Addressing preferred orientation in single-particle cryo-EM through AI-generated auxiliary particles

The single-particle cryo-EM field faces the persistent challenge of preferred orientation, lacking general computational solutions. We introduce cryoPROS, an AI-based approach designed to address the above issue. By generating the auxiliary particles with a conditional deep generative model, cryoPROS addresses the intrinsic bias in orientation estimation for the observed particles. We effectively employed cryoPROS in the cryo-EM single particle analysis of the hemagglutinin trimer, showing the ability to restore the near-atomic resolution structure on non-tilt data. Moreover, the enhanced version named cryoPROS-MP significantly improves the resolution of the membrane protein NaX using the no-tilted data that contains the effects of micelles. Compared to the classical approaches, cryoPROS does not need special experimental or image acquisition techniques, providing a purely computational yet effective solution for the preferred orientation problem. Finally, we conduct extensive experiments that establish the low risk of model bias and the high robustness of cryoPROS

Zanthoxylum bungeanum seed oil inhibits tumorigenesis of human melanoma A375 by regulating CDC25A/CyclinB1/CDK1 signaling pathways in vitro and in vivo

Background:Zanthoxylum bungeanum seed oil (ZBSO) is extracted from the seeds of the traditional Chinese medicine Z. bungeanum Maxim, which has been shown to have anti-melanoma effects. However, the specific mechanisms are not illustrated adequately.Aims: To further investigate the mechanism by which ZBSO inhibits melanoma and to provide scientific evidence to support ZBSO as a potential melanoma therapeutic candidate.Methods: CCK-8 assays were used to detect the function of ZBSO on A375 cells. Based on transcriptomics analyses, Western blot analysis was applied to determine whether an association existed in ZBSO with the CDC25A/CyclinB1/CDK1 signaling pathway. In addition, RT-qPCR and immunohistochemistry analysis validated that ZBSO has the anti-melanoma effect in a nude mouse xenograft model of human melanoma. Then, 16S rRNA sequencing was used to detect the regulation of gut microbes.Results: Cellular assays revealed that ZBSO could inhibit A375 cell viability by regulating the cell cycle pathway. Further studies presented that ZBSO could constrain CDC25A/CyclinB1/CDK1 signaling pathway in vitro and in vivo models of melanoma. ZBSO did not produce toxicity in mice, and significantly reduced tumor volume in xenotransplants of A375 cells. Genome analysis indicated that ZBSO successfully altered specific gut microbes.Conclusion: ZBSO inhibited the growth of A375 cells by regulating CDC25A/cyclinB1/CDK1 signaling pathway both in vitro and in vivo, suggesting that ZBSO may be a novel potential therapeutic agent

In Vivo Disruption of TGF-β Signaling by Smad7 in Airway Epithelium Alleviates Allergic Asthma but Aggravates Lung Carcinogenesis in Mouse

BACKGROUND: TGF-beta has been postulated to play an important role in the maintenance of epithelial homeostasis and the development of epithelium-derived cancers. However, most of previous studies are mainly focused on the function of TGF-beta in immune cells to the development of allergic asthma and how TGF-beta signaling in airway epithelium itself in allergic inflammation is largely unknown. Furthermore, the in vivo TGF-beta function specifically in the airway epithelium during lung cancer development has been largely elusive. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the in vivo contribution of TGF-beta signaling in lung epithelium to the development of allergic disease and lung cancer, we generated a transgenic mouse model with Smad7, an intracellular inhibitor of TGF-beta signaling, constitutively expressed in mouse airway Clara cells using a mouse CC10 promoter. The mice were subjected to the development of OVA-induced allergic asthma and urethane-induced lung cancer. The Smad7 transgenic animals significantly protected from OVA-induced asthma, with reduced airway inflammation, airway mucus production, extracellular matrix deposition, and production of OVA-specific IgE. Further analysis of cytokine profiles in lung homogenates revealed that the Th2 cytokines including IL-4, IL-5 and IL-13, as well as other cytokines including IL-17, IL-1, IL-6, IP10, G-CSF, and GM-CSF were significantly reduced in the transgenic mice upon OVA induction. In contrast, the Smad7 transgenic animals had an increased incidence of lung carcinogenesis when subjected to urethane treatment. CONCLUSION/SIGNIFICANCE: These studies, therefore, demonstrate for the first time the in vivo function of TGF-beta signaling specifically in airway epithelium during the development of allergic asthma and lung cancer

