Is the Make-Buy Decision Process a Core Competence?

Many of today's products are so complex that no single company has all the necessary knowledge about either the product or the required processes to completely design and manufacture them in-house. As a result, most companies are dependent on others for crucial elements of their corporate well-being. Typically, however, companies have some choice as to whom they become dependent upon and for what sorts of skills and competences. That is, although few companies can "do it all," most have significant influence over the strategic choice of corporate identity and what businesses to be in. What is the range of choices they face? How are different companies making those choices? Can we make sense of the variety of decisions we can observe now in different industries or different parts of the world? What are the skills that companies must retain? In this paper we address the challenge of making these choices rationally. We give examples in which similar companies, facing similar choices, select make/buy patterns in very different ways, resulting in very different patterns of interdependencies along companies' supply chains. These choices are not restricted to skills related to the product, but include choices related to key design and manufacturing issues. To make sense of these differences, we propose a framework that ties together the following engineering and management concepts into one coherent view: 1) core competencies 2) the product development process 3) systems engineering 4) product architecture and modularity, and 5) supply chain design.ONR and various MIT programs including Leaders for Manufacturing, International Motor Vehicle Program, Industrial Performance Center, Japan Program, International Center for Management of Technology

Agile Manufacturing and Customer- Supplier Relations in the Auto and Aircraft Industries

Presentation on agile manufacturing and customer-supplier relations in auto and aircraft industrie

Mapping the epithelial-cell-binding domain of the Aggregatibacter actinomycetemcomitans autotransporter adhesin Aae

The Gram-negative periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) binds selectively to buccal epithelial cells (BECs) of human and Old World primates by means of the outer-membrane autotransporter protein Aae. We speculated that the exposed N-terminal portion of the passenger domain of Aae would mediate binding to BECs. By using a series of plasmids that express full-length or truncated Aae proteins in Escherichia coli, we found that the BEC-binding domain of Aae was located in the N-terminal surface-exposed region of the protein, specifically in the region spanning amino acids 201–284 just upstream of the repeat region within the passenger domain. Peptides corresponding to amino acids 201–221, 222–238 and 201–240 were synthesized and tested for their ability to reduce Aae-mediated binding to BECs based on results obtained with truncated Aae proteins expressed in E. coli. BEC-binding of E. coli expressing Aae was reduced by as much as 50 % by pre-treatment of BECs with a 40-mer peptide (201–240; P40). Aae was also shown to mediate binding to cultured human epithelial keratinocytes (TW2.6), OBA9 and TERT, and endothelial (HUVEC) cells. Pre-treatment of epithelial cells with P40 resulted in a dose-dependent reduction in binding and reduced the binding of both full-length and truncated Aae proteins expressed in E. coli, as well as Aae expressed in Aa. Fluorescently labelled P40 peptides reacted in a dose-dependent manner with BEC receptors. We propose that these proof-of-principle experiments demonstrate that peptides can be designed to interfere with Aa binding mediated by host-cell receptors specific for Aae adhesins

Aggregatibacter actinomycetemcomitans (Aa) Under the Radar: Myths and Misunderstandings of Aa and Its Role in Aggressive Periodontitis

Aggregatibacter actinomycetemcomitans (Aa) is a low-abundance Gram-negative oral pathobiont that is highly associated with a silent but aggressive orphan disease that results in periodontitis and tooth loss in adolescents of African heritage. For the most part Aa conducts its business by utilizing strategies allowing it to conceal itself below the radar of the host mucosal immune defense system. A great deal of misinformation has been conveyed with respect to Aa biology in health and disease. The purpose of this review is to present misconceptions about Aa and the strategies that it uses to colonize, survive, and evade the host. In the process Aa manages to undermine host mucosal defenses and contribute to disease initiation. This review will present clinical observational, molecular, and interventional studies that illustrate genetic, phenotypic, and biogeographical tactics that have been recently clarified and demonstrate how Aa survives and suppresses host mucosal defenses to take part in disease pathogenesis. At one point in time Aa was considered to be the causative agent of Localized Aggressive Periodontitis. Currently, it is most accurate to look at Aa as a community activist and necessary partner of a pathogenic consortium that suppresses the initial host response so as to encourage overgrowth of its partners. The data for Aa's activist role stems from molecular genetic studies complemented by experimental animal investigations that demonstrate how Aa establishes a habitat (housing), nutritional sustenance in that habitat (food), and biogeographical mobilization and/or relocation from its initial habitat (transportation). In this manner Aa can transfer to a protected but vulnerable domain (pocket or sulcus) where its community activism is most useful. Aa's “strategy” includes obtaining housing, food, and transportation at no cost to its partners challenging the economic theory that “there ain't no such thing as a free lunch.” This “strategy” illustrates how co-evolution can promote Aa's survival, on one hand, and overgrowth of community members, on the other, which can result in local host dysbiosis and susceptibility to infection

