Multiscale Simulation of Surface Defect Influence in Nanoindentation by a Quasi-Continuum Method

Microscopic properties of crystal aluminum thin film have been investigated using the quasi-continuum method in order to study the influence of surface defects in nanoindentation. Various distances between the surface pit defect and indenter and various sizes of the pit have been calculated. In this simulation, as the distance between the pit and indenter increases, the nanohardness increases in a wave that goes up in a period of three atoms, and it is found closely related to the crystal structure of periodic atom arrangement on {1 1 1} atomic close-packed planes of FCC metal; there is almost no influence on the nanohardness when the adjacent distance between the pit and indenter is more than 16 atomic spacing. We have modified the theoretical equation of the necessary load for elastic-to-plastic transition of Al film with the initial surface defect size. Furthermore, when the size coefficient of width (of height) equals about one unit (half unit), the yield load experiences an obvious drop. When it reaches about two units (one unit), the yield load is nearly close to that of the nanoindentation on a stepped surface. Additionally, compared to the width, the height of surface pit defect displays a greater influence on the yield load of thin film

The Change of Left Ventricular Function in Rats with Subclinical Hypothyroid and the Effects of Thyroxine Replacement

Objective. The main purpose of this study was to explore the relationships between serca2a, Ryr2, adipokines, and the left ventricular function in the subclinical hypothyroidism with different TSH levels and to determine the impact of L-T4 treatment on these indexes. Methods. Sixty-five male Wistar rats were randomly divided into five groups: control group; sHT A, B, and C group; and sHT + T4 group. The sHT rats were induced by methimazole (MMI), and the sHT + T4 rats were administered with L-T4 treatment after 8 weeks of MMI administration. Serum TT4, TSH, APN, chemerin, and TNF-α were detected by radioimmunoassay kits and ELISA kits; left ventricular function was measured by PowerLab system via subclavian artery catheter. The expression of Serca2a, Ryr2, APN, chemerin, and TNF-α were detected by RT-PCR, Western blot, and immunohistochemistry. Results. The sHT groups had significantly higher TSH, chemerin, and TNF-α and lower Serca2a, Ryr2, and APN. The left ventricular pressure and heart rate in sHT groups were significantly lower in control and sHT + T4 group. Histopathological examination revealed the pathological changes in the sHT rats’ heart. L-T4 administration reduced TSH level and improved left ventricular function. Conclusions. TSH can impair left ventricular function by regulating several factors, and L-T4 treatment ameliorates it in sHT rats

Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials

Introduction: FLT3 mutations are closely associated with the occurrence of hematological and solid malignancies, especially with acute myeloid leukemia. Currently, several FLT3 inhibitors are in clinical trials, and some have been applied in clinic. However, the safety, efficacy and pharmacodynamics of these FLT3 inhibitors have not been systemically analyzed before.Methods: We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023.Results: Our results showed the most common adverse events (AEs) were gastrointestinal adverse reactions, including diarrhea, hand-foot syndrome and nausea, while the most common hematological AEs were febrile neutropenia, anemia, and thrombocytopenia. Based on the published data, the mean overall survival (OS) and the mean progression-free survival (PFS) were 9.639 and 5.905 months, respectively. The incidence of overall response rate (ORR), complete remission (CR), partial response (PR), and stable disease (SD) for all these FLT3 inhibitors was 29.0%, 8.7%, 16.0%, and 42.3%, respectively. The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration (Tmax) in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life (T1/2) range was highly variable, from 6.8 to 151.8 h.Discussion: FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication

The oyster genome reveals stress adaptation and complexity of shell formation

The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa. © 2012 Macmillan Publishers Limited. All rights reserved

A global reference for human genetic variation

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies

An SCM-G2SFCA Model for Studying Spatial Accessibility of Urban Parks

The urban park is the main leisure and entertainment place in residents’ daily lives. The accessibility of parks is closely related to the physical and mental health of the residents. Although many scholars have conducted a great deal of research on the spatial accessibility of urban parks, they have rarely considered the supply competition among different parks and the impact of multiple travel modes on the spatial accessibility of parks. Therefore, based on Baidu map navigation data, in this paper, the park Baidu score is used to represent the competitive relationship among different parks, and the impact of multiple travel modes on the spatial accessibility of parks is considered. A supply competition and multiple travel modes Gaussian two-step floating catchment area (SCM-G2SFCA) model is established to evaluate the spatial accessibility of the parks in the Wuhou District, Chengdu, China. The results show that (1) compared with traditional methods, the SCM-G2SFCA model can obtain more accurate results using Baidu map navigation data. (2) There are obvious spatial differences in the accessibility distribution of the parks in the Wuhou District, Chengdu, with high accessibility in the south and low accessibility in the north. The Jinyang and Huaxing sub-districts in the southern suburbs have the highest park accessibility and can obtain more adequate park services. The Fangcaojie and Cujin sub-districts in the northern urban areas have the lowest park accessibility and are relatively lacking in park services. The research results of this study have important reference value for the rational planning of urban parks and the improvement of the spatial accessibility of urban parks in the Wuhou District of Chengdu and similar urban areas

Hopf Bifurcation and Hybrid Control of a Delayed Ecoepidemiological Model with Nonlinear Incidence Rate and Holling Type II Functional Response

Hopf bifurcation analysis of a delayed ecoepidemiological model with nonlinear incidence rate and Holling type II functional response is investigated. By analyzing the corresponding characteristic equations, the conditions for the stability and existence of Hopf bifurcation for the system are obtained. In addition, a hybrid control strategy is proposed to postpone the onset of an inherent bifurcation of the system. By utilizing normal form method and center manifold theorem, the explicit formulas that determine the direction of Hopf bifurcation and the stability of bifurcating period solutions of the controlled system are derived. Finally, some numerical simulation examples confirm that the hybrid controller is efficient in controlling Hopf bifurcation

Multiscale Analysis of Size Effect of Surface Pit Defect in Nanoindentation

The nanoindentation on a pit surface has been simulated using the quasicontinuum method in order to investigate the size effect of surface pit defect on the yield load of thin film. Various widths and heights of surface pit defect have been taken into account. The size coefficient has been defined as an index to express the influence of the width or height of surface pit defect. The results show that as the size coefficient of width (of height) increases, at first the yield load of thin film decreases extremely slowly, until the size coefficient of width equals approximately one unit (half unit), at which point the yield load experiences an obvious drop. When the size coefficient of width (of height) reaches approximately two units (one unit), the yield load is almost the same as that of the nanoindentation on a stepped surface. In addition, the height of surface pit defect has more influence than the width on the yield load of thin film

The Change of Left Ventricular Function in Rats with Subclinical Hypothyroid and the Effects of Thyroxine Replacement

Objective. The main purpose of this study was to explore the relationships between serca2a, Ryr2, adipokines, and the left ventricular function in the subclinical hypothyroidism with different TSH levels and to determine the impact of L-T4 treatment on these indexes. Methods. Sixty-five male Wistar rats were randomly divided into five groups: control group; sHT A, B, and C group; and sHT + T4 group. The sHT rats were induced by methimazole (MMI), and the sHT + T4 rats were administered with L-T4 treatment after 8 weeks of MMI administration. Serum TT4, TSH, APN, chemerin, and TNF-α were detected by radioimmunoassay kits and ELISA kits; left ventricular function was measured by PowerLab system via subclavian artery catheter. The expression of Serca2a, Ryr2, APN, chemerin, and TNF-α were detected by RT-PCR, Western blot, and immunohistochemistry. Results. The sHT groups had significantly higher TSH, chemerin, and TNF-α and lower Serca2a, Ryr2, and APN. The left ventricular pressure and heart rate in sHT groups were significantly lower in control and sHT + T4 group. Histopathological examination revealed the pathological changes in the sHT rats’ heart. L-T4 administration reduced TSH level and improved left ventricular function. Conclusions. TSH can impair left ventricular function by regulating several factors, and L-T4 treatment ameliorates it in sHT rats