatism

© 2022. The Author(s).Astigmatism is a prevalent optical problem in which two or more focal points blur the retinal image at a particular meridian. Although many features of astigmatic vision, including orientation perception, are impaired at the retinal image level, the visual system appears to partly restore perceptual impairment after an extended period of astigmatism. However, the mechanism of orientation perception restoration in chronic astigmatism has not yet been clarified. We investigated the notable reduction of perceptual error in chronic astigmatism by comparing the orientation perception of a chronic astigmatism group with the perception of a normal-vision group, in which astigmatism was transiently induced. We found that orientation perception in the chronic group was more accurate than in the normal vision group. Interestingly, the reduction of perceptual errors was automatic; it remained even after the optical refractive errors were fully corrected, and the orientation perception was much more stable across different orientations, despite the uneven noise levels of the retinal images across meridians. We provide here a mechanistic explanation for how the compensation of astigmatic orientation perception occurred, using neural adaptation to the biased distribution of orientations.11Nsciescopu

Resonant frequency variations in a piezoelectric microcantilever sensor under varying operational conditions

The dependence of the resonant frequency of a piezoelectric microcantilever sensor (PEMS) on electrostatic discharge (ESD), oscillating voltage, dc bias and time was measured from its electrical response. Linear and nonlinear characteristics of the PEMS were analyzed using a lumped parameter model. In particular, the Duffing model-a nonlinear phenomenological model-was adopted to analyze the effects of varying oscillating voltage. The results showed that the ESD can produce a variation in resonant frequency, but can be prevented by earth grounding. In addition, an increase in the oscillating voltage led to a decrease in the resonant frequency owing to the nonlinear spring effect. The resonant frequency exhibited hysteretic behavior with varying dc bias and increased with time. The resonant frequency changed by approximately 18.5 kHz when the oscillating voltage was increased from 0.05 V to 1 V, approximately 9 kHz when the dc bias voltage was increased from 0 V to 20 V and approximately 3.062 kHz over 12 h owing to time drift. The time drift over a period of 30 min remarkably reduced from approximately 0.09% to 0.0049% after a stabilizing time period of approximately 6 h.X1154sciescopu

Induced astigmatism biases the orientation information represented in multivariate electroencephalogram activities

© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.A small physical change in the eye influences the entire neural information process along the visual pathway, causing perceptual errors and behavioral changes. Astigmatism, a refractive error in which visual images do not evenly focus on the retina, modulates visual perception, and the accompanying neural processes in the brain. However, studies on the neural representation of visual stimuli in astigmatism are scarce. We investigated the relationship between retinal input distortions and neural bias in astigmatism and how modulated neural information causes a perceptual error. We induced astigmatism by placing a cylindrical lens on the dominant eye of human participants, while they reported the orientations of the presented Gabor patches. The simultaneously recorded electroencephalogram activity revealed that stimulus orientation information estimated from the multivariate electroencephalogram activity was biased away from the neural representation of the astigmatic axis and predictive of behavioral bias. The representational neural dynamics underlying the perceptual error revealed the temporal state transition; it was transiently dynamic and unstable (approximately 350 ms from stimulus onset) that soon stabilized. The biased stimulus orientation information represented by the spatially distributed electroencephalogram activity mediated the distorted retinal images and biased orientation perception in induced astigmatism.11Nsciescopu

Senescence-Induced Serotonin Biosynthesis and Its Role in Delaying Senescence in Rice Leaves1[C][W][OA]

Serotonin, which is well known as a pineal hormone in mammals, plays a key role in conditions such as mood, eating disorders, and alcoholism. In plants, although serotonin has been suggested to be involved in several physiological roles, including flowering, morphogenesis, and adaptation to environmental changes, its regulation and functional roles are as yet not characterized at the molecular level. In this study, we found that serotonin is greatly accumulated in rice (Oryza sativa) leaves undergoing senescence induced by either nutrient deprivation or detachment, and its synthesis is closely coupled with transcriptional and enzymatic induction of the tryptophan biosynthetic genes as well as tryptophan decarboxylase (TDC). Transgenic rice plants that overexpressed TDC accumulated higher levels of serotonin than the wild type and showed delayed senescence of rice leaves. However, transgenic rice plants, in which expression of TDC was suppressed through an RNA interference (RNAi) system, produced less serotonin and senesced faster than the wild type, suggesting that serotonin is involved in attenuating leaf senescence. The senescence-retarding activity of serotonin is associated with its high antioxidant activity compared to either tryptophan or chlorogenic acid. Results of TDC overexpression and TDC RNAi plants suggest that TDC plays a rate-limiting role for serotonin accumulation, but the synthesis of serotonin depends on an absolute amount of tryptophan accumulation by the coordinate induction of the tryptophan biosynthetic genes. In addition, immunolocalization analysis revealed that serotonin was abundant in the vascular parenchyma cells, including companion cells and xylem-parenchyma cells, suggestive of its involvement in maintaining the cellular integrity of these cells for facilitating efficient nutrient recycling from senescing leaves to sink tissues during senescence