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Thomasen posted an update 9 months ago
In addition, we showed that an imbalance in binding of HSP47-R222S to unfolded type I collagen chains in a gelatin sepharose pulldown assay results in increased binding of other chaperones and modifying enzymes. The elevated expression and binding of this molecular ensemble to type I procollagen suggests a compensatory mechanism for the aberrant binding of HSP47-R222S, eventually leading to overmodification of type I procollagen chains. Together, these results illustrate the importance of HSP47 for proper posttranslational modification and provide insights into the molecular pathomechanisms of the p.(R222S) alteration in HSP47, which leads to a severe OI phenotype.Biofilm formation protects bacteria from antibiotics. Very little is known about the response of biofilm-dwelling bacteria to antibiotics at the single cell level. Here, we developed a cell-tracking approach to investigate how antibiotics affect structure and dynamics of colonies formed by the human pathogen Neisseria gonorrhoeae. Antibiotics targeting different cellular functions enlarge the cell volumes and modulate within-colony motility. Focusing on azithromycin and ceftriaxone, we identify changes in type 4 pilus (T4P) mediated cell-to-cell attraction as the molecular mechanism for different effects on motility. By using strongly attractive mutant strains, we reveal that the survivability under ceftriaxone treatment depends on motility. Combining our results, we find that sequential treatment with azithromycin and ceftriaxone is synergistic. Taken together, we demonstrate that antibiotics modulate T4P-mediated attractions and hence cell motility and colony fluidity.In this study, graphene oxide sheets with different oxidation degrees were reduced by ferrous ion for coating FeOOH nano particles on reduced graphene oxide (rGO) matrix to synthesize FeOOH/rGO composites. The effect of the degree of oxidation on the morphology and chemical structure of FeOOH/rGO was studied using scanning electron microscopy, Raman spectroscopy, thermogravimetric analysis, and Brunauer-Emmett-Teller surface area analysis. The particle size of FeOOH crystallites was approximately 100 nm, and they were distributed uniformly on the surface and in the pores of FeOOH/rGO. FeOOH/rGO prepared with mildly oxidized graphite had fewer defects, higher specific surface area, and higher FeOOH content than FeOOH/rGO prepared with highly oxidized graphite. These features resulted in better electrochemical properties, such as larger specific capacitance and lower charge transfer resistance.
A previously developed ordinary differential equation (ODE) that models the dynamic interaction and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC) was used to explain the definitive treatment failure in Glioblastoma Multiforme (GBM) for conventionally and hypo-fractionated treatments. In this study, optimization of temporal dose modulation based on the ODE equation is performed to explore the feasibility of improving GBM treatment outcome.
A non-convex optimization problem with the objective of minimizing the total cancer cell number while maintaining the normal tissue biological effective dose (BEDnormal) at 100 Gy, equivalent to the conventional 2 Gy × 30 dosing scheme was formulated. With specified total number of dose fractions and treatment duration, the optimization was performed using a paired simulated annealing algorithm with fractional doses delivered to the CSC and DCC compartments and time intervals between fractions as variables. The recurrenceThe development and utilization of a temporal dose fractionation optimization framework in the context of CSC dynamics have demonstrated that substantial delay in GBM local tumor recurrence could be achieved with a super hyperfractionated treatment approach. MYF-01-37 in vivo Preclinical and clinical studies are needed to validate the efficacy of this novel treatment delivery method.A simulation model is developed to analyze the spread of covid-19 in universities. The model can be used to conduct a what-if analysis and estimate infection cases under different policies. For proof-of-concept, the model is simulated for a hypothetical university of 25,000 students and 3,000 faculty/staff in a U.S. college town. Simulation results show that early outbreaks are very likely, and there is no silver bullet to avoid them. Instead, a combination of policies should be carefully implemented. The results suggest (almost) full remote university operations from the beginning of the semester. In a less-preferred alternative, if universities decide to have students attend in person, they should encourage remote operations for high-risk individuals, conduct frequent rapid tests, enforce mask use, communicate with students and employees about the risks, and promote social distancing. Universities should be willing to move to remote operations if cases rise. Under this scenario, and considering implementation challenges, many universities are still likely to experience an early outbreak, and the likelihood of having a case of death is worrisome. In the long run, students and faculty react to the risks, and even if universities decide to continue operations, classes are likely to have very low in-person attendance. Overall, our analysis depicts several sources of system complexities, negative unintended consequences of relying on a single policy, non-linear incremental effects, and positive synergies of implementing multiple policies. A simulation platform for a what-if analysis is offered so marginal effectiveness of different policies and different decision-making thresholds for closure can be tested for universities of varying populations.
This study investigates the oral health-seeking behaviour of households and its influence on demand for dental caries treatment services in Enugu state Nigeria.
A quantitative descriptive cross-sectional study was used to explore the oral health seeking pattern of 378 urban and 348 rural household respondents in Enugu state Nigeria. The study explored dental caries treatment-seeking, oral health behavior of respondents using the three dynamics of the Andersen and Newman health utilization model; predisposing, enabling and need factors.
Recommendations from community members (48.9%), severity of disease (22.1%), and cost of treatment (19.4%) all influenced where oral healthcare was first sought. Gender and type of occupation, influenced positive oral health-seeking behavior (p<0.05). The least poor socioeconomic status (SES) group, sought dental treatment in the private dental clinics, while the very poor and most poor SES groups used traditional healers, home treatment and patent medicine dealers more.