Multi-bit quantum random number generation by measuring positions of arrival photons

We report upon the realization of a novel multi-bit optical quantum random number generator by continuously measuring the arrival positions of photon emitted from a LED using MCP-based WSA photon counting imaging detector. A spatial encoding method is proposed to extract multi-bits random number from the position coordinates of each detected photon. The randomness of bits sequence relies on the intrinsic randomness of the quantum physical processes of photonic emission and subsequent photoelectric conversion. A prototype has been built and the random bit generation rate could reach 8 Mbit/s, with random bit generation efficiency of 16 bits per detected photon. FPGA implementation of Huffman coding is proposed to reduce the bias of raw extracted random bits. The random numbers passed all tests for physical random number generator. (C) 2014 AIP Publishing LLC

Photon-Counting Underwater Optical Wireless Communication for Reliable Video Transmission Using Joint Source-Channel Coding Based on Distributed Compressive Sensing

To achieve long-distance underwater optical wireless communication, a single photon detector with single photon limit sensitivity is used to detect the optical signal at the receiver. The communication signal is extracted from the discrete single photon pulses output from the detector. Due to fluctuation of photon flux and quantum efficiency of photon detection, long-distance underwater optical wireless communication has the characteristics that the link is easily interrupted, the bit error rate is high, and the burst error is large. To achieve reliable video transmission, a joint source-channel coding scheme based on residual distributed compressive video sensing is proposed for the underwater photon counting communication system. Signal extraction from single photon pulses, data frame and data verification are specifically designed. This scheme greatly reduces the amount of data at the transmitter, transfers the computational complexity to the decoder in receiver, and enhances anti-channel error ability. The experimental results show that, when the baud rate was 100 kbps and the average number of photon pulses per bit was 20, the bit error rate (BER) was 0.0421 and video frame could still be restored clearly

Measurement Matrix Construction for Large-area Single Photon Compressive Imaging

We have developed a single photon compressive imaging system based on single photon counting technology and compressed sensing theory, using a photomultiplier tube (PMT) photon counting head as the bucket detector. This system can realize ultra-weak light imaging with the imaging area up to the entire digital micromirror device (DMD) working region. The measurement matrix in this system is required to be binary due to the two working states of the micromirror corresponding to two controlled elements. And it has a great impact on the performance of the imaging system, because it involves modulation of the optical signal and image reconstruction. Three kinds of binary matrix including sparse binary random matrix, m sequence matrix and true random number matrix are constructed. The properties of these matrices are analyzed theoretically with the uncertainty principle. The parameters of measurement matrix including sparsity ratio, compressive sampling ratio and reconstruction time are verified in the experimental system. The experimental results show that, the increase of sparsity ratio and compressive sampling ratio can improve the reconstruction quality. However, when the increase is up to a certain value, the reconstruction quality tends to be saturated. Compared to the other two types of measurement matrices, the m sequence matrix has better performance in image reconstruction

Quantitative characterization of aggregates and their chemical constituents in terms of acid and alkaline indicators

The acidity and alkalinity of aggregates greatly affect the stability, demulsification rate, and road performance of asphalt mixtures. To study the effect of acidity and alkalinity and chemical composition of aggregates, five aggregates, namely limestone (S1, S2, S3, S4) and basalt (X), were studied. The pH and alkalinity values of aggregates and their main chemical compositions (MgO, Al2O3, CaO, Fe2O3, and SiO2) were tested. The pH/alkalinity measured values and pH/alkalinity composite values of the aggregates were analyzed using grey correlation and principal component analyses. The findings indicated a strong correlation between the composite and measured values for aggregate acidity and alkalinity indexes (pH: 0.9105, alkalinity: 0.9241). Additionally, the principal component analysis demonstrated that the composite values were in good agreement with the measured values (pH: R2 = 0.746, alkalinity: R2 = 0.992), which corroborated the grey correlation and regression model results, confirming significant correlations. This result indicates that the pH/alkaline index of the chemical constituents of the aggregate can be used to characterize the pH/alkaline index of the aggregate. The relationship model between aggregate and their chemical constituent’s acid and alkaline indexes can provide a theoretical reference for the in-depth study of the application of aggregate acid and alkaline in road engineering

Changes in Expression in BMP2 and Two Closely Related Genes in Guinea Pig Retinal Pigment Epithelium during Induction and Recovery from Myopia.

