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.

This paper investigated a multi-objective order allocation planning problem in make-to-order manufacturing with the consideration of various real-world production features. A novel hybrid intelligent optimization model, integrating a multi-objective memetic optimization (MOMO) process, a Monte Carlo simulation technique and a heuristic pruning technique, is developed to tackle this problem. The MOMO process, combining a NSGA-II optimization process with a tabu search, is proposed to provide Pareto optimal solutions. Extensive experiments based on industrial data are conducted to validate the proposed model. Results show that (1) the proposed model can effectively solve the investigated problem by providing effective production decision-making solutions; (2) the MOMO process has better capability of seeking global optimum than an NSGA-II-based optimization process and an industrial method.

A hybrid intelligent model for order allocation planning in make-to-order manufacturing

Aim:

To compare 1-week ranitidine bismuth citrate-based (RBC) triple therapy vs. omeprazole-based (O) triple therapy for the eradication of Helicobacter pylori infection in Hong Kong with high prevalence of metronidazole resistance.



Methods:

Patients with non-ulcer dyspepsia and H. pylori infection were randomized to receive either: (i) RBCCM: ranitidine bismuth citrate (pylorid) 400 mg, clarithromycin 250 mg and metronidazole 400 mg; or (ii) OCM: omeprazole 20 mg, clarithromycin 250 mg and metronidazole 400 mg, each given twice daily for 1 week. Endoscopy (CLO test, histology and culture) and 13C-urea breath test were performed before randomization and 6 weeks after drug treatment.



Results:

A total of 180 patients were randomized. H. pylori eradication rates (intention-to-treat, n=180/per protocol, n=166) were 83%/92% for RBCCM and 66%/70% for OCM (P=0.01, intention-to-treat and P=0.001, per protocol, respectively). RBCCM treatment was unaffected by metronidazole susceptibility and achieved a significantly higher eradication rate in metronidazole-resistant cases (89%) than the OCM group (45%, P=0.0064).



Conclusion:

One-week ranitidine bismuth citrate-based triple therapy is significantly better than omeprazole-based triple therapy for the eradication of H. pylori infection, especially in metronidazole-resistant cases. It is an effective regimen for the eradication of H. pylori infection in regions with a high prevalence of metronidazole resistance.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2036.2001.00932.x

One‐week ranitidine bismuth citrate‐based triple therapy for the eradication of Helicobacter pylori in Hong Kong with high prevalence of metronidazole resistance

Photon emission from rare gas ion bombardment of metal surfaces

Expression of vascular endothelial growth factor in von Hippel-Lindau syndrome-associated papillary cystadenoma of the epididymis

Six species of freshwater fish collected from 10 fishponds in Shunde and Zhongshan, China, four species of marine fishes collected from different mariculture farms [four in Hong Kong (Tung Lung Chau, Ma Wan, Cheung Chau and Kat O) and two in mainland China (Daya Bay and Shenzhen)] together with feed (both trash fish and commercial pellets) and sediment were analyzed for DDTs. Total DDTs in freshwater fish flesh decreased in the order of: carnivores [1742 μg/kg lipid weight (l.w.)] > herbivores (165 μg/kg, l.w.) > omnivores (42.5 μg/kg, l.w.), with the highest concentration detected in mandarin fish (Siniperca chuatsi) (2641 μg/kg, l.w.). For marine fish, snubnose pompano (Trachinotus blochii) and orange-spotted grouper (Epinephelus coioides) collected in Ma Wan contained elevated levels of total DDTs (2590 and 2034 μg/kg l.w., respectively). Trash fish used in both freshwater and marine fish farms contained significantly higher levels (86.5–641 μg/kg l.w.) (p < 0.05) of DDTs than in commercial pellets, but correlations between DDT levels in fish feed and muscle were not significant. The elevated biota-sediment accumulating factor for tilapia (Tilapia mossambicus) (24.1) indicated that accumulation of DDTs from sediment to the fish was evident. It can be concluded that trash fish should not be used for fish culture in order to lower the level of residual DDTs in fish muscle.

Suet Yi Leung

Papers

A hybrid intelligent model for order allocation planning in make-to-order manufacturing

One‐week ranitidine bismuth citrate‐based triple therapy for the eradication of Helicobacter pylori in Hong Kong with high prevalence of metronidazole resistance

Photon emission from rare gas ion bombardment of metal surfaces

Expression of vascular endothelial growth factor in von Hippel-Lindau syndrome-associated papillary cystadenoma of the epididymis

Risk Assessment of Residual DDTs in Freshwater and Marine Fish Cultivated Around the Pearl River Delta, China