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.

Global competition in the apparel trade has led to the emergence of a tier of production organisers based in Hong Kong, Taiwan, and other Asian countries. These organisers are playing an active role, by using global resources, in managing the flow of physical goods and co-ordinating production for Western importers. They have been the leaders in supplying garments to world markets in past decades. However, as pointed out in this paper, their robustness has been constrained by the industrial structure and culture. Although they have had years of experience in managing supply, their exposure to handling demand has been limited. In an era focusing on meeting customer's needs, whether or not their strengths can sustain their leadership is in question. This paper therefore proposes a model of world-class sourcing enterprises for the purpose of promoting sourcing centres to develop skills in supply-chain management.

World-class apparel-sourcing enterprises and the restructuring of existing global supply chains

The growth of InP by atmospheric pressure Metal-Organic Chemical Vapor Deposition using trimethyl indium (TMIn) and PH3 sources is demonstrated. No evidence was found to suggest depletion of TMIn due to a TMIn-PH3 reaction in the gas phase. It was found, however, that TMIn can, under certain growth conditions, be significantly depleted due to premature gas phase pyrolysis. Decreasing the gas temperature by either increasing the total flow rate or by using a lower thermal conductivity gas was found to decrease the amount of TMIn gas phase pyrolysis and increase the growth rate. It was also found that as the gas becomes cooler and the reactants are used more efficiently in the epitaxial growth, the film morphology improves significantly to a point at which smooth, specular surfaces can be routinely grown.

The effect of gas temperature on the growth of InP by atomspheric pressure metal-organic chemical vapor deposition using trimethyl indium and PH3 sources

Lattice dynamics of graphite intercalation compounds

Six cases of post-infectious encephalomyelitis are described. A preceding non-specific viral-like illness occurred 4 to 20 days before the onset of the neurological deficits. The clinical syndromes included transverse myelitis, focal encephalitis and encephalomyelitis (each in one case) and diffuse encephalitis in 3. Magnetic resonance imaging appeared to be the investigation of choice. High dose corticosteroids were given to 4 patients who recovered partially or fully. The patient with focal encephalitis had a spontaneous and complete recovery. The remaining patient with diffuse encephalitis died 3 days after the onset; autopsy showed prominent lymphocytic perivascular cuffing in the white matter and lymphocytic infiltration of the meninges.

Postinfectious myelitis, encephalitis and encephalomyelitis.

Background and Aim: Conventional [13C]-urea breath test ([13C]-UBT) requires prior fasting and a test meal, which theoretically improves the accuracy of the test. However, recent studies have suggested that prior fasting and test meal may not be essential. We aimed to determine the accuracy of a new [13C]-UBT protocol without fasting in Chinese.



Methods: Dyspeptic patients referred for upper endoscopy were recruited. The gold standard for Helicobacter pylori infection was the combination of Campylobacter-like organism (CLO) test and histology. Group I (n = 213) patients underwent [13C]-UBT with prior fasting and with citrate acid test meal. Group II (n = 123) patients underwent [13C]-UBT without prior fasting but with test meal. Group III (n = 90) patients underwent [13C]-UBT without prior fasting and without test meal.



Results: The highest accuracy for groups I, II and III was 96.7, 95.1 and 95.5% using a cut-off value of 5.0, 5.5 and 3.5, respectively. The sensitivities and specificities were 97.4 and 95.8% in group I, 93.3 and 96.8% in group II, and 96.5 and 93.9% in group III, respectively.



Conclusion: The [13C]-UBT protocols without prior fasting and either with or without test meal produce highly accurate and reliable results in the Chinese population.

Suet Yi Leung

Papers

World-class apparel-sourcing enterprises and the restructuring of existing global supply chains

The effect of gas temperature on the growth of InP by atomspheric pressure metal-organic chemical vapor deposition using trimethyl indium and PH3 sources

Lattice dynamics of graphite intercalation compounds

Postinfectious myelitis, encephalitis and encephalomyelitis.

[13C]-urea breath test without prior fasting and without test meal is accurate for the detection of Helicobacter pylori infection in Chinese.