Statistical Inference in a Two-Compartment Model for Hematopoiesis

We present a method for parameter estimation in a two-compartment hidden Markov model of the first two stages of hematopoiesis. Hematopoiesis is the specialization of stem cells into mature blood cells. As stem cells are not distinguishable in bone marrow, little is known about their behavior, although it is known that they have the ability to self-renew or to differentiate to more specialized (progenitor) cells. We observe progenitor cells in samples of bone marrow taken from hybrid cats whose cells contain a natural binary marker. With data consisting of the changing proportions of this binary marker over time from several cats, estimates for stem cell self-renewal and differentiation parameters are obtained using an estimating equations approach.     

Kinetics of Veratryl Alcohol Oxidation by Lignin Peroxidase and in situ Generated Hydrogen Peroxide in an Electrochemical Reactor

The cathodic reduction of oxygen to hydrogen peroxide, the current efficiency for the production of H₂O₂ and the oxidation of veratryl alcohol with an in situ generated hydrogen peroxide‐lignin peroxidase complex were studied in this paper. The complex was prepared by utilizing a novel preparation technique in an electrochemical reactor. The oxidation of veratryl alcohol (VA; 3,4‐dimethoxybenzyl alcohol) was carried out with or without lignin peroxidase under an electric field. The redox properties of veratryl alcohol on a carbon electrode in the presence of lignin peroxidase have been investigated using cyclic voltammetry. The kinetics of veratryl alcohol oxidation in an electrochemical reactor were compared to the oxidation when hydrogen peroxide was supplied externally. Further, the oxidation of veratryl alcohol by lignin peroxidase was optimized in terms of enzyme dosage, pH, and electrical potential. The novel electroenzymatic method was found to be effective using in situ generated hydrogen peroxide for the oxidation of veratryl alcohol by lignin peroxidase.     

5-酮基-D-葡萄糖酸发酵生产的工艺条件优化

葡萄糖酸氧化杆菌可将葡萄糖转化为5-酮基-D-葡萄糖酸(5-KGA),而5-KGA是重要食品添加剂L(+)-酒石酸的合成前体。为提高5-KGA产量及其对葡萄糖的转化率,对5-KGA发酵生产的工艺条件进行优化。在摇瓶水平最适的培养基和培养条件下,5-KGA最高产量为19.7 g/L,较优化前提高43.8%。在5 L发酵罐上控制恒定pH值5.5、溶氧浓度15%条件下,5-KGA产量达到46.0 g/L,较摇瓶最高产量提高1.3倍,应用葡萄糖流加工艺,5-KGA最高产量达到75.5 g/L,转化率超过70%,与已见报道的最高水平相比提高了32.0%,为实现微生物发酵生产5-KGA、进而合成L(+)-酒石酸的工业化提供了切实有效的途径。     

酿酒葡萄品质评价及其对气象条件的响应

根据2004～2005年我国北方6省酿酒葡萄主要产区葡萄取样和宁夏芦花台园艺场田间试验葡萄化验结果,运用层次分析方法（AHP）对酿酒葡萄主要品质因子总糖、糖酸比pH、单宁进行综合评价,运用主成分分析方法和因子分析法研究影响每个地区酿酒葡萄综合品质的主要气象因子和影响时段。结果表明：2004～2005年贺兰山东麓的御马、玉泉营、广夏三基地、贺东在庄园;河西走廊的高台、武威;新疆石河子酿酒葡萄品质优良,渤海湾的烟台、蓬莱、昌藜等地酿酒葡萄品质表现一般。酿酒葡萄综合品质主要受果实着色期、全生育期和7～8月的降水量和水热系数的影响,其中降水量起主导作用。果实着色期气温日较差和全生育期平均相对湿度对酿酒葡萄综合品质的形成也有重要影响,影响相对较小的是果实着色期的最低气温。采样地区的光照、温度等气象条件基本适宜酿酒葡萄品质形成,对优质酿酒葡萄形成没有大的限制作用。     

Industrial process proteomics: alfalfa protein patterns during wet fractionation processing

A proteome reference map of major soluble proteins from Medicago sativa (alfalfa) leaves and stems has been established for the first time. Among 195 spots analyzed by mass spectrometry and N-terminal Edman sequencing, 117 spots were unambiguously identified, representing 87 different proteins. Of these 87 proteins, 13 proteins were directly identified from the partial genome of Medicago sativa, 30 from expressed sequenced tags (ESTs) of the model legume Medicago truncatula and 44 from closely relative species by a cross-species protein identification method. The proteome map of Medicago sativa was then set as a reference to study the major high protein content products that are generated during the wet fractionation process of alfalfa green biomass. Using two-dimensional electrophoresis, we studied the variation of the protein patterns at different steps of the industrial-scale process. We clearly show that the process induces significant changes including chemical modifications, proteolytic events, and heat-shock protein responses. Strikingly, a certain level of cellular regulation is conserved during biomass processing, as exemplified by the induction of some heat shock proteins. Finally, all the results obtained in this proteomic study may help to identify novel products and to improve process designs in alfalfa biomass plants.     

Pilot study to assess the validity of the single assessment process as a screening tool for dental treatment needs in older people

Objective: To assess the feasibility of using a questionnaire‐based needs assessment tool (D‐E‐N‐T‐A‐L) to screen for dental treatment need as part of the single assessment process (SAP) for older people in Sheffield. Materials and methods: Test validation study comparing questionnaire‐assessed and normative need in two consecutive samples of older adults: 48 living at home in the transition phase of older age and 29 frail older adults living in care homes. Each answered the six D‐E‐N‐T‐A‐L questions as part of SAP and a dental examination was carried out within 2 weeks in participants’ homes. Question‐defined need was then compared to the normative need. Results: Questionnaire‐defined and normative need were high in both the transitional group (83% and 90% respectively) and the frail group (83% and 62%). These high levels of need meant that the sensitivity and positive predictive values of D‐E‐N‐T‐A‐L were high, but the specificity and negative predictive values were low. Conclusion: The high levels of need in these patient groups suggests that preliminary questionnaire‐based screening is an unnecessary step. A clinical examination of all older people undergoing SAP may be necessary. Further research may be warranted on the use of questionnaires to assess dental treatment needs among people with different attendance patterns.     

Lineages-through-time plots of neutral models for speciation

Drawing inferences about macroevolutionary processes from phylogenetic trees is a fundamental challenge in evolutionary biology. Understanding stochastic models for speciation is an essential step in solving this challenge. We consider a neutral class of stochastic models for speciation, the constant rate birth-death process. For trees with n extant species - which might be derived from bigger trees via random taxon sampling - we calculate the expected time of the kth speciation event (k=1,...,n-1). Further, for a tree with n extant species, we calculate the density and expectation for the number of lineages at any time between the origin of the process and the present. With the developed methods, expected lineages-through-time (LTT) plots can be drawn analytically. The effect of random taxon sampling on LTT plots is discussed.     

Continuous bioprocessing: The real thing this time?: 10th Annual bioProcessUK Conference,December 3–4, 2013, London,UK

The Annual bioProcessUK Conference has acted as the key networking event for bioprocess scientists and engineers in the UK for the past 10 years. The following article is a report from the sessions that focused on continuous bioprocessing during the 10^th Annual bioProcessUK Conference (London, December 2013). These sessions were organized by the ‘EPSRC Centre for Innovative Manufacturing in Emergent Macromolecular Therapies’ hosted at University College London. A plenary lecture and workshop provided a forum for participants to debate topical issues in roundtable discussions with industry and academic experts from institutions such as Genzyme, Janssen, Novo Nordisk, Pfizer, Merck, GE Healthcare and University College London. The aim of these particular sessions was to understand better the challenges and opportunities for continuous bioprocessing in the bioprocessing sector.     

狂犬病疫苗蔗糖密度梯度离心纯化工艺开发

目的:开发冻干人用狂犬病疫苗(鸡胚成纤维细胞)的连续流蔗糖密度梯度离心纯化工艺。方法:分别比较两种不同初始蔗糖浓度和不同上样速度对纯化效果的影响,初步确定纯化工艺;通过多批次实验确定样品收集范围;比较不同浓缩倍数条件下杂质去除和抗原回收情况,确定合适的收获液浓缩比例;比较不同批次样品纯化后的杂质去除率和重复性,判定本纯化工艺的稳定性。结果:选取60%作为初始蔗糖浓度,在上样速度为150～200ml/min时,可以有效地对10倍浓缩的病毒收获液进行纯化;卵清蛋白、牛血清白蛋白和庆大霉素去除率分别达到99%,95%和95%,且工艺具有极好的稳定性。结论:开发的连续流蔗糖密度梯度离心技术可以作为冻干人用狂犬病疫苗(鸡胚成纤维细胞)的产业化纯化工艺。