Analysis on Technology of High-Frequency Vibratory Stress Relief

Abstract-In the paper, a new kind of Vibratory Stress Relief (VSR), which is called high-frequency VSR, is put forward. Firstly, the traditional VSR or low-frequency VSR is introduced, including its method and mechanism. Then a new kind of VSR experimental equipment, which exciting frequency is more than 1kHz, is suggested. The experimental results show that it could decrease the residual stress efficiently. Metallographic is also analyzed, which gives a fancy phenomenon: the number of dislocations in material decreases after high-frequency VSR, which seems that the material recovers its original and non-stress state; on the contrary, the number of dislocations in material increases after traditional VSR. Finally, the underlying prospect of new concept "high-frequency VSR" is estimated. The advanced concept will take the significant effect on the wide application of VSR and energy conservation

BMAL1 but not CLOCK is associated with monochromatic green light-induced circadian rhythm of melatonin in chick pinealocytes

The avian pineal gland, an independent circadian oscillator, receives external photic cues and translates them for the rhythmical synthesis of melatonin. Our previous study found that monochromatic green light could increase the secretion of melatonin and expression of CLOCK and BMAL1 in chick pinealocytes. This study further investigated the role of BMAL1 and CLOCK in monochromatic green light-induced melatonin secretion in chick pinealocytes using siRNAs interference and overexpression techniques. The results showed that si-BMAL1 destroyed the circadian rhythms of AANAT and melatonin, along with the disruption of the expression of all the seven clock genes, except CRY1. Furthermore, overexpression of BMAL1 also disturbed the circadian rhythms of AANAT and melatonin, in addition to causing arrhythmic expression of BMAL1 and CRY1/2, but had no effect on the circadian rhythms of CLOCK, BMAL2 and PER2/3. The knockdown or overexpression of CLOCK had no impact on the circadian rhythms of AANAT, melatonin, BMAL1 and PER2, but it significantly deregulated the circadian rhythms of CLOCK, BMAL2, CRY1/2 and PER3. These results suggested that BMAL1 rather than CLOCK plays a critical role in the regulation of monochromatic green light-induced melatonin rhythm synthesis in chicken pinealocytes. Moreover, both knockdown and overexpression of BMAL1 could change the expression levels of CRY2, it indicated CRY2 may be involved in the BMAL1 pathway by modulating the circadian rhythms of AANAT and melatonin

ECA-TFUnet: A U-shaped CNN-Transformer network with efficient channel attention for organ segmentation in anatomical sectional images of canines

Automated organ segmentation in anatomical sectional images of canines is crucial for clinical applications and the study of sectional anatomy. The manual delineation of organ boundaries by experts is a time-consuming and laborious task. However, semi-automatic segmentation methods have shown low segmentation accuracy. Deep learning-based CNN models lack the ability to establish long-range dependencies, leading to limited segmentation performance. Although Transformer-based models excel at establishing long-range dependencies, they face a limitation in capturing local detail information. To address these challenges, we propose a novel ECA-TFUnet model for organ segmentation in anatomical sectional images of canines. ECA-TFUnet model is a U-shaped CNN-Transformer network with Efficient Channel Attention, which fully combines the strengths of the Unet network and Transformer block. Specifically, The U-Net network is excellent at capturing detailed local information. The Transformer block is equipped in the first skip connection layer of the Unet network to effectively learn the global dependencies of different regions, which improves the representation ability of the model. Additionally, the Efficient Channel Attention Block is introduced to the Unet network to focus on more important channel information, further improving the robustness of the model. Furthermore, the mixed loss strategy is incorporated to alleviate the problem of class imbalance. Experimental results showed that the ECA-TFUnet model yielded 92.63% IoU, outperforming 11 state-of-the-art methods. To comprehensively evaluate the model performance, we also conducted experiments on a public dataset, which achieved 87.93% IoU, still superior to 11 state-of-the-art methods. Finally, we explored the use of a transfer learning strategy to provide good initialization parameters for the ECA-TFUnet model. We demonstrated that the ECA-TFUnet model exhibits superior segmentation performance on anatomical sectional images of canines, which has the potential for application in medical clinical diagnosis

Antibody Evasion by SARS-CoV-2 Omicron Subvariants BA2121, BA4 and BA5

SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged notably to become dominant in the United States and South Africa, respectively1,2. These new subvariants carrying further mutations in their spike proteins raise concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of COVID-19 vaccines and therapeutic monoclonals. We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called class 2 and 3 regions of the receptor-binding domain3. The F486V mutation found in BA.4/5 facilitates escape from certain class 1 and 2 antibodies but compromises the spike affinity for the viral receptor. The R493Q reversion mutation, however, restores receptor affinity and consequently the fitness of BA.4/5. Among therapeutic antibodies authorized for clinical use, only bebtelovimab retains full potency against both BA.2.12.1 and BA.4/5. The Omicron lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies

