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Design and thermodynamic analysis of a pathway enabling anaerobic production of poly-3-hydroxybutyrate in Escherichia coli

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synthetic and systems Biotechnology 2023年第4期8卷 629-639页

作者： Karel Olavarria Marco V.Becker Diana Z.sousa Mark C.M.van Loosdrecht s.aljoscha wahl Laboratory of Microbiology Wageningen University and ResearchStippenenweg 46708 WEWageningenThe Netherlands Centre for Living Technologies Eindhoven-Wageningen-Utrecht AlliancePrincetonlaan 63584 CBUtrechtThe Netherlands Department of Biotechnology Applied Sciences FacultyDelft University of Technologyvan der Maasweg 92629 HZDelftThe Netherlands Lehrstuhl für Bioverfahrenstechnik Friedrich-Alexander-Universit¨atPaul-Gordan-Strasse 391052ErlangenGermany

Utilizing anaerobic metabolisms for the production of biotechnologically relevant products presents potential advantages,such as increased yields and reduced energy ***,lower energy dissipation may indicate that certain reactions are operating closer to their thermodynamic *** stoichiometric analyses and genetic modifications are frequently employed in metabolic engineering,the use of thermodynamic tools to evaluate the feasibility of planned interventions is less *** this study,we propose a novel metabolic engineering strategy to achieve an efficient anaerobic production of poly-(R)-3-hydroxybutyrate(PHB)in the model organism Escherichia *** approach involves re-routing of two-thirds of the glycolytic flux through non-oxidative glycolysis and coupling PHB synthesis with NADH *** complemented our stoichiometric analysis with various thermodynamic approaches to assess the feasibility and the bottlenecks in the proposed engineered *** to our calculations,the main thermodynamic bottleneck are the reactions catalyzed by the acetoacetyl-CoAβ-ketothiolase(EC 2.***.1.9)and the acetoacetyl-CoA reductase(EC 1.***.1.36).Furthermore,we calculated thermodynamically consistent sets of kinetic parameters to determine the enzyme amounts required for sustaining the conversion *** the case of the engineered conversion route,the protein pool necessary to sustain the desired fluxes could account for 20%of the whole cell dry weight.

关键词： Pathway feasibility analysis Protein cost Anaerobic metabolism Engineered pathways Metabolite concentrations

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Management and treatment of bizarre open globe trauma in three steps:a case report

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International Journal of Ophthalmology(English edition) 2011年第2期4卷 218-219页

作者： Lala Ceklic slobodanka Latinovic aljoscha s.Neubauer Djoko Obucina Bobana Petrovic Clinical Center of Eastern sarajevo-Eye Clinic Kasindo Ludvig Maximillian Univeristy Eye Clinic

This is a case presentation of a very bizarre open globe trauma with anterior segment foreign body-fishing hook stuck in the cornea and iris. Complications due to this kind of eye trauma might be very hazardous and with serious impact on visual function. We are representing our approach and experience of three step management of this kind of eye injury: first-extract the foreign body, close and reconstruct the eyeball, second-fight inflammation, and third-restore the visual function by cataract surgery.

关键词： eye trauma anterior segment foreign body traumatic cataract

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Navigated laser in diabetic macular edema: the impact of reduced injection burden on patients and physicians-who wins and who loses?

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International Journal of Ophthalmology(English edition) 2019年第2期12卷 342-345页

作者： Jacob Menzler aljoscha Neubauer Focke Ziemssen Institute for Health and Pharmacoeconomics Private Practice Ophthalmology Center for Ophthalmology Eberhard-Karls University

We inquired the impact of reduced therapy discontinuation in diabetic macular edema(DME) on physician's revenue considering anti-vascular endothelial growth factor(VEGF) monotherapy and its combination with Navilas treatment. Data were collected on injection frequency, treatment discontinuation and reimbursement fees for DME treatment with anti-VEGF compared to anti-VEGF in combination with navigated laser. Based on these data an economic model was built to compare physicians revenue over a 5y period using either therapy for 4 European countries and the UsA. Due to patients' higher therapy adherence, physicians using navigated laser therapy with anti-VEGF generate similar or higher revenues compared to VEGF monotherapy in all analyzed countries. The use of Navilas decreases the patient's injection burden at the same clinical outcome, while the physician's revenue remained stable or increased. Therewith, therapy discontinuation in DME can be reduced using the combination therapy with Navilas.

