| 1. |
- Garmabaki, Amir Soleimani, et al.
(författare)
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The Optimal Time of New Generation Product in the Market
- 2012
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Ingår i: Communications in Dependability and Quality Management. - 1450-7196. ; 15:1, s. 123-137
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Tidskriftsartikel (refereegranskat)abstract
- Most product development activities are aimed at improving existing products by successive generation policy. The launch of a new product is a phase of development that commands a large commitment of time, money, and managerial resources. Determination of optimal introduction time is especially critical for high-technology products, where the introduction of each successive generation of a product requires the firm to explicitly consider its impact on the demand for preceding generations. Each generation has unique expectations, experiences, generational history, lifestyles, values, and demographics that influence behavior of potential buyers. Accordingly, many companies are reaching out to multi-generational consumers and trying to understand and gain the attention of these diverse buyers. The timing decision depends on whether companies invest more time for product design or push the product to market before maturity. The study identifies attributes such as Customer's Adoption Indicator and Cost that affect the introduction time of new generation. To trade-off between two decision factors, multi-attribute utility theory (MAUT) is applied in our decision space. We examine the case where a firm introduces successive generations of a durable product for which demand is characterized by an innovation diffusion process. Empirical implications of the proposed model have been validated on data collected from two industries (Semiconductor Industry DRAM shipments and IBM Mainframe Industry (USA)).
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| 2. |
- Reddy, B. K. Kishore, et al.
(författare)
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Assessment of Mycobacterium tuberculosis Pantothenate Kinase Vulnerability through Target Knockdown and Mechanistically Diverse Inhibitors
- 2014
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 58:6, s. 3312-3326
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Tidskriftsartikel (refereegranskat)abstract
- Pantothenate kinase (PanK) catalyzes the phosphorylation of pantothenate, the first committed and rate-limiting step toward coenzyme A (CoA) biosynthesis. In our earlier reports, we had established that the type I isoform encoded by the coaA gene is an essential pantothenate kinase in Mycobacterium tuberculosis, and this vital information was then exploited to screen large libraries for identification of mechanistically different classes of PanK inhibitors. The present report summarizes the synthesis and expansion efforts to understand the structure-activity relationships leading to the optimization of enzyme inhibition along with antimycobacterial activity. Additionally, we report the progression of two distinct classes of inhibitors, the triazoles, which are ATP competitors, and the biaryl acetic acids, with a mixed mode of inhibition. Cocrystallization studies provided evidence of these inhibitors binding to the enzyme. This was further substantiated with the biaryl acids having MIC against the wild-type M. tuberculosis strain and the subsequent establishment of a target link with an upshift in MIC in a strain overexpressing PanK. On the other hand, the ATP competitors had cellular activity only in a M. tuberculosis knockdown strain with reduced PanK expression levels. Additionally, in vitro and in vivo survival kinetic studies performed with a M. tuberculosis PanK (MtPanK) knockdown strain indicated that the target levels have to be significantly reduced to bring in growth inhibition. The dual approaches employed here thus established the poor vulnerability of PanK in M. tuberculosis.
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