Bacterial Infection Increases Periodontal Bone Loss in Diabetic Rats Through Enhanced Apoptosis

Periodontal disease is the most common osteolytic disease in humans and is significantly increased by diabetes mellitus. We tested the hypothesis that bacterial infection induces bone loss in diabetic animals through a mechanism that involves enhanced apoptosis. Type II diabetic rats were inoculated with Aggregatibacter actinomycetemcomitans and treated with a caspase-3 inhibitor, ZDEVD-FMK, or vehicle alone. Apoptotic cells were measured with TUNEL; osteoblasts and bone area were measured in H&E sections. New bone formation was assessed by labeling with fluorescent dyes and by osteocalcin mRNA levels. Osteoclast number, eroded bone surface, and new bone formation were measured by tartrate-resistant acid phosphatase staining. Immunohistochemistry was performed with an antibody against tumor necrosis factor-α. Bacterial infection doubled the number of tumor necrosis factor-α–expressing cells and increased apoptotic cells adjacent to bone 10-fold (P \u3c 0.05). Treatment with caspase inhibitor blocked apoptosis, increased the number of osteoclasts, and eroded bone surface (P \u3c 0.05); yet, inhibition of apoptosis resulted in significantly greater net bone area because of an increase in new bone formation, osteoblast numbers, and an increase in bone coupling. Thus, bacterial infection in diabetic rats stimulates periodontitis, in part through enhanced apoptosis of osteoblastic cells that reduces osseous coupling through a caspase-3–dependent mechanism. Diabetes is a chronic inflammatory disease characterized by hyperglycemia that affects 26 million Americans.1 Diabetes has several complications, such as cardiovascular, renal, microvascular, and periodontal diseases. Periodontal disease is one of the most common forms of osteolytic bone disease and one of the most frequent complications of the diabetes.2 Recent research suggests that the relationship between periodontitis and diabetes is reciprocal.3, 4 People with diabetes are more susceptible to periodontitis, and periodontitis may affect serum glucose levels and contribute to progression of diabetes.5 Diabetes may contribute to periodontitis because of its effect on inflammation.6, 7 Despite being triggered by bacterial infection, periodontal bone loss is tied to the inflammatory host response, which leads to the generation of prostaglandins and cytokines that stimulate osteoclastogenesis and periodontal bone loss.8 Several of the detrimental aspects of periodontal disease have recently been shown to be mediated by elevated levels of tumor necrosis factor-α (TNF-α).9, 10 TNF-α is a proinflammatory cytokine produced by leukocytes and other cell types.11 Enhanced TNF-α levels have been directly linked to cellular changes in diabetic retinopathy, deficits in wound healing, and diabetes-enhanced periodontitis.12, 13, 14 Some of the detrimental effects of diabetes-enhanced TNF-α levels may be because of the induction of cell death by triggering caspase activity. Caspases are a family of cysteine proteases that can act as either initiators (caspases 2, 8, and 9) or executioners (caspases 3, 6, and 7) of apoptosis.15 Caspase-3 appears to play a central role in bacteria and lipopolysaccharide-mediated apoptosis.16, 17 In addition, it has been shown that TNF-α can stimulate the expression of several pro-apoptotic genes, many of which are regulated by the pro-apoptotic transcription factor, forkhead box-O1 (FOXO1).18 The functional role of apoptosis in pathological processes can be studied with caspase inhibitors, which are small peptides that block the activity of well-defined caspases.19 These inhibitors have been used in animal models to attenuate cell death and diminish tissue damage in ischemic conditions, sepsis, and other pathological processes.20, 21 Other studies using caspase inhibitors have shown that part of the detrimental effect of diabetes on healing after infection is the result of increased fibroblast or osteoblast apoptosis.16, 22 To understand how diabetes may affect periodontal bone loss through apoptosis, we used a caspase-3/7 inhibitor in a type 2 Goto-Kakizaki (GK) diabetic rat model of periodontal disease induced by bacterial infection. The aim of this study was to determine how apoptosis of osteoblasts contributed to periodontal bone loss by its effect on bone formation in diabetic animals

