Supply chain reconfiguration for new product development through risk management approach

Nowadays, innovation is increasingly growing and the lifetime of products is decreasing. In this situation, New Product Development (NPD) is an advantage that makes it possible to survive in the competitive market. However, risks are unavoidable in NPD in any industry. Therefore, identifying, management, and mitigation of risks are considered of high significance for companies. By taking risk management into account, this study introduces a new multi-objective mathematical model for Supply Chain (SC) configuration in the presence of a new product. The considered SC is multi-echelon, multi-resource, multi-period, and multi-product. In order to manage the risk in this SC, appropriate mitigation strategies were chosen among various risk response strategies considering their cost and effectiveness. Furthermore, inuence of each choice on SC was accounted for in the mathematical model. The assumed model explored the optimum tactical and operational Supply Chain Management (SCM) decisions. The ability of the model was assessed by solving a numerical example. The result showed that the choice of various response strategies as well as new product production inuenced SC configuration

Withanolides-Induced Breast Cancer Cell Death Is Correlated with Their Ability to Inhibit Heat Protein 90

Withanolides are a large group of steroidal lactones found in Solanaceae plants that exhibit potential anticancer activities. We have previously demonstrated that a withanolide, tubocapsenolide A, induced cycle arrest and apoptosis in human breast cancer cells, which was associated with the inhibition of heat shock protein 90 (Hsp90). To investigate whether other withanolides are also capable of inhibiting Hsp90 and to analyze the structure-activity relationships, nine withanolides with different structural properties were tested in human breast cancer cells MDA-MB-231 and MCF-7 in the present study. Our data show that the 2,3-unsaturated double bond-containing withanolides inhibited Hsp90 function, as evidenced by selective depletion of Hsp90 client proteins and induction of Hsp70. The inhibitory effect of the withanolides on Hsp90 chaperone activity was further confirmed using in vivo heat shock luciferase activity recovery assays. Importantly, Hsp90 inhibition by the withanolides was correlated with their ability to induce cancer cell death. In addition, the withanolides reduced constitutive NF-κB activation by depleting IκB kinase complex (IKK) through inhibition of Hsp90. In estrogen receptor (ER)-positive MCF-7 cells, the withanolides also reduced the expression of ER, and this may be partly due to Hsp90 inhibition. Taken together, our results suggest that Hsp90 inhibition is a general feature of cytotoxic withanolides and plays an important role in their anticancer activity

Bone Marrow Transplantation Results in Human Donor Blood Cells Acquiring and Displaying Mouse Recipient Class I MHC and CD45 Antigens on Their Surface

Background: Mouse models of human disease are invaluable for determining the differentiation ability and functional capacity of stem cells. The best example is bone marrow transplants for studies of hematopoietic stem cells. For organ studies, the interpretation of the data can be difficult as transdifferentiation, cell fusion or surface antigen transfer (trogocytosis) can be misinterpreted as differentiation. These events have not been investigated in hematopoietic stem cell transplant models. Methodology/Principal Findings: In this study we investigated fusion and trogocytosis involving blood cells during bone marrow transplantation using a xenograft model. We report that using a standard SCID repopulating assay almost 100 % of the human donor cells appear as hybrid blood cells containing both mouse and human surface antigens. Conclusion/Significance: Hybrid cells are not the result of cell-cell fusion events but appear to be due to efficient surface antigen transfer, a process referred to as trogocytosis. