Supramolecular Assembly of Aminoethylene‐Lipopeptide PMO Conjugates into RNA Splice‐Switching Nanomicelles

Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile.     

PMO managers' self-determined participation in a purposeful virtual community-of-practice

Communities-of-practice (CoPs) have received significant attention within a variety of literatures but we remain largely ignorant of the potential of purposefully-created CoPs in global organisations. In this context, the challenge is likely to be convincing ‘masters’ (Wenger, 1998) on the merits of joining the conversation on practice at a distance, thus making the willingness for exchange a key to the quality and longevity of the community. We posed the question “Why would busy, dispersed, knowledgeable professionals want to join and participate in a deliberately-organised CoP?” Our 2-year collaborative action study allowed us to observe the CoP and its membership at close range. We conclude that autonomy, competence and belonging underscore participation, co-production and diffusion of innovative problem-solving and practice beyond the CoP. The study will inform organisations contemplating similar interventions and also serves as a basis for further investigation and theory building on organized CoPs by the research community.     

PMO对GCr15轴承钢连铸坯中MnS夹杂物的影响

为了研究PMO对GCr15轴承钢连铸坯中MnS夹杂物的影响,首先采用自动扫描电镜(Aspex Explorer)分析脉冲磁致振荡(Pulse Magneto-Oscillation,PMO)技术对钢中MnS类夹杂物组成和形貌的影响,然后利用电子探针测量固液界面前沿的元素含量,并在此基础上,计算了PMO处理后MnS析出温度变化。结果表明,PMO处理促进了内弧1/4、中心和外弧1/4处的大于8 μm的MnS夹杂物数量百分比的降低;PMO处理后固液界面前沿S元素质量分数在试样凝固50%和70%处分别降低60%和36%,而Mn元素含量变化不大;同时,PMO处理可降低MnS夹杂物的析出温度。     

跨区域汽车4S店项目群管理的案例研究

在多项目环境下，传统的专注于单一项目的项目管理理论面临着很多挑战，如项目与组织战略存在脱节，资源无法在众多项目中得到合理分配等。因此，以信息技术为依托的项目群管理理论得到了较大发展。文章在简要介绍项目群管理理论的基础上，根据作者亲历的汽车4S店项目群建设，从实践角度对项目群管理理论进行研究，并在此基础上总结出一些经验。     

脉冲磁致振荡(PMO)凝固均质化技术在特殊钢中的应用

摘要：脉冲磁致振荡（PMO）凝固均质化技术是由上海大学先进凝固技术中心基于外场下金属凝固原理提出的原创技术。经过15年的研发,该技术已成功走向工业应用。介绍了PMO技术的原理以及在GCr15轴承钢、20CrMnTi齿轮钢和锚链钢等特殊钢工业生产中的应用情况。工业应用表明,PMO技术不仅可以显著增加铸坯等轴晶比例,改善铸坯偏析,而且可以提高铸坯拉速,并放宽对中间包过热度控制的要求。     

铁路多项目管理及其组织模式的研究应用

简述多项目管理理论,针对铁路扩大建设规模,处于建设高峰期的现状,引入多项目管理方法。分析铁路多项目管理的组织需求,提出一种新的适应铁路建设项目管理的组织模式——PMO多项目管理组织模式,并对其职能、设置和运行中需要注意的问题进行了详细的论述。     

企业多项目管理模式的探讨

介绍了多项目管理框架定义的四个基本分工层次：高层领导团队,项目总的负责人,计划制定部门,项目团队;并分析实施多项目管理面临的问题,引入PMO工具,有效地解决多项目管理的问题,不但摆脱了直线职能型组织应对多项目管理力不从心的尴尬局面,而且还避免了矩阵型组织徘徊于“职能”和“项目”之间的两难境地。     

Why and how do project management offices change? A structural analysis approach

The growing popularity of Project Management Offices (PMOs) as organizational structures is grounded in the assumption they support more efficient and effective project management for better strategy implementation. However, research emphasizes they fail to deliver expected value: their unstable nature precludes the delivery of long-term benefits. This is compounded by the absence of a theory of PMO change and adaptation. Recent research, taking a co-evolution lens rooted in evolutionary theory, suggests that PMOs should be studied in relation to the broader organizational context, in order to better capture the dynamic interplay and fit between them. In this study, taking a routine perspective as micro-foundation and unit of analysis, we focus on the co-evolution between PMO and Project Portfolio Management (PfM) as organizational capability for six case studies. A structural analysis of the relational routines' system between PMO, PfM and the Organizational context allow us to unveil dynamics at stake, i.e. why and how changes occur, as well as eigen behaviors and the changing states of various routines elements (influential, mediating, dependent or not-influential). This study makes five contributions. We show that: 1) PMO and PfM can be conceptualized as collections of routines, 2) PMO and PfM co-evolve over time to adapt to organizational context influence, 3) the co-evolution of a routines' system, abstracted as a non-trivial machine, exhibits an eigen behavior, 4) applying a structural analysis approach allows to simulate the dynamics of a routines' system and to unveil the role of key routine elements and 5) eigen values of routines' systems allow to characterize their eigen behavior.     

应用PMO提高连铸坯生产拉速及成分均匀性

为了实现电炉厂提产增效的目标,研究了脉冲磁致振荡(PMO)在提高铸坯生产拉速中的应用潜能。结果表明,优化PMO处理参数可以适应生产拉速提高的要求,并改善铸坯的中心偏析和宏观偏析。当连铸拉速提至1.05 m/min,PMO脉冲频率为1.16K_f Hz,峰值电压为1.00K_iV处理参数(K_f和K_i分别为仪器的放电频率和电压峰值)时, 铸坯横断面碳偏析指数可控制在1±0.05内;当连铸拉速提至1.15 m/min,PMO脉冲频率为1.28K_fHz,峰值电压为1.00K_iV处理参数时,铸坯横断面碳偏析指数可控制在1±0.07内。试验证明,在高拉速条件下通过保证单位时间内对钢液施加的脉冲能量可以使连铸坯质量得到有效改善。