Multiscale modelling of heteroepitaxial thin films

Multiscale models are developed to investigate the evolution of heteroepitaxial thin films at high temperatures via surface diffusion. Continuum models for the kinetics and thermodynamics of these systems are derived from atomistic potentials in chapter 2. A modified Lennard-Jones potential is used to introduce a coordination dependence and model the effects of surface stress. Novel hybrid atomistic-continuum models are developed in chapter 3 to investigate the static elastic field around a surface step due to the discontinuity in surface stress. They have atomic scale resolution around the defect to capture the non-linear response in highly deformed areas. Far away from the discontinuity, classical linear elasticity is used. An analytic force dipole model and the more general finite element method are chosen to represent the continuum. The kinetics of surface evolution are then investigated using a fully atomistic off-lattice Kinetic Monte Carlo (KMC) model. This allows the atoms on the surface of an atomistic lattice statics simulation to evolve via diffusive events, and readily incorporates the non-linear effects of strain on the thermodynamics and kinetics of the system. The flattening process of a rough (sinusoidal) surface is considered in chapter 4. The results are then compared with a derivative microscopic step flow model in chapter 5, which is extended to consider asymmetric step kinetics. The parameters in the step flow model are obtained from the interatomic potentials and are used to determine estimates of the macroscopic surface mobilities. The evolution of strained surfaces is investigated in chapter 6 using the off-lattice KMC model. The surface is found to be stable below a certain strain magnitude, in contradiction of the predictions of conventional theories. A new theory based on a discontinuous (cusped) surface energy orientation function is proposed and found to explain the simulation results

Stratification Effects on Wind Characteristics over Two-Dimensional Steep Hills

This paper was reviewed and accepted by the APCWE-IX Programme Committee for Presentation at the 9th Asia-Pacific Conference on Wind Engineering, University of Auckland, Auckland, New Zealand, held from 3-7 December 2017

sj-docx-1-pmj-10.1177_02692163241238900 – Supplemental material for Death education interventions for people with advanced diseases and/or their family caregivers: A scoping review

Supplemental material, sj-docx-1-pmj-10.1177_02692163241238900 for Death education interventions for people with advanced diseases and/or their family caregivers: A scoping review by Tong Wang, Kin Cheung and Huilin Cheng in Palliative Medicine</p

The effect of p300 on the proliferation of HDPCs.

<p>(A) Cell growth curves of HDPC/p300, HDPC/p300-ΔHAT and HDPC/V cells were constructed with the results of the CCK8 assay. The growth curves showed that p300 does not have a significant effect on the proliferation of HDPCs. (B) The BrdU assay revealed no significant differences in the amount of DNA synthesized by HDPC/p300, HDPC/p300-ΔHAT and HDPC/V cells. Newly synthesized DNA is stained red by BrdU and nuclei are stained blue by DAPI. Procedures were performed as described in the text (n = 3). All results are presented as the means ± SD of three independent experiments.</p

The overexpression of p300 increases ALP activity and mineral formation in HDPCs.

<p>(A) HDPC/V, HDPC/p300 and HDPC/p300-ΔHAT cells were cultured for 3 days in normal growth medium or odontoblastic induction medium, and the ALP activity in these cells was measured. GM, normal growth medium; IM, odontoblastic induction medium. (B) The effect of p300 on the formation of mineralized nodules in HDPCs cultured in odontoblastic induction medium, as analyzed by alizarin red S staining on day 21(×100). a: HDPC/V; b: HDPC/p300; c: HDPC/p300-ΔHAT. Scale bar, 100 µm. d: The histogram shows the quantification of mineralization by densitometry and reveals that remarkable decreases in mineralization occurred in HDPC/p300 and HDPC/p300-ΔHAT cells relative to control cells. All results are presented as the means ± SD of three independent experiments. Procedures were performed as described in the text (n = 3). * Statistically significant difference relative to the control, <i>P</i><0.05.</p

CHIP assay shows that p300 binds to the promoter region of <i>OCN</i> and <i>DSPP</i> in HDPCs.

<p>(A, B) Cells were cross-linked with formaldehyde. Chromatin was immunoprecipitated with anti-p300 or anti-H3K9Ac antibodies. The chromatin was eluted, reverse cross-linked, and the eluted DNA was analyzed by PCR.</p

The stable overexpression of p300 and p300-ΔHAT in HDPCs.

<p>(A) real-time qPCR was performed to measure the relative levels of p300 and p300-ΔHAT mRNA after the transduction with lentiviral vectors. The level of each product was normalized to GAPDH mRNA levels. (B) Protein expression levels of p300 and p300-ΔHAT were assessed by western blotting analysis (right panel) and densitometric evaluation (left panel; expressed as ratio to GAPDH). The expression of GAPDH served as a control. All results are presented as the means ± SD of three independent experiments. Procedures were performed as described in the text (n = 3). * Statistically significant differences relative to the control, <i>P</i><0.05.</p

p300 regulates the expression of OCT4, NANOG and SOX2, whereas HAT mutant p300 suppresses the expression of NANOG and SOX2.

