On a Continuous Branching Process and Birth-Death and Immigration Models for Testing the Efficacy of Some Control Programmes for AIDS

The present communication is an attempt to describe the mode of propagation of AIDS epidemic and its control programme using a branching process as well as a birth-death and immigration model. A comparison of the project of AIDS control programme on the basis of its propagation by a continuous branching process model with that of a linear birth and death process with immigration shows a remarkable contrast. Branching process model shows that it is possible to control the propagation of the disease by suitably increasing the detection rate and lowering the infection rate. However, the propagation of AIDS models by birth and death Process with or without immigration shows that it is increasingly difficult to control the invasion of AIDS merely by controlling the birth, death and immigration parameters.     

厌氧氨氧化组合脱氮工艺研究进展

厌氧氨氧化工艺是一项高效、低耗的生物脱氮工艺,但受限于底物类型、硝氮积累等问题,其在主流应用中仍然面临一些挑战。近些年来,针对上述问题,厌氧氨氧化组合工艺得到了广泛关注。通过对近年来所开发的厌氧氨氧化组合工艺,从工艺原理、优缺点、影响因素、工艺拓展性及其在推广应用中存在的关键瓶颈等角度进行探讨,并结合课题组相关工作,展望了厌氧氨氧化组合工艺在城市生活污水处理中的发展前景。     

Meeting report: Third Franco-Japanese developmental biology meeting “New Frontiers in developmental biology: Celebrating the diversity of life”

The French and Japanese Developmental Biology Societies, teaming up with Human Frontier Science Program, were eager to meet back in person in November 2022 in the lovely city of Strasbourg. Top scientists in the developmental biology field from France and Japan, but also from United States, United Kingdom, Switzerland or Germany shared their exciting science during the 4 days of this meeting. Core fields of developmental biology such as morphogenesis, patterning, cell identity, and cell state transition, notably at the single cell level, were well represented, and a diversity of experimental models, including plants, animals, and other exotic organisms, as well as some in vitro cellular models, were covered. This event also extended the scope of classic scientific gatherings for two reasons. First the involvement of artists during the preparation of the event and on site. Second, part of the meeting was open for the general public through a series of outreach events, including a music and video presentation through projection mapping at Rohan palace, as well as public lectures.     

The roles of a process development group in biopharmaceutical process startup

The transfer of processes for biotherapeutic products into finalmanufacturing facilities was frequently problematic during the 1980's and early 1990's, resulting in costly delays to licensure(Pisano 1997). While plant startups for this class of products can become chaotic affairs, this is not an inherent or intrinsic feature. Major classes of process startup problems have been identified andmechanisms have been developed to reduce their likelihood of occurrence. These classes of process startup problems and resolution mechanisms are the major topic of this article. With proper planning and sufficient staffing, the probably of a smooth process startup for a biopharmaceutical product can be very high – i.e., successful process performance will often beachieved within the first two full-scale process lots in the plant. The primary focus of this article is the role of the Process Development Group in helping to assure this high probability of success.     

Process development and intensification for enhanced production of Bacillus lipopeptides

The growing interest in Bacillus lipopeptides for high-value applications has driven process design, development and optimization for enhanced lipopeptide production. Traditional optimization approaches have been directed towards improving the overall titres by modification of media components and environmental parameters, almost exclusively in submerged cultures. Carbon and nitrogen sources, trace elements and oxygen availability have all been demonstrated to exhibit significant influences on lipopeptide yield, productivity and selectivity. This insight into process-linked kinetics, especially selectivity, has led to the introduction of novel process intensification and integration strategies which further promote process efficiency, and which include foam fractionation, inverse fluidization, rotating disc contacting and microfiltration with recycle. These strategies have not only transformed the production capabilities, but have also successfully integrated upstream production with downstream purification through cell retention and in situ product removal. This review analyses and critically discusses the impact of process conditions and process optimization strategies for improving lipopeptide production kinetics, specifically highlighting the emerging trend of process intensification and integration strategies and further, proposes a heuristic route to enhance lipopeptide production.     

On Second Order Neighbourhood Analysis of Mapped Point Patterns

Getis and Franklin (1987), introduced a technique based on second order methods, called second order neighbourhood method, which is used to quantify clustering at various spatial scales. Variants of this method are introduced for testing whether a spatial point pattern is consistent with the hypothesis of a Poisson process. These variants are applied to point location data for a sample of Ponderosa pine (Pinus ponderosa) trees.     

基于医院信息系统开展医疗质量控制的实践

依托医院现有信息技术系统,以冠脉介入手术为例,经与临床专家沟通确定冠脉介入手术医疗质量监控指标十余项。通过收集、整理、分析近2年数据,根据数据分析结果开展相关医疗质量控制管理工作,并收到良好的工作效果。     

A Single Compartment Quantal Response Model with an Inspection Process

In a single compartment quantal response model, besides the input and release processes, an inspection process, assumed to be independent of the input and release processes, is considered. Each time when a release occurs, we assume the amount of release is randomly proportional to the amount present and the proportional rates form a sequence of independent and identically distributed random variables with support on [0, 1]. The input policy we consider is a modification of (s, S) input policy in the inventory model. More precisely, let 0 ≦s₂ ≦s₁ ≦s ≦ S, if after a release, the amount of the drug in subject's body is less than a level s₂ which is small enough, then there will be an input immediately with probability 1 — p and no more inputs thereafter with probability p, also there will be an input immediately if the dose level is in the interval [s₂, s₁). If the dose level is in the interval [s₁, s) there will be no input unless the inspector arrives. On the other hand, if the dose level is greater than or equal to s, then there will be no input. We consider a stochastic model as described above, and obtain the expressions for some quantities of interest. A Monte Carlo study has also been carried out to demonstrate some behaviors of our quantal response process.     

Implementation of chemometrics,design of experiments,and neural network analysis for prior process knowledge assessment,failure modes and effect analysis,scale-down model development,and process characterization for a chromatographic purification of Teriparatide

Process understanding and characterization forms the foundation, ensuring consistent and robust biologics manufacturing process. Using appropriate modeling tools and machine learning approaches, the process data can be monitored in real time to avoid manufacturing risks. In this article, we have outlined an approach toward implementation of chemometrics and machine learning tools (neural network analysis) to model and predict the behavior of a mixed-mode chromatography step for a biosimilar (Teriparatide) as a case study. The process development data and process knowledge was assimilated into a prior process knowledge assessment using chemometrics tools to derive important parameters critical to performance indicators (i.e., potential quality and process attributes) and to establish the severity ranking for the FMEA analysis. The characterization data of the chromatographic operation are presented alongwith the determination of the critical, key and non- key process parameters, set points, operating, process acceptance and characterized ranges. The scale-down model establishment was assessed using traditional approaches and novel approaches like batch evolution model and neural network analysis. The batch evolution model was further used to demonstrate batch monitoring through direct chromatographic data, thus demonstrating its application for continuos process verification. Assimilation of process knowledge through a structured data acquisition approach, built-in from process development to continuous process verification was demonstrated to result in a data analytics driven model that can be coupled with machine learning tools for real time process monitoring. We recommend application of these approaches with the FDA guidance on stage wise process development and validation to reduce manufacturing risks.     

造林气候调节效应及其影响机理研究进展

造林及人工林生长吸收并固定二氧化碳(CO₂),其"幼龄效应"使得全球中、高纬度新造林的CO₂吸收超过天然林,被认为是减缓全球变暖、控制升温2℃目标的一个关键战略,亦是生态保护修复和林业可持续发展并举的一个重要措施。我国人工林保有面积居全球首位,占林地面积的36%,近几十年造林为全球变绿的贡献超过10%。造林改变地表生物地球化学和生物物理过程从而影响温度、降水、成云、风等,在不同气候带、不同区域呈现差异性气候调节效应,取决于温室气体、辐射能量、水汽收支之间的平衡结果。分析了国际、国内在应对气候变化活动中对于造林的急迫需求,综述了造林气候调节效应的研究进展,以及产生这种效应的生物地球化学和生物物理机理,总结了当前研究中亟待深入探索的内容,并展望了未来造林仍需深入开展系统地生物地球化学和生物物理机理研究,推动可持续地人工林管理、恢复具有完整结构的森林、促进多重生态系统服务的协同。     

Process intensification for cytochrome P450 BM3-catalyzed oxy-functionalization of dodecanoic acid

Selective oxy-functionalization of nonactivated C-H bonds is a long-standing “dream reaction” of organic synthesis for which chemical methodology is not well developed. Mono-oxygenase enzymes are promising catalysts for such oxy-functionalization to establish. Limitation on their applicability arises from low reaction output. Here, we showed an integrated approach of process engineering to the intensification of the cytochrome P450 BM3-catalyzed hydroxylation of dodecanoic acid (C12:0). Using P450 BM3 together with glucose dehydrogenase for regeneration of nicotinamide adenine dinucleotide phosphate (NADPH), we compared soluble and co-immobilized enzymes in O₂-gassed and pH-controlled conversions at high final substrate concentrations (≥40mM). We identified the main engineering parameters of process output (i.e., O₂ supply; mixing correlated with immobilized enzyme stability; foam control correlated with product isolation; substrate solubilization) and succeeded in disentangling their complex interrelationship for systematic process optimization. Running the reaction at O₂-limited conditions at up to 500-ml scale (10% dimethyl sulfoxide; silicone antifoam), we developed a substrate feeding strategy based on O₂ feedback control. Thus, we achieved high reaction rates of 1.86g·L⁻¹·hr⁻¹ and near complete conversion (≥90%) of 80mM (16g/L) C12:0 with good selectivity (≤5% overoxidation). We showed that “uncoupled reaction” of the P450 BM3 (~95% utilization of NADPH and O₂ not leading to hydroxylation) with the C12:0 hydroxylated product limited the process efficiency at high product concentration. Hydroxylated product (~7g; ≥92% purity) was recovered from 500ml reaction in 82% yield using ethyl-acetate extraction. Collectively, these results demonstrate key engineering parameters for the biocatalytic oxy-functionalization and show their integration into a coherent strategy for process intensification.