This paper describes a model which has been developed to direct and generate productivity improvement in a group of manufacturing companies. The companies are of all sizes including Small and Medium ...Enterprises (SMEs) and form a cross-section of industries and abilities with regard to manufacturing. There is a wide range of manufacturing efficiency improvement methods available to the companies, such as Just in Time (JIT), or a range of lean manufacturing tools. The selection of appropriate tools for manufacturing improvement, together with their applicability, incorporation and acceptance within operations is a major problem for many companies. A methodology has therefore been developed which consists of three clearly defined steps, starting with a Productivity Needs Analysis (PNA), which gives an overview of the current manufacturing condition of the company, identifies the key productivity measures for the plant and forms the basis for a detailed study of production efficiency. The plant processes and problems are defined and are associated with the appropriate tools and metrics in a Manufacturing Needs Analysis (MNA), which generates an initial 1-year improvement plan for a particular manufacturing unit. The output from the procedure is obtained as a numerical ranking. In order to ensure that the tools which are found to be efficacious are fully embedded within the company, the PNA and MNA are combined with a Training Needs Analysis (TNA). The paper describes the approach and the results obtained from 15 companies plus an identified exemplar, Nissan Motor Manufacturing UK Ltd. (NMUK).
Infection of macaques with chimeric viruses based on SIVMAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic ...strategies against AIDS. Unfortunately, only a few SHIVs are currently available. Furthermore, their generation has required extensive adaptation of the HIV-1 Env sequences in macaques so they may not accurately represent HIV-1 Env proteins circulating in humans, potentially limiting their translational utility. We developed a strategy for generating large numbers of SHIV constructs expressing Env proteins from newly transmitted HIV-1 strains. By inoculating macaques with cocktails of multiple SHIV variants, we selected SHIVs that can replicate and cause AIDS-like disease in immunologically intact rhesus macaques without requiring animal-to-animal passage. One of these SHIVs could be transmitted mucosally. We demonstrate the utility of the SHIVs generated by this method for evaluating neutralizing antibody administration as a protection against mucosal SHIV challenge.
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•Large numbers of SIVMAC expressing transmitted HIV-1 Env proteins (SHIVs) were generated•SHIVs that replicate best in macaques were selected after inoculation with virus pools•Selected SHIVs cause AIDS without requiring adaptation in animals•A broadly neutralizing antibody protects against mucosal challenge with a selected SHIV
SIVMAC expressing HIV-1 envelopes (SHIVs) are used to model AIDS in monkeys, but the available SHIVs are extensively adapted. Del Prete et al. generated SHIVs expressing newly transmitted HIV-1 envelope proteins and screened virus pools in monkeys to select unadapted SHIVs that cause AIDS. Their utility for immunoprophylactic studies is demonstrated.
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