关键词： diabetic macular edema laser therapy Navilas cost-effectiveness injection burden adherence

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Green-light fundus autofluorescence in diabetic macular edema

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International Journal of Ophthalmology(English edition) 2013年第1期6卷 75-80页

作者： Lukas Reznicek simeon Dabov Christos Haritoglou Anselm Kampik Marcus Kernt aljoscha s Neubauer Department of Ophthalmology Ludwig Maximilians University

AIM:To evaluate the role of central green-light fundus autofluorescence (FAF) in diabetic macular edema(DME). METHODs:A consecutive series of 92 study eyes with diabetic retinopathy were included. Out of those, 51 diabetic eyes had DME and were compared to 41 diabetic eyes without DME. In all subjects, green-light FAF images were obtained, quantified and classified into various FAF patterns. Cross-sectional optical coherence tomography (OCT) scans were obtained for evaluation of Inner/Outer segment (Is/Os) layer integrity, measurements of central RPE-Is/Os layer thickness as well as classification of DME into various subtypes. ·REsULTs:Meancentralgreen-lightFAFintensityofeyes with DME (1.289 ±0.140)log did not significantly differ from diabetic patients without DME (1.317 ±0.137)log. Most classifiable FAF patterns were seen in patients with cystoid DME. Mean central retinal thickness (CRT) of all study eyes with DME was (501.9±112.4)μm compared to (328.2±27.0)μm in diabetic patients without DME. Patients with DME had significantly more disrupted photoreceptor Is/Os layers than diabetic patients without DME (28/51 vs 5/41, P s/Os thickness of patients with DME (60.7±14.1)μm was significantly (Ps without DME (73.5 ±9.4)μm. Correlation analysis revealed non-significant correlations of green-light FAF intensity and OCT parameters in all subtypes of DME. ·CONCLUsION:Our results indicate a poor correlation of central green-light FAF intensity with CRT, Is/Os layer integrity or RPE-Is/Os layer thickness in diabetic patients with or without DME and its various subtypes. Thus, central green-light FAF is not suitable for detection of retinal thickening in DME.

关键词： diabetic macular edema fundus autofluorescence optical coherence tomography

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Correlation of leaking microaneurysms with retinal thickening in diabetic retinopathy

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International Journal of Ophthalmology(English edition) 2011年第3期4卷 269-271页

作者： Lukas Reznicek Marcus Kernt Christos Haritoglou Michael Ulbig Anselm Kampik aljoscha s Neubauer Department of Ophthalmology Ludwig-Maximilians University

AIM: To investigate the contribution of fluorescein angiographic leaking microaneurysms (leak-MA) versus non-leaking microaneurysms (non-leak-MA) to retinal thickening in diabetic ***: A consecutive series of 38 eyes from 24 patients with diabetic retinopathy was ***-MA and non-leak-MA in each eye were selected in pairs at corresponding topographic *** was defined by late phase fluorescein angiograms compared to early *** thickness was measured with Heidelberg spectralis OCT topographically aligned on early phase angiograms at the MA site and within a 1 mm ***: In all eyes,significant retinal thickening at the site of leaking compared to non-leaking microaneurysms was observed (356±69μm vs 318±56μm,P showing a mean increase in thickness in the areas of leak-MA vs non-leak-MA of 38±39μm (95% confidence interval 2551μm,Psurements also showed significant (Pss of leak-MA vs non-leak-MA as 351±67μmvs 319±59μm;minimum thickness 311±62μm vs 284±60μm;maximum thickness 389±78μm vs 352±66μm;and retina volume 26.4±6.0mmvs 23.6±3.7mm3,***: Leaking of microaneurysms on fluorescein angiography appears to cause focal thickening of retina,which can be measured with high-resolution ***,targeting leaking microaneursyms in diabetic retinopathy has the potential to reduce retinal thickening.

