Distinct genomic traits of acral and mucosal melanomas revealed by targeted mutational profiling

The incidence of melanoma is rising globally including China. Comparing to Caucasians, the incidence of non‐cutaneous melanomas is significantly higher in Chinese. Herein, we performed genomic profiling of 89 Chinese surgically resected primary melanomas, including acral (n = 54), cutaneous (n = 22), and mucosal (n = 13), by hybrid capture‐based next‐generation sequencing. We show that mucosal melanomas tended to harbor more pathogenic mutations than other types of melanoma, though the biological significance of this finding remains uncertain. Chromosomal arm‐level alterations including 6q, 9p, and 10p/q loss were highly recurrent in all subtypes, but mucosal melanoma was significantly associated with increased genomic instability. Importantly, 7p gain significantly correlated with unfavorable clinical outcomes in non‐cutaneous melanomas, representing an intriguing prognostic biomarker of those subtypes. Furthermore, focal amplification of 4q12 (KIT, KDR, and PDGFRα) and RAD51 deletion were more abundant in mucosal melanoma, while NOTCH2 amplification was enriched in acral melanoma. Additionally, cutaneous melanomas had higher mutation load than acral melanomas, while mucosal melanomas did not differ from other subtypes in mutation burden. Together, our data revealed important features of acral and mucosal melanomas in Chinese including distinctive driver mutation pattern and increased genomic instability. These findings highlight the possibilities of combination therapies in the clinical management of melanoma.     

Interactions between the toxicity of the heavy metals cadmium,copper, zinc in combinations and the detoxifying role of calcium in the brown algaCystoseira barbata

The toxicity of three heavy metals, Cd, Cu and Zn, and the detoxifying role of Ca have been studied for the brown algaCystoseira barbata formaaurentia after a 4-week laboratory culture. The experimental design was based upon a complete factorial design 2^k, which seems to be the first time it has been used in algal physiology. It was demonstrated that these three elements, applied jointly, act on weight-growth, chlorophyll a, c and carotenoid synthesis and Cd, Cu and Zn uptake. Cd and Zn act in synergy or in antagony, depending on their exogenous concentrations, on chlorophyll a and on carotenoid synthesis. Zn is antagonistic towards Cd and Cu on weight-growth in the combination Cd-Cu-Zn. From different element combinations, the protective role of Ca appears evident on weight-growth (Cd-Zn-Ca and Cu-Ca), chlorophyll a (Cd-Cu-Ca and Cu-Zn-Ca), chlorophyll c (Cd-Ca), carotenoid synthesis (Cd-Cu-Ca and Cu-Zn-Ca), Cd and Cu uptake (Cd-Cu-Ca) and Zn uptake (Cu-Zn-Ca). This role is confirmed by cytological investigations. This is apparently the first report concerning a Ca interaction with toxicity of heavy metals applied in combinations. However, the mechanisms of tolerance remain unknown.     

Optimal design of non-Newtonian, micro-scale viscous pumps for biomedical devices

The present paper addresses the numerical optimization of geometrical parameters of non-Newtonian micro-scale viscous pumps for biomedical devices. The objective is to maximize the mass flow rate per unit of shaft power consumed by the rotor when an external pressure load is applied along the channel that houses the rotor. Two geometric parameters are considered in the optimization process: (i) the height of the channel that houses the rotor (H) and (ii), the eccentricity (epsilon) of the rotor. Three different micro-scale viscous pump configurations were tested: a straight-housed pump (I-shaped housing) and two curved housed pumps (L- and U-shaped housings). The stress-strain constitutive law is modeled by a power-law relation. The results show that the geometric optimization of micro-scale viscous pumps is critical since the mass flow rate propelled by the rotor is highly dependent on epsilon and H. Numerical simulations indicate that mass flow rate is maximized when epsilon approximately 0, namely when the rotor is placed at a distance of 0.05 radii from the lower wall. The results also show that micro-scale viscous pumps with curved housing provide higher mass flow rate per unit of shaft power consumed when compared with straight-housed pumps. The results are presented in terms optimized dimensions of all three configurations (i.e., H(opt) and epsilon(opt)) and for values of the power-law index varying between 0.5 (shear thinning fluids) and 1.5 (shear-thickening fluids).     

中季稻区稻田害虫—天敌—农药系统的模拟及其优化管理的研究(英文)

本文以中季稻区稻田主要害虫稻飞虱、稻纵卷叶螟和捕食天敌蜘蛛的田间系统调查资料为基础,以害虫—天敌—农药系统为研究对象,应用害虫管理系统工程的原理,处理害虫、捕食天敌与农药三者之间的关系。建立了稻纵叶螟—蜘蛛—甲胺磷和稻飞虱—蜘蛛—甲胺磷两系统优化管理模型,绘制了它们的优化反馈控制策略图,利用微机对系统进行最优监控。使用时输入当前田间害虫与天敌数量,就可对系统作出即时的预测和最优决策。该策略确立的控制害虫的最优性能指标,是使害虫对农作物的为害所造成的损失与防治费用之和最小,并且使害虫和天敌的数量处于系统平衡状态。文中比较分析了该策略与基于经济阈值的常规害虫管理策略,指出了新策略在害虫综合治理中对天敌数量进行控制和管理的作用及其意义。     

Lorvotuzumab mertansine,a CD56-targeting antibody-drug conjugate with potent antitumor activity against small cell lung cancer in human xenograft models

Lorvotuzumab mertansine (LM) is an antibody-drug conjugate composed of a humanized anti-CD56 antibody, lorvotuzumab, linked via a cleavable disulfide linker to the tubulin-binding maytansinoid DM1. CD56 is expressed on most small cell lung cancers (SCLC), providing a promising therapeutic target for treatment of this aggressive cancer, which has a poor five-year survival rate of only 5–10%. We performed immunohistochemical staining on SCLC tumor microarrays, which confirmed that CD56 is expressed at high levels on most (~74%) SCLC tumors. Conjugation of lorvotuzumab with DM1 did not alter its specific binding to cells and LM demonstrated potent target-dependent cytotoxicity against CD56-positive SCLC cells in vitro. The anti-tumor activity of LM was evaluated against SCLC xenograft models in mice, both as monotherapy and in combination with platinum/etoposide and paclitaxel/carboplatin. Dose-dependent and antigen-specific anti-tumor activity of LM monotherapy was demonstrated at doses as low as 3 mg/kg. LM was highly active in combination with standard-of-care platinum/etoposide therapies, even in relatively resistant xenograft models. LM demonstrated outstanding anti-tumor activity in combination with carboplatin/etoposide, with superior activity over chemotherapy alone when LM was used in combinations at significantly reduced doses (6-fold below the minimally efficacious dose for LM monotherapy). The combination of LM with carboplatin/paclitaxel was also highly active. This study provides the rationale for clinical evaluation of LM as a promising novel targeted therapy for SCLC, both as monotherapy and in combination with chemotherapy.     

非光合固碳微生物的碳源组合优化

二氧化碳(CO_2)过量排放而引起的全球变暖是目前全球面临的重大环境问题。微生物固碳是实现二氧化碳资源利用的一种重要方式。探索无需光照的高效固碳微生物对于更广泛环境条件下的微生物固碳具有重要意义。在从全球各大海域筛选富集出非光合微生物茵群的基础上,本文构建了在不同的电子供体条件下(铵和氢气)促进非光合微生物茵群生长的最佳混合碳源组合,得到如下结果:在以NH_4~+为电子供体的条件下,优化后的碳源组合为374.24 mgC/L碳酸钠(Na_2CO_3),54.76 mgC/L碳酸氢钠(NaHCO_3)和0 mgC/LCO_2时,最佳响应值TOC为3.06 mg/L。最佳响应值TOC低于以Na_2CO_3为单一碳源时,但高于以CO_2或NaHCO_3为单一碳源时;在以H_2为电子供体条件下,使用优化后的混合碳源为0.26 mg/L Na_2CO_3、0.59mg/L NaHCO_3和71.48mL/L CO_2时,非光合微生物菌群的固碳效率可达27.62 mg/L,较以CO_2为单一碳源提高35%左右。这可能意味着有H_2条件下非光合微生物菌群中的微生物可能以羟基丙酸固碳途径为主,而且多条固碳途径均能被混合菌群利用。     

浅论如何持续有效地推进产学研创新联盟合作

产学研创新战略联盟是提升产品市场竞争力的手段,它集合了产业链中各相关单位资源,提供了解决瓶颈技术的平台,利益分享。该文介绍了联盟创建、成员的选择、风险控制、日常管理、利益分享等方面的经验。     

Application of iterative robust model‐based optimal experimental design for the calibration of biocatalytic models

The aim of model calibration is to estimate unique parameter values from available experimental data, here applied to a biocatalytic process. The traditional approach of first gathering data followed by performing a model calibration is inefficient, since the information gathered during experimentation is not actively used to optimize the experimental design. By applying an iterative robust model‐based optimal experimental design, the limited amount of data collected is used to design additional informative experiments. The algorithm is used here to calibrate the initial reaction rate of an ω‐transaminase catalyzed reaction in a more accurate way. The parameter confidence region estimated from the Fisher Information Matrix is compared with the likelihood confidence region, which is not only more accurate but also a computationally more expensive method. As a result, an important deviation between both approaches is found, confirming that linearization methods should be applied with care for nonlinear models. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1278–1293, 2017     

Host strain influences on supercoiled plasmid DNA production in Escherichia coli: Implications for efficient design of large-scale processes

We set out to investigate if E. coli genotype plays a significant role in host strain selection for optimal processing of plasmid DNA based on both quality and quantity of supercoiling. Firstly 17 E. coli commercial and non-commercial strains were selected and their available genetic backgrounds were researched in the open literature. Growth characteristics of all the strains were considered and made impartial by using a common medium and growth condition platform. By keeping the growth conditions constant for each strain/plasmid combination, we are only looking at one variable which is the host strain. The second step was to attempt to correlate the findings with common genotype characteristics (e.g. mutations such as endA or recA). We found that one can screen the number of strains which are likely to give good productivity early on, before any further optimisation and verification is performed, both for small and large plasmids. Also, it is worth noting that complex plasmid interactions with each strain prevent the use of genotype alone in making an intelligent choice for supercoiling optimisation. This leads to a third optimisation step selecting a few of the potentially high performing strains based on high DNA yield and supercoiling, with a view to identify the factors which need improvement in strain design and bioreactor optimisation. We found that high specific growth rates of some strains did not affect the level of DNA supercoiling but did influence the total plasmid yield, potentially an important aspect in the design of fermentation strategy. Interestingly, a few host/plasmid combinations result in what appears to be runaway plasmid replication.