<p>(A) Real-time qPCR estimation of the relative endogenous mRNA levels of <i>OCT4, NANOG</i> and <i>SOX2</i> in HDPC/p300 and HDPC/V cells. The mRNA levels of each product were normalized to the mRNA levels of GAPDH. (B) Western blotting analysis (right panel) and densitometric evaluation (left panel; expressed as the ratio of protein levels to GAPDH levels) measuring the levels of OCT4, NANOG and SOX2 proteins in HDPC/p300 and HDPC/V cells. The expression of GAPDH was used as an internal control. (C) Measurement of the relative endogenous mRNA levels of <i>NANOG</i> and <i>SOX2</i> in HDPC/V, HDPC/p300 and HDPC/p300-ΔHAT cells using real-time qPCR. The mRNA levels of each product were normalized to GAPDH mRNA levels. (D) The results were further confirmed by western blotting (right panel) and densitometric evaluation (left panel; expressed as ratio to GAPDH). GAPDH was used as an internal control. All results are expressed as the means ± SD of three independent experiments. Procedures were performed as described in the text (n = 3). * Statistically significant difference relative to the control, <i>P</i><0.05.</p

Image_6_Transcranial magnetic stimulation effects on cognitive enhancement in mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis.TIF

IntroductionTranscranial magnetic stimulation (TMS) is a non-invasive intervention that holds promise for improving cognitive function in individuals with Alzheimer's disease (AD). However, the effectiveness of this therapy and the optimal TMS parameters has not reached a consensus. The purpose of the meta-analysis was to systematically discern the effectiveness of different components of TMS protocols on cognitive improvement in patients with mild cognitive impairment (MCI) and AD.MethodsThe meta-analysis was preregistered on Prospero (registration number: CRD42022345482). PubMed, Web of Science, Science Direct, and Cochrane Library databases were used to search, screen and identify eligible studies with the following keywords: Transcranial Magnetic Stimulation OR TMS OR theta burst stimulation AND Alzheimer OR Alzheimers OR Alzheimer's OR mild cognitive impairment OR MCI. Randomized controlled trials (RCTs) of participants with accepted standardized diagnostic criteria were searched by two authors independently. The risk of bias was assessed using an adapted Cochrane Risk of Bias tool. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated using the random-effects models. Subgroup analyses were performed to investigate the influential factors.ResultsA total of 21 studies and 25 trials were included in this meta-analysis. The findings revealed a significant overall cognition improvement of real stimulation compared with sham stimulation (short-term effects: SMD, 0.91; 95% CI 0.44–1.38; P ConclusionCognitive improvement effect of TMS was demonstrated in MCI and AD patients in both short-term assessment and long-lasting outcomes, and the efficiency of TMS is affected by the stimulation frequency, stimulation site, and participant characteristics. Further RCTs are needed to validate the findings of our subgroup analysis.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022345482, identifier: CRD42022345482.</p

Image_2_Transcranial magnetic stimulation effects on cognitive enhancement in mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis.TIF

IntroductionTranscranial magnetic stimulation (TMS) is a non-invasive intervention that holds promise for improving cognitive function in individuals with Alzheimer's disease (AD). However, the effectiveness of this therapy and the optimal TMS parameters has not reached a consensus. The purpose of the meta-analysis was to systematically discern the effectiveness of different components of TMS protocols on cognitive improvement in patients with mild cognitive impairment (MCI) and AD.MethodsThe meta-analysis was preregistered on Prospero (registration number: CRD42022345482). PubMed, Web of Science, Science Direct, and Cochrane Library databases were used to search, screen and identify eligible studies with the following keywords: Transcranial Magnetic Stimulation OR TMS OR theta burst stimulation AND Alzheimer OR Alzheimers OR Alzheimer's OR mild cognitive impairment OR MCI. Randomized controlled trials (RCTs) of participants with accepted standardized diagnostic criteria were searched by two authors independently. The risk of bias was assessed using an adapted Cochrane Risk of Bias tool. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated using the random-effects models. Subgroup analyses were performed to investigate the influential factors.ResultsA total of 21 studies and 25 trials were included in this meta-analysis. The findings revealed a significant overall cognition improvement of real stimulation compared with sham stimulation (short-term effects: SMD, 0.91; 95% CI 0.44–1.38; P ConclusionCognitive improvement effect of TMS was demonstrated in MCI and AD patients in both short-term assessment and long-lasting outcomes, and the efficiency of TMS is affected by the stimulation frequency, stimulation site, and participant characteristics. Further RCTs are needed to validate the findings of our subgroup analysis.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022345482, identifier: CRD42022345482.</p