Optimization of solid culture conditions for TNF-α inhibitor qiaonanmycin via response surface methodology

目的利用响应面法对潜在的Tnf-α抑制剂桥南霉素固态发酵培养基进行优化。方法用HPlC做检测方法,以桥南霉素的洗脱峰面积为指标,先通过PlACkETT-burMAn(P-b)实验筛选出影响固态发酵产量的主要因素,进而进行单因素优化实验和响应面中心组合设计实验,确定主要影响因素的最佳浓度,得到最优的固体发酵培养基组成。结果优化后的发酵培养基组成:土豆400g/l、葡萄糖35g/l、蛋白胨10.5g/l、(nH4)2SO4 0.6g/l。按此配方固态发酵10l,对得到的粗提物进行HPlC检测,桥南霉素的实际产量为4.3Mg/l,与模型的理论值基本相符,较优化前的产量1.5Mg/l提高了186.7%。结论响应面方法是一种有效的培养基优化方法,经此优化方法桥南霉素的产量得到了较大的提高。Objective The solid fermentation culture conditions of compound qiaonanmycin were optimized via response surface methodology.Methods Based on quantitative detection method of qiaonanmycin by HPLC, the key fermentation factors were determined via P-B test, then their optimized concentrations were confirmed through response face method.Results The optimum solid fermentation culture medium compositions of qiaonanmycin were: potato 400g/L, dextrose 35g/L, peptone 10.5g/L, and(NH4)2SO4 0.6g/L.Under this condition, the yield of qiaonanmycin was 4.3mg/L, resulting in a 186.7% increase comparing with original production yield, and the optimized yield was consistent well with theoretical value predicted by response face method.Conclusion The optimized solid fermentation culture conditions were reliable and repeatable, it was warranted for large-scale fermentation process.中央高校基本业务费(No.2010121092); 厦门市科技计划项目(No.3502Z20123010

中国物理海洋学研究70年：发展历程、学术成就概览

本文概略评述新中国成立70年来物理海洋学各分支研究领域的发展历程和若干学术成就。中国物理海洋学研究起步于海浪、潮汐、近海环流与水团,以及以风暴潮为主的海洋气象灾害的研究。随着国力的增强,研究领域不断拓展,涌现了大量具有广泛影响力的研究成果,其中包括:提出了被国际广泛采用的"普遍风浪谱"和"涌浪谱",发展了第三代海浪数值模式;提出了"准调和分析方法"和"潮汐潮流永久预报"等潮汐潮流的分析和预报方法;发现并命名了"棉兰老潜流",揭示了东海黑潮的多核结构及其多尺度变异机理等,系统描述了太平洋西边界流系;提出了印度尼西亚贯穿流的南海分支(或称南海贯穿流);不断完善了中国近海陆架环流系统,在南海环流、黑潮及其分支、台湾暖流、闽浙沿岸流、黄海冷水团环流、黄海暖流、渤海环流,以及陆架波方面均取得了深刻的认识;从大气桥和海洋桥两个方面对太平洋–印度洋–大西洋洋际相互作用进行了系统的总结;发展了浅海水团的研究方法,基本摸清了中国近海水团的分布和消长特征与机制,在大洋和极地水团分布及运动研究方面也做出了重要贡献;阐明了南海中尺度涡的宏观特征和生成机制,揭示了中尺度涡的三维结构,定量评估了其全球物质与能量输运能力;基本摸清了中国近海海洋锋的空间分布和季节变化特征,提出了地形、正压不稳定和斜压不稳定等锋面动力学机制;构建了"南海内波潜标观测网",实现了对内波生成–演变–消亡全过程机理的系统认识;发展了湍流的剪切不稳定理论,提出了海流"边缘不稳定"的概念,开发了海洋湍流模式,提出了湍流混合参数化的新方法等;在海洋内部混合机制和能量来源方面取得了新的认识,并阐述了混合对海洋深层环流、营养物质输运等过程的影响;研发了全球浪–潮–流耦合模式,推出一系列海洋与气候模式;发展了可同化主要海洋观测数据的海洋数据同化系统和用于ENSO预报的耦合同化系统;建立了达到国际水准的非地转(水槽/水池)和地转(旋转平台)物理模型实验平台;发展了ENSO预报的误差分析方法,建立了海洋和气候系统年代际变化的理论体系,揭示了中深层海洋对全球气候变化的响应;初步建成了中国近海海洋观测网;持续开展南北极调查研究;建立了台风、风暴潮、巨浪和海啸的业务化预报系统,为中国气象减灾提供保障;突破了国外的海洋技术封锁,研发了万米水深的深水水听器和海洋光学特性系列测量仪器;建立了溢油、危险化学品漂移扩散等预测模型,为伴随海洋资源开发所带来的风险事故的应急处理和预警预报提供科学支撑。文中引用的大量学术成果文献(每位第一作者优选不超过3篇)显示,经过70年的发展,中国物理海洋学研究培养了一支实力雄厚的科研队伍,这是最宝贵的成果。这支队伍必将成为中国物理海洋学研究攀登新高峰的主力军

Fixed-time attitude control for rigid spacecraft with external disturbances

针对受干扰的航天器姿态稳定控制问题，给出一种基于固定时间概念的有限时间控制方法使姿态快速收敛到平衡点。已有的基于终端滑模的有限时间控制方法，其估计的收敛时间都依赖于系统状态的初值，而本文基于固定时间设计的滑模面和趋近律，不仅使系统具有更快的收敛速度，且在不知道状态初值的情况下亦可估算出系统状态到达滑模面的时间和在滑模面上滑动的时间。而当状态初值已知时，本文亦给出了更为精确收敛时间的估算方法。最后，将设计的固定时间控制器应用于航天器姿态稳定控制，仿真结果表明该控制器能有效抑制外部干扰，且对状态初值具有很强的鲁棒性