关键词： diabetic retinopathy microaneurysm retinal thickness OCT

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Role of wide-field autofluorescence imaging and scanning laser ophthalmoscopy in differentiation of choroidal pigmented lesions

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International Journal of Ophthalmology(English edition) 2014年第4期7卷 697-703页

作者： Lukas Reznicek Carmen stumpf Florian seidensticker Anselm Kampik aljoscha s Neubauer Marcus Kernt Department of Ophthalmology Ludwig Maximilians University Muenchen

·AIM:Toevaluatethe diagnostic properties of wide-field fundus autofluorescence(FAF) scanning laser ophthalmoscope(sLO) imaging for differentiating choroidal pigmented lesions.·METHODs: A consecutive series of 139 patients were included, 101 had established choroidal melanoma with13 untreated lesions and 98 treated with ***-eight had choroidal nevi. All patients underwent a full ophthalmological examination, undilated wide-field imaging, FAF and standardized Us examination. FAF images and imaging characteristics from sLO were correlated with the structural findings in the two patient groups.·REsULTs: Mean FAF intensity of melanomas was significantly lower than the FAF of choroidal nevi. Only 1out of 38 included eyes with nevi touched the optic disc compared to 31 out of 101 eyes with melanomas. In 18 out of 101 melanomas subretinal fluid was seen at the pigmented lesion compared to none seen in eyes with confirmed choroidal nevi. In 'green laser separation', a trend towards more mixed FAF appearance of melanomas compared to nevi was observed. The mean maximal and minimal transverse and longitudinal diameters of melanomas were significantly higher than those of nevi.·CONCLUsION: Wide-field sLO and FAF imaging may be an appropriate non-invasive diagnostic screening tool to differentiate benign from malign pigmented choroidal lesions.

关键词： imaging autofluorescence scanning laser ophthalmoscopy choroidal lesion melanoma

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Demographics, societal aging, and meat consumption in China

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Journal of Integrative Agriculture 2015年第6期14卷 995-1007页

作者： MIN shi BAI Jun-fei James seale Jr. Thomas wahl Institute of Development and Agricultural Economics Leibniz University Hannover College of Economics and Management China Agricultural University Department of Food and Resource Economics University of Florida Department of Agribusiness and Applied Economics North Dakota State University

Drawn on the data collected by surveying 1 340 urban households from six cities in China, this paper estimates the impacts of demographic structure and population aging on household meat consumption, by jointly considering meat consumed at home and away from home. Based on the trajectories of population, a simple simulation on meat demand trend in China is conducted subsequently. The results suggest： 1） Meat consumed away from home averagely accounts for near 30% of household total meat consumption in terms of quantity, so that its omission likely leads to a significant underestimate of total meat consumption and misunderstanding the driving forces; 2） population aging significantly and negatively affects per capita meat consumption, suggesting that the expected meat demand in China without considering population aging will be overestimated. The findings from this study have important implications for better understanding the relative issues on China＇s meat consumption under the situation of population aging.

