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The purpose of this study was to investigate the key factors that affect the implementation of collaborative planning, forecasting, and replenishment (CPFR). A single case study method was adopted, examining a critical case in the South African grocery retail sector. Semi-structured interviews were conducted to collect data. The study confirmed five of the six key factors affecting CPFR implementation that have been identified in the literature. Two new key factors, business understanding and a common goal, were identified. The study also determined the framework that the focal firm used to implement CPFR. The findings aid supply chain managers in understanding and leveraging the key factors that affect the successful implementation of CPFR. The framework can be used for benchmarking and guiding managers through the process of implementing CPFR. Die doel van hierdie studie was om die belangrike faktore wat die implementering van gesamentlike beplanning, vooruitskatting, en aanvulling (GBVA) beïnvloed te ondersoek. 'n Enkele gevallestudie metode was gebruik om 'n kritieke geval binne die Suid-Afrikaanse kruideniersware kleinhandelsektor te ondersoek. Semi-gestruktureerde onderhoude was uitgevoer om data in te samel. Die studie het vyf van die ses belangrikste faktore bevestig wat GBVA implementering beïnvloed, soos wat vervat is in die literatuur. Twee nuwe sleutel faktore, besigheidsbegrip en 'n gemeenskaplike doel, was geïdentifiseer. Die studie het ook die raamwerk bepaal wat die firma gebruik het om GBVA te implementeer. Die studie bemagtig voorsieningskettingbestuurders om die belangrikste faktore wat die suksesvolle implementering van GBVA beïnvloed te verstaan en te benut. Die raamwerk kan help om 'n normtoets te stel en bestuurders te lei deur die proses van die GBVA implementering.

Continuous welded rail (CWR) is a fundamental component of any modern track structure and has several advantages over former types of rail joining processes. The reduction in maintenance and related costs has become the most attractive property of CWR although careful monitoring and maintenance of CWR is essential to ensure safe train operations. Management of the stress-free temperature (SFT) of any section of CWR in order to prevent rail breaks and lateral buckling that could lead to derailments is a vital duty of the track maintenance team. Variations in the SFT are influenced by a number of external factors. This paper describes experimental field and laboratory tests carried out to investigate to what extent the fastening strength influences the variation in SFT in CWR track on Fist fastenings and two types of pads. The research established a nonlinear relationship between clamping force and rail movement through the fasteners as well as a strongly linear relationship between clamping force and the variation in SFT. It is also demonstrated that although the friction coefficient of the pad has an influence on rail movement through the fastener, the primary factor influencing SFT variations is the clip force. This paper concludes by quantifying the relationship between clamping force and the expected variation in SFT with clear guidelines on the management of the SFT in CWR.

An efficient synthesis of the neuramidase inhibitor A-315675 is reported. The fully functionalized pyrrolidine core of the target is assembled in one pot via an exo-selective asymmetric [C+NC+CC] coupling reaction.

While several therapeutic options exist, the need for more effective, safe, and convenient treatment for a variety of autoimmune diseases persists. Targeting the Janus tyrosine kinases (JAKs), which play essential roles in cell signaling responses and can contribute to aberrant immune function associated with disease, has emerged as a novel and attractive approach for the development of new autoimmune disease therapies. We screened our compound library against JAK3, a key signaling kinase in immune cells, and identified multiple scaffolds showing good inhibitory activity for this kinase. A particular scaffold of interest, the 1H-pyrrolo[2,3-b]pyridine series (7-azaindoles), was selected for further optimization in part on the basis of binding affinity (Ki) as well as on the basis of cellular potency. Optimization of this chemical series led to the identification of VX-509 (decernotinib), a novel, potent, and selective JAK3 inhibitor, which demonstrates good efficacy in vivo in the rat host versus graft model (HvG). On the basis of these findings, it appears that VX-509 offers potential for the treatment of a variety of autoimmune diseases.

In our effort to develop agents for the treatment of influenza, a phenotypic screening approach utilizing a cell protection assay identified a series of azaindole based inhibitors of the cap-snatching function of the PB2 subunit of the influenza A viral polymerase complex. Using a bDNA viral replication assay (Wagaman, P. C., Leong, M. A., and Simmen, K. A. Development of a novel influenza A antiviral assay. J. Virol. Methods 2002, 105, 105-114) in cells as a direct measure of antiviral activity, we discovered a set of cyclohexyl carboxylic acid analogues, highlighted by VX-787 (2). Compound 2 shows strong potency versus multiple influenza A strains, including pandemic 2009 H1N1 and avian H5N1 flu strains, and shows an efficacy profile in a mouse influenza model even when treatment was administered 48 h after infection. Compound 2 represents a first-in-class, orally bioavailable, novel compound that offers potential for the treatment of both pandemic and seasonal influenza and has a distinct advantage over the current standard of care treatments including potency, efficacy, and extended treatment window.