A.Actinomycetemcomitans‐Induced Periodontal Disease Promotes Systemic and Local Responses in Rat Periodontium

Aim To characterize the histologic and cellular response to A. actinomycetemcomitans (Aa) infection. Material & Methods Wistar rats infected with Aa were evaluated for antibody response, oral Aa colonization, loss of attachment, PMN recruitment, TNF‐α in the junctional epithelium and connective tissue, osteoclasts and adaptive immune response in local lymph nodes at baseline and 4, 5 or 6 weeks after infection. Some groups were given antibacterial treatment at 4 weeks. Results An antibody response against Aa occurred within 4 weeks of infection, and 78% of inoculated rats had detectable Aa in the oral cavity (p \u3c 0.05). Aa infection significantly increased loss of attachment that was reversed by antibacterial treatment (p \u3c 0.05). TNF‐α expression in the junctional epithelium followed the same pattern. Aa stimulated high osteoclast formation and TNF‐α expression in the connective tissue (p \u3c 0.05). PMN recruitment significantly increased after Aa infection (p \u3c 0.05). Aa also increased the number of CD8+ T cells (p \u3c 0.05), but not CD4+ T cells or regulatory T cells (Tregs) (p \u3e 0.05). Conclusion Aa infection stimulated a local response that increased numbers of PMNs and TNF‐α expression in the junctional epithelium and loss of attachment. Both TNF‐α expression in JE and loss of attachment was reversed by antibiotic treatment. Aa infection also increased TNF‐α in the connective tissue, osteoclast numbers and CD8+ T cells in lymph nodes. The results link Aa infection with important characteristics of periodontal destruction

Lipopolysaccharide (LPS) potentiates hydrogen peroxide toxicity in T98G astrocytoma cells by suppression of anti-oxidative and growth factor gene expression

<p>Abstract</p> <p>Background</p> <p>Lipopolysaccharide (LPS) is a cell wall component of Gram-negative bacteria with proved role in pathogenesis of sepsis. Brain injury was observed with both patients dead from sepsis and animal septic models. However, <it>in vitro </it>administration of LPS has not shown obvious cell damage to astrocytes and other relative cell lines while it does cause endothelial cell death <it>in vitro</it>. These observations make it difficult to understand the role of LPS in brain parenchymal injury.</p> <p>Results</p> <p>To test the hypothesis that LPS may cause biological changes in astrocytes and make the cells to become vulnerable to reactive oxygen species, a recently developed highly sensitive and highly specific system for large-scale gene expression profiling was used to examine the gene expression profile of a group of 1,135 selected genes in a cell line, T98G, a derivative of human glioblastoma of astrocytic origin. By pre-treating T98G cells with different dose of LPS, it was found that LPS treatment caused a broad alteration in gene expression profile, but did not cause obvious cell death. However, after short exposure to H₂O₂, cell death was dramatically increased in the LPS pretreated samples. Interestingly, cell death was highly correlated with down-regulated expression of antioxidant genes such as cytochrome b561, glutathione s-transferase a4 and protein kinase C-epsilon. On the other hand, expression of genes encoding growth factors was significantly suppressed. These changes indicate that LPS treatment may suppress the anti-oxidative machinery, decrease the viability of the T98G cells and make the cells more sensitive to H₂O₂stress.</p> <p>Conclusion</p> <p>These results provide very meaningful clue for further exploring and understanding the mechanism underlying astrocyte injury in sepsis <it>in vivo</it>, and insight for why LPS could cause astrocyte injury <it>in vivo</it>, but not <it>in vitro</it>. It will also shed light on the therapeutic strategy of sepsis.</p