关键词： capita household consumed income demographic jointly likely surveying estimates proportion

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玻璃体腔注射贝伐单抗治疗PDR黄斑水肿后患者的满意度和视力(英文)

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国际眼科杂志 2009年第9期9卷 1648-1651页

作者： Lala Ceklic slobodanka Latinovic aljoscha s Neubauer Marijana Malesevic 波黑萨拉热窝临床中心眼科塞尔维亚诺维萨德大学眼科诊所德国慕尼黑大学眼科

目的:增生性糖尿病性视网膜病播散性视网膜激光光凝后,用非选择性抗VEGF抑制剂贝伐单抗治疗糖尿病性黄斑水肿,调查患者自我评估的视功能及视力。方法:30例30眼增生性糖尿病性视网膜病伴持续性糖尿病性黄斑水肿连续病例,播散性视网膜激... 详细信息

目的:增生性糖尿病性视网膜病播散性视网膜激光光凝后,用非选择性抗VEGF抑制剂贝伐单抗治疗糖尿病性黄斑水肿,调查患者自我评估的视功能及视力。方法:30例30眼增生性糖尿病性视网膜病伴持续性糖尿病性黄斑水肿连续病例,播散性视网膜激光光凝后,1.25mg贝伐单抗0.05mL (Avastin)单剂量玻璃体腔注射治疗。对照组包括30例30眼增生性糖尿病性视网膜病,只接受播散性视网膜激光光凝。主要的调查结果包括snellen视力,眼底临床检查和患者自我用0-100分数值范围评价的视觉质量。结果:贝伐单抗组的平均基线视力为0.48±0.58 logMAR,对照组为0.61±0.78 (两组无显著差异)。6mo后,视力没有显著的变化,贝伐单抗组和对照组分别为0.33±0.41和0.52±0.68。临床检查显示黄斑水肿仅有一些改善趋势。患者用直观模拟标度尺主观评价视功能结果显示注射贝伐单抗6mo后由60.2±17.5改善至76.0±15.6 (Pstin)玻璃体腔注射作为播散性激光光凝的辅助治疗较单纯的激光治疗后患者满意度和自我评价的视力显著改善。患者视力在6mo后无明显变化。

关键词：增生性糖尿病性视网膜病视力自我评估贝伐单抗播散性视网膜激光光凝

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视网膜耳蜗脑微血管病并突发周边视野缺损及听力损失:susac综合征1例(英文)

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国际眼科杂志 2010年第2期10卷 222-224页

作者： Marcus Kernt aljoscha s Neubauer stephan Thurau Mi-chael W Ulbig 路德维希马克西米利安大学眼科

目的:报告1例25岁女性患susac综合征(ss),突发周边视野缺损及听力丧失。方法:报告1例25岁女性患者突发周边视野缺损及听力丧失,并记录视网膜超广角血管造影检查结果之间的相互关系以及所展现的视野缺损。结果:患者显现出ss特有的临床三... 详细信息

目的:报告1例25岁女性患susac综合征(ss),突发周边视野缺损及听力丧失。方法:报告1例25岁女性患者突发周边视野缺损及听力丧失,并记录视网膜超广角血管造影检查结果之间的相互关系以及所展现的视野缺损。结果:患者显现出ss特有的临床三联征。我们可以看出视网膜超广角血管造影检查结果和视野缺损之间的一些相互关系。结论:经证明超广角血管造影术是一个在临床治疗中检测和追踪ss周围病变的有价值的工具。

关键词： susac综合征广角血管造影术欧宝全景照相系统眼底成像视网膜微血管病

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复杂性眼外伤治疗(英文)

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国际眼科杂志 2011年第5期11卷 767-768页

作者： Lala Ceklic slobodanka Latinovic aljoscha s. Neubauer Djoko Obucina Bobana Petrovic 东萨拉热窝眼科临床中心波黑东萨拉热窝 Ludvig Maximillian大学眼科诊所德国慕尼黑

本文报告开放性眼球损伤1例,鱼钩卡在角膜和虹膜处。由于这种复杂眼外伤可能导致非常危险的并发症,并且严重影响视觉功能。现将处理方法总结如下:首先,取出异物,缝合眼球;其次,抗感染治疗;最后,实施白内障手术以便视力恢复。

关键词：眼外伤前房异物外伤性白内障

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