8 research outputs found
Investigation of Sandstone Mesostructure Damage Caused by Freeze-Thaw Cycles via CT Image Enhancement Technology
The mesostructures of rocks determine their macromechanical properties. These rock mesostructures may be altered by the freeze-thaw cycles in cold regions. In this regard, this paper proposes a quantitative evaluation method based on computed tomography (CT) scanning technology for investigating the mesostructure and damage characteristics of sandstone subjected to freeze-thaw conditions. CT scan images of two sandstones with different grain sizes were obtained after 0, 20, 40, 60, 80, and 100 freeze-thaw cycles, using a high-precision CT scanner. Based on the microphysical information contained in these CT images, pseudo-color-enhancement of the CT images of rocks subjected to freeze-thaw cycles was realized. The use of such a pseudo-color-enhancement technique can improve the resolution of CT images. Thus, particle detachment, crack initiation, crack propagation, and increased porosity due to the volumetric expansion of water inside the rock could be detected and clearly observed. Furthermore, a numerical expression for the mesostructure and damage information contained in the pseudo-color-enhanced images is presented herein; this serves as a convenient method for quantitative analyses of sandstone damage under freeze-thaw cycles. An analysis of the pseudo-color-enhanced images shows that, under freeze-thaw cycles, damage propagation in sandstone originates from existing damage or defect sites. After the stages of crack (pore) formation, penetration, and propagation, the freeze-thaw cycle-induced damage increases gradually, while the effective bearing area of the rock decreases continuously. Herein, a schematic of a conceptual model for the freeze-thaw cycle-induced deterioration in sandstone mesostructures is presented. Damage propagation models for sandstones with two different grain sizes subjected to freeze-thaw cycles were also developed. Based on the damage mechanics theory, a damage variable expressed in terms of the pore area was defined. Moreover, the relationship between this damage variable and the freeze-thaw cycles was established
Long-Term Impact of Immunosuppressants at Therapeutic Doses on Male Reproductive System in Unilateral Nephrectomized Rats: A Comparative Study
Cyclosporine, tacrolimus, and sirolimus are commonly used in renal transplant recipients to prevent rejection. However, information for comparative effects of these agents on the male productive system is extremely limited and controversial. In a physiologically and clinically relevant rat model of unilateral nephrectomy, we demonstrated that long-term oral administration of both cyclosporine and sirolimus at doses equivalent to the therapeutic levels used for postrenal transplant patients significantly affects testicular development and the hypothalamic-pituitary-gonadal axis accompanied by profound histological changes of testicular structures on both light and electron microscopic examinations. Spermatogenesis was also severely impaired as indicated by low total sperm counts along with reduction of sperm motility and increase in sperm abnormality after treatment with these agents, which may lead to male infertility. On the other hand, treatment with therapeutic dose of tacrolimus only induced mild reduction of sperm count without histological evidence of testicular injury. The current study clearly demonstrates that commonly used immunosuppressants have various impacts on male reproductive system even at therapeutic levels. Our data provide useful information for the assessment of male infertility in renal transplant recipients who wish to father children. Clinical trials to address these issues should be urged
Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2
10.1038/s41598-023-49231-wSCIENTIFIC REPORTS13
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Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2
Acknowledgements: This work was supported by the Biomedical Research Council (BMRC), A*CRUSE (Vaccine monitoring project), the A*ccelerate GAP-funded project (ACCL/19-GAP064-R20H-H) from Agency of Science, Technology and Research (A*STAR), Singapore National Medical Research Council COVID-19 Research Fund (COVID19RF-001; COVID19RF-007; COVID19RF-0008; COVID19RF-060) and A*STAR COVID-19 Research funding (H/20/04/g1/006). This study is funded by the Singapore National Medical Research Council (R-571-000-081-213, R-711-000-058-598), Ministry of Health (R-571-000-093-114), National University of Singapore (R-571-000-081-213), and the Singapore-HUJ Alliance for Research and Enterprise (R-571-002-012-592). We thank Protein Production Platform of Nanyang Technological University for their help in making the nucleocapsid expression constructs and small-scale protein expression tests. We thank Assoc Prof. Tan Yee Joo, Department of Microbiology and Immunology, Yong Loo Lin, School of Medicine, National University of Singapore (NUS) for the ACE2 stably expressing CHO cells and plasmid encoding SARS-CoV-2 S protein for the pseudotyped lentiviral production. We thank Ms. Lang Si Min and Ms. Tan Siang Ling Isabelle for helping with the performance of experiments.AbstractThe scale and duration of neutralizing antibody responses targeting SARS-CoV-2 viral variants represents a critically important serological parameter that predicts protective immunity for COVID-19. In this study, we describe the development and employment of a new functional assay that measures neutralizing antibodies for SARS-CoV-2 and present longitudinal data illustrating the impact of age, sex and comorbidities on the kinetics and strength of vaccine-induced antibody responses for key variants in an Asian volunteer cohort. We also present an accurate quantitation of serological responses for SARS-CoV-2 that exploits a unique set of in-house, recombinant human monoclonal antibodies targeting the viral Spike and nucleocapsid proteins and demonstrate a reduction in neutralizing antibody titres across all groups 6 months post-vaccination. We also observe a marked reduction in the serological binding activity and neutralizing responses targeting recently newly emerged Omicron variants including XBB 1.5 and highlight a significant increase in cross-protective neutralizing antibody responses following a third dose (boost) of vaccine. These data illustrate how key virological factors such as immune escape mutations combined with host demographic factors such as age and sex of the vaccinated individual influence the strength and duration of cross-protective serological immunity for COVID-19.</jats:p
Lower vaccine-acquired immunity in the elderly population following two-dose BNT162b2 vaccination is alleviated by a third vaccine dose
Understanding the impact of age on vaccinations is essential for the design and delivery of vaccines against SARS-CoV-2. Here, we present findings from a comprehensive analysis of multiple compartments of the memory immune response in 312 individuals vaccinated with the BNT162b2 SARS-CoV-2 mRNA vaccine. Two vaccine doses induce high antibody and T cell responses in most individuals. However, antibody recognition of the Spike protein of the Delta and Omicron variants is less efficient than that of the ancestral Wuhan strain. Age-stratified analyses identify a group of low antibody responders where individuals ≥60 years are overrepresented. Waning of the antibody and cellular responses is observed in 30% of the vaccinees after 6 months. However, age does not influence the waning of these responses. Taken together, while individuals ≥60 years old take longer to acquire vaccine-induced immunity, they develop more sustained acquired immunity at 6 months post-vaccination. A third dose strongly boosts the low antibody responses in the older individuals against the ancestral Wuhan strain, Delta and Omicron variants