PURPOSE: We previously reported differential gene expression of the bone morphogenetic protein 2 (Bmp2) in guinea pig retinal pigment epithelium (RPE) after 1 day of hyperopic defocus, imposed with a negative contact lens (CLs). The study reported here sought to obtain insights into the temporal profiles of gene expression changes in Bmp2, as well as those of two closely related genes, the inhibitor of DNA binding 3 (Id3) and Noggin (Nog), both during myopia induction and when the CL treatment was terminated to allow recovery from induced myopia. METHODS: To induce myopia, 2-week-old pigmented guinea pigs (New Zealand strain, n = 8) wore monocular -10 diopter (D) rigid gas-permeable (RGP) CLs for one week, while the other eye served as a control. Ocular measurements were made at baseline, 3 days, and 7 days after the initiation of CL wear, with treatment then being terminated and additional measurements being made after a further 3 days, 1 week, and 2 weeks. Spherical equivalent refractive errors (SERs), axial length (AL), choroidal thickness (ChT), and scleral thickness (ScT) data were collected using retinoscopy, optical biometry (Lenstar), and spectral domain optical coherence tomography (SD-OCT), respectively. RPE samples were collected from both eyes of the guinea pigs after either 1 day or 1 week of CL wear or 1 day or 2 weeks after its termination, and RNA was subsequently isolated and subjected to quantitative real-time PCR (qRT-PCR) analyses, targeting the Bmp2, Id3, and Nog genes. RESULTS: Mean interocular differences (treated-control) in AL and SER were significantly different from baseline after 3 and 7 days of CL wear, consistent with induced myopia (p < 0.001 for all cases). Termination of CL wear resulted in the normalization (i.e., recovery) of the ALs and SERs of the treated eyes within 7 days, and the earlier significant ChT thinning with CL wear (p = 0004, day 7) was replaced by rapid thickening, which remained significant on day 7 (p = 0.009) but had normalized by day 14. The ChT changes were much smaller in magnitude than the AL changes in both phases. Interocular differences in the ScT showed no significant changes. The Bmp2 and Id3 genes were both significantly downregulated with CL wear, after 1 day (p = 0.012 and 0.016) and 7 days (p = 0.002 and 0.005), while Bmp2 gene expression increased and Nog gene expression decreased after the termination of CL wear, albeit transiently, which was significant on 1 day (p = 0.004 and 0.04) but not 2 weeks later. No change in Id3 gene expression was observed over the latter period. Conclusions: The above patterns of myopia induction and recovery validate this negative RGP-CL model as an alternative to traditional spectacle lens models for guinea pigs. The defocus-driven, sign-dependent changes in the expression of the Bmp2 gene in guinea pig RPE are consistent with observations in chicks and demonstrate the important role of BMP2 in eye growth regulation

The resolution estimation of wedge and strip anodes

A new resolution estimation method for wedge and strip anode based on the single photon imaging configuration is provided. The limiting resolution estimation equation is deduced theoretically according to the threshold principle. The relation between the charge cloud and the covered electrodes is discussed, and the equivalent diameter number is calculated. The resolution equation for the position deviation amplitude or FWHM is provided if noise exists. The relation between the position deviation amplitude and the total charge deviation amplitudes is discussed. The constancy of the position deviation amplitudes versus positions is provided. The results calculated from these equations are discussed. According to the equations, it is indicated that the spatial resolution is affected by the detection system configuration and noise. These conclusions may be useful for the designing and performance improvement of future photon imagers. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4729117

Ghosting phenomena in single photon counting imagers with Vernier anode

We provide the ghosting theory of two-dimensional Vernier anode based imagers. The single photon counting detection system based on Vernier anode is constructed. The ghosting, which occurs during the decoding of two-dimensional Vernier anode, and its possible solutions are described in detail. On the basis of the discussion of the decoding algorithm, the ghosting theoretical model is established. Phase conditions on which imaging ghosting can be avoided and the probability distribution function are proposed; the root causes of ghosting of two-dimensional Vernier anode are also discussed. (C) 2011 American Institute of Physics. [doi:10.1063/1.3544018