Phase 1 Safety and Immunogenicity Evaluation of ADMVA, a Multigenic, Modified Vaccinia Ankara-HIV-1 B'/C Candidate Vaccine

in a modified vaccinia Ankara viral vector. Sequences were derived from a prevalent circulating HIV-1 recombinant form in Yunnan, China, an area of high HIV incidence. The objective was to evaluate the safety and immunogenicity of ADMVA in human volunteers.. Two volunteers mounted antibodies that were able to neutralize clade-matched viruses.ADMVA was well-tolerated and elicited durable humoral and cellular immune responses

SARS-CoV-2 infection causes dopaminergic neuron senescence

COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.</p

SARS-CoV-2 infection causes dopaminergic neuron senescence

COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.</p

Phase 1 Safety and Immunogenicity Evaluation of ADVAX, a Multigenic, DNA-Based Clade C/B' HIV-1 Candidate Vaccine

BACKGROUND: We conducted a Phase I dose escalation trial of ADVAX, a DNA-based candidate HIV-1 vaccine expressing Clade C/B' env, gag, pol, nef, and tat genes. Sequences were derived from a prevalent circulating recombinant form in Yunnan, China, an area of high HIV-1 incidence. The objective was to evaluate the safety and immunogenicity of ADVAX in human volunteers. METHODOLOGY/PRINCIPAL FINDINGS: ADVAX or placebo was administered intramuscularly at months 0, 1 and 3 to 45 healthy volunteers not at high risk for HIV-1. Three dosage levels [0.2 mg (low), 1.0 mg (mid), and 4.0 mg (high)] were tested. Twelve volunteers in each dosage group were assigned to receive ADVAX and three to receive placebo in a double-blind design. Subjects were followed for local and systemic reactogenicity, adverse events, and clinical laboratory parameters. Study follow up was 18 months. Humoral immunogenicity was evaluated by anti-gp120 binding ELISA. Cellular immunogenicity was assessed by a validated IFNgamma ELISpot assay and intracellular cytokine staining. ADVAX was safe and well-tolerated, with no vaccine-related serious adverse events. Local and systemic reactogenicity events were reported by 64% and 42% of vaccine recipients, respectively. The majority of events were mild. The IFNgamma ELISpot response rates to any HIV antigen were 0/9 (0%) in the placebo group, 3/12 (25%) in the low-dosage group, 4/12 (33%) in the mid-dosage group, and 2/12 (17%) in the high-dosage group. Overall, responses were generally transient and occurred to each gene product, although volunteers responded to single antigens only. Binding antibodies to gp120 were not detected in any volunteers, and HIV seroconversion did not occur. CONCLUSIONS/SIGNIFICANCE: ADVAX delivered intramuscularly is safe, well-tolerated, and elicits modest but transient cellular immune responses. TRIAL REGISTRATION: Clinicaltrials.gov NCT00249106.published_or_final_versio

In Vivo Electroporation Enhances the Immunogenicity of an HIV-1 DNA Vaccine Candidate in Healthy Volunteers

DNA-based vaccines have been safe but weakly immunogenic in humans to date.We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP) in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines.This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate.ClinicalTrials.gov NCT00545987

High-amylose starch-based gel as green adhesive for plywood:Adhesive property, water-resistance, and flame-retardancy

The escalating demand for environmentally sustainable and cost-effective adhesives in the wood processing and manufacturing sector has prompted exploration into innovative solutions. This study introduces a novel gel adhesive composed of chemically unmodified high-amylose starch (G70, with 68 % amylose content) with a minimal proportion of urea-formaldehyde (UF) (UF/starch = 1:10, w/w). This G70/UF gel demonstrates remarkable adhesive capabilities for wooden boards under both dry conditions (with a shear stress of 4.13 ± 0.12 MPa) and wet conditions (with a shear strength of 0.93 ± 0.07 MPa after 2 h of water soaking). The study unveils that the elevated amylose content in the starch, coupled with a meticulously controlled isothermal process during bonding, is crucial for these enhancements. Specifically, the robust cohesion of amylose chains expedites phase separation between starch and UF, while the isothermal process facilitates the migration and enrichment of UF molecules at the gel-board and gel-air interfaces. Lacking these mechanisms, conventional amylopectin-rich starch/UF gels (27 % amylose content) show minimal improvement. Moreover, the G70/UF gel showcases exceptional fire retardancy. In all, the G70/UF gel presents a promising alternative for plywood production, reducing reliance on unhealthy UF resin while offering satisfactory bonding resistance in diverse conditions and superior flame retardancy.</p