抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

http://ggdpathway.wustl.edu/files/2014/08/ACMG-Guidelines-2015_Richards-et-al.pdf

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

BACKGROUND Most patients with non-small-cell lung cancer have no response to the tyrosine kinase inhibitor gefitinib, which targets the epidermal growth factor receptor (EGFR). However, about 10 percent of patients have a rapid and often dramatic clinical response. The molecular mechanisms underlying sensitivity to gefitinib are unknown. METHODS We searched for mutations in the EGFR gene in primary tumors from patients with non-small-cell lung cancer who had a response to gefitinib, those who did not have a response, and those who had not been exposed to gefitinib. The functional consequences of identified mutations were evaluated after the mutant proteins were expressed in cultured cells. RESULTS Somatic mutations were identified in the tyrosine kinase domain of the EGFR gene in eight of nine patients with gefitinib-responsive lung cancer, as compared with none of the seven patients with no response (P<0.001). Mutations were either small, in-frame deletions or amino acid substitutions clustered around the ATP-binding pocket of the tyrosine kinase domain. Similar mutations were detected in tumors from 2 of 25 patients with primary non-small-cell lung cancer who had not been exposed to gefitinib (8 percent). All mutations were heterozygous, and identical mutations were observed in multiple patients, suggesting an additive specific gain of function. In vitro, EGFR mutants demonstrated enhanced tyrosine kinase activity in response to epidermal growth factor and increased sensitivity to inhibition by gefitinib. CONCLUSIONS A subgroup of patients with non-small-cell lung cancer have specific mutations in the EGFR gene, which correlate with clinical responsiveness to the tyrosine kinase inhibitor gefitinib. These mutations lead to increased growth factor signaling and confer susceptibility to the inhibitor. Screening for such mutations in lung cancers may identify patients who will have a response to gefitinib.

/pdf/activating-mutations-in-the-epidermal-growth-factor-receptor-4a7r2t8eq0.pdf

Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib

Receptor tyrosine kinase genes were sequenced in nonsmall cell lung cancer (NSCLC) and matched normal tissue. Somatic mutations of the epidermal growth factor receptor gene EGFR were found in 15 of 58 unselected tumors from Japan and 1 of 61 from the United States. Treatment with the EGFR kinase inhibitor gefitinib (Iressa) causes tumor regression in some patients with NSCLC, more frequently in Japan. EGFR mutations were found in additional lung cancer samples from U.S. patients who responded to gefitinib therapy and in a lung adenocarcinoma cell line that was hypersensitive to growth inhibition by gefitinib, but not in gefitinibinsensitive tumors or cell lines. These results suggest that EGFR mutations may predict sensitivity to gefitinib. Protein kinase activation by somatic mutation or

https://science.sciencemag.org/content/sci/early/2004/04/29/science.1099314.full.pdf

EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.

The new WHO classification of CNS tumours: a selective review

Layer thickness uniformity in liquid phase epitaxy: A two-dimensional diffusion analysis

This study was conducted to determine if dieldrin concentrations in water and fish of the Des Moines River, Iowa, decreased after registration of the compound was withdrawn by the Environmental Protection Agency in 1975. Mean June concentrations of dieldrin in river water decreased from 50 ppt in 1971 to 11 ppt in 1978. Average daily transport of dieldrin was 156 g in 1971 and 70 g in 1978. July levels in channel catfish muscle were 75 ppb in 1973 and 46 ppb in 1978. Dieldrin was still present in significant concentrations in the aquatic system 3 years after registration withdrawal.

Persistence of dieldrin water and channel catfish from the Des Moines River, Iowa, 1971-73 and 1978.

In this paper, a multi-objective scheduling problem of the multi- and mixed-model apparel assembly line (MMAAL) is investigated. A bi-level genetic algorithm is developed to solve the scheduling problem, in which a new chromosome representation is proposed to represent the flexible operation assignment including assigning one operation to multiple workstations as well as assigning multiple operations to one workstation. The proposed algorithm is validated using real-world production data and the experimental results show that the proposed algorithm can solve the proposed scheduling problem effectively.

A bi-level genetic algorithm for multi-objective scheduling of multi- and mixed-model apparel assembly lines

Nasopharyngeal carcinoma (NPC) is common in Southern Chinese and relatively young patients are affected [1] Despite being potentially treatable by irradiation, local recurrence and metastases are lifethreatening Dermatomyositis (DM), urticarial vasculitis, pulmonary osteoarthropathy, clubbing of fingers and myelemia are known paraneoplastic conditions associated with NPC [1] Paraneoplastic DM occur before, simultaneously or follow the diagnosis of NPC in 09–39% patients Up to 25% of malignancy detected in paraneoplastic DM was NPC Diagnosis of DM trigger aggressive search for underlying malignancy including NPC We reported a patient who developed paraneoplastic subacute predominantly motor polyneuropathy/polyradiculoneuropathy and inflammatory myopathy without skin rash simultaneously upon recurrence of NPC Case report

Suet Yi Leung

Papers

The new WHO classification of CNS tumours: a selective review

Layer thickness uniformity in liquid phase epitaxy: A two-dimensional diffusion analysis

Persistence of dieldrin water and channel catfish from the Des Moines River, Iowa, 1971-73 and 1978.

A bi-level genetic algorithm for multi-objective scheduling of multi- and mixed-model apparel assembly lines

Paraneoplastic motor neuropathy and inflammatory myopathy associated with nasopharyngeal carcinoma