微囊藻毒素与自然水体中细菌VIVIFORM状态的相关性

细菌VIVIFORM状态是直接关系到自然水体水质评价和环境保护的生态现象 ,其形成机理相当复杂 ,但环境胁迫是主要诱因。通过人为改变湖水中的微囊藻毒素 (MC LR)水平 ,对水体中蓝藻毒素与细菌VIVIFORM状态之间的相关性进行了分析。结果表明 ,较高的毒素水平对水体中细菌种群总量没有明显的影响 ,但能刺激VIVIFORM细菌转化成可培养状态 ,从而证实了自然水体中蓝藻毒素与水细菌VIVIFORM状态之间存在直接的相关性

Aripiprazole versus other atypical antipsychotics for schizophrenia

BACKGROUND: In most western industrialised countries, second generation (atypical) antipsychotics are recommended as first line drug treatments for people with schizophrenia. In this review we specifically examine how the efficacy and tolerability of one such agent - aripiprazole - differs from that of other comparable second generation antipsychotics. OBJECTIVES: To evaluate the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (November 2011), inspected references of all identified studies for further trials, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. SELECTION CRITERIA: We included all randomised clinical trials (RCTs) comparing aripiprazole (oral) with oral and parenteral forms of amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine for people with schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. Where possible, we calculated illustrative comparative risks for primary outcomes. For continuous data, we calculated mean differences (MD), again based on a random-effects model. We assessed risk of bias for each included study. MAIN RESULTS: We included 12 trials involving 6389 patients. Aripiprazole was compared to olanzapine, risperidone and ziprasidone. All trials were sponsored by an interested drug manufacturer. The overall number of participants leaving studies early was 30% to 40%, limiting validity (no differences between groups).When compared with olanzapine no differences were apparent for global state (no clinically important change: n = 703, 1 RCT, RR short-term 1.00 95% CI 0.81 to 1.22; n = 317, 1 RCT, RR medium-term 1.08 95% CI 0.95 to 1.22) but mental state tended to favour olanzapine (n = 1360, 3 RCTs, MD total Positive and Negative Syndrome Scale (PANSS) 4.68 95% CI 2.21 to 7.16). There was no significant difference in extrapyramidal symptoms (n = 529, 2 RCTs, RR 0.99 95% CI 0.62 to 1.59) but fewer in the aripiprazole group had increased cholesterol levels (n = 223, 1 RCT, RR 0.32 95% CI 0.19 to 0.54) or weight gain of 7% or more of total body weight (n = 1095, 3 RCTs, RR 0.39 95% CI 0.28 to 0.54).When compared with risperidone, aripiprazole showed no advantage in terms of global state (n = 384, 2 RCTs, RR no important improvement 1.14 95% CI 0.81 to 1.60) or mental state (n = 372, 2 RCTs, MD total PANSS 1.50 95% CI -2.96 to 5.96).One study compared aripiprazole with ziprasidone (n = 247) and both the groups reported similar change in the global state (n = 247, 1 RCT, MD average change in Clinical Global Impression-Severity (CGI-S) score -0.03 95% CI -0.28 to 0.22) and mental state (n = 247, 1 RCT, MD change PANSS -3.00 95% CI -7.29 to 1.29).When compared with any one of several new generation antipsychotic drugs the aripiprazole group showed improvement in global state in energy (n = 523, 1 RCT, RR 0.69 95% CI 0.56 to 0.84), mood (n = 523, 1 RCT, RR 0.77 95% CI 0.65 to 0.92), negative symptoms (n = 523, 1 RCT, RR 0.82 95% CI 0.68 to 0.99), somnolence (n = 523, 1 RCT, RR 0.80 95% CI 0.69 to 0.93) and weight gain (n = 523, 1 RCT, RR 0.84 95% CI 0.76 to 0.94). Significantly more people given aripiprazole reported symptoms of nausea (n = 2881, 3 RCTs, RR 3.13 95% CI 2.12 to 4.61) but weight gain (7% or more of total body weight) was less common in people allocated aripiprazole (n = 330, 1 RCT, RR 0.35 95% CI 0.19 to 0.64). Aripiprazole may have value in aggression but data are limited. This will be the focus of another review. AUTHORS' CONCLUSIONS: Information on all comparisons are of limited quality, are incomplete and problematic to apply clinically. Aripiprazole is an antipsychotic drug with a variant but not absent adverse effect profile. Long-term data are sparse and there is considerable scope for another update of this review as new data emerges from the many Chinese studies as well as from ongoing larger, independent pragmatic trials

JUNO Sensitivity on Proton Decay p→νˉK+p\to \bar\nu K^+ Searches

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this paper, the potential on searching for proton decay in $p\to \bar\nu K^+$ mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits to suppress the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar\nu K^+$ is 36.9% with a background level of 0.2 events after 10 years of data taking. The estimated sensitivity based on 200 kton-years exposure is $9.6 \times 10^{33}$ years, competitive with the current best limits on the proton lifetime in this channel

JUNO sensitivity on proton decay p → ν K + searches*

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this study, the potential of searching for proton decay in the $p\to \bar{\nu} K^+$ mode with JUNO is investigated. The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar{\nu} K^+$ is 36.9% ± 4.9% with a background level of $0.2\pm 0.05({\rm syst})\pm$$0.2({\rm stat})$ events after 10 years of data collection. The estimated sensitivity based on 200 kton-years of exposure is $9.6 \times 10^{33}$ years, which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies