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Mutations of the Regulatory Factor X5 (RFX5) have been associated with the autosomal recessive major histocompatibility class II (MHC-II) deficiency, which is a severe immunodeficiency characterized by constitutive and interferon-gamma induced MHC II expression disorder and leads to the absence of cellular and humoral T-cell response to antigen challenge. The compound heterozygous splicing mutations of RFX5: c.353 + 6T>G (maternally inherited) and c.757 + 1G>A (paternally inherited) were identified in an infant diagnosed severe immunodeficiency. The mutation c.757 + 1G>A was classified as likely pathogenic while c.353 + 6T>G was classified as the variant of uncertain significance according to American College of Medical Genetics and Genomics (ACMG). To investigate the pathogenicity of RFX5: c.353 + 6T>G, reverse transcription PCR (RT-PCR) was conducted with the mother’s peripheral blood. An insertion of 191-bp intronic sequence (intron 6) was found in the transcripts, and this resulted in a frameshift and premature truncation of the protein, especially reduced the DNA-binding domain (DBD) of the RFX5 protein. Our data expanded the spectrum of pathogenic mutations in MHC-II deficiency and put new insights into the genetic counseling, prenatal diagnosis and preimplantation genetic testing (PGT) for the disease.

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Conventional arc-melting and casting is the most widely used synthesis method of high-entropy alloys (HEAs). However, the extremely high melting temperature and repetitious melting processes cause the evaporation of some constituent elements with a low melting temperature, resulting in inaccurateness of composition. In this work, in-situ high throughput synthesis of FeCoNiCrCuAlx was carried out in the transmission electron microscope. The dynamic melting process of FeCoNiCrCu with Al was recorded, and the composition of FeCoNiCrCuAlx was examined by an energy dispersive spectrometer. The in-situ high throughput method provides a novel way to prepare HEA samples efficiently.

The twinning mechanism in an FeCoNiCrAl0.1 high-entropy alloy was investigated by in-situ transmission electron microscopy. Deformation twins were commonly found on the conjugate plane and were produced by twinning dislocation gliding on every adjacent (111) plane layer by layer. The twinning dislocations were Shockley partials and were generated from the cross-slip.

In oncology clinical trials, characterizing the long-term overall survival (OS) benefit for an experimental drug or treatment regimen (experimental group) is often unobservable if some patients in the control group switch to drugs in the experimental group and/or other cancer treatments after disease progression. A key question often raised by payers and reimbursement agencies is how to estimate the true benefit of the experimental drug group on overall survival that would have been estimated if there were no treatment switches. Several commonly used statistical methods are available to estimate overall survival benefit while adjusting for treatment switching, ranging from naive exclusion or censoring approaches to more advanced methods including inverse probability of censoring weighting (IPCW), iterative parameter estimation (IPE) algorithm or rank-preserving structural failure time models (RPSFTM). However, many clinical trials now have patients switching to different treatment regimens other than the test drugs, and the existing methods cannot handle more complicated scenarios. To address this challenge, we propose two additional methods: stratified RPSFTM and random-forest-based prediction. A simulation study is conducted to assess the properties of the existing methods along with the two newly proposed approaches.

Cu–Ag alloys have much higher strength than that predicted by the usual mixture rule and attract intense attention. Although many researches on their strengthening mechanism were carried out, quantitative analysis of the ultra-strong strengthening effect of Ag precipitates is still a challenge. In this study, Cu, Cu-2 wt.% Ag and Cu-6 wt.% Ag were selected to bring to light the mechanism in remarkable strengthening effect of Ag alloying by relating the mechanical properties and the microstructure of the tested materials. A preliminary quantitative approach is proposed to predict the strength of Cu–Ag alloys with given composition and drawing strain.

The author discusses five main differences between archives in the United States and China: differences in national history and the formation of archives; differences in the archival administration system; differences in archival management; differences in the research use of archives; and differences in archival education. He remarks on some strengths and weaknesses, as he sees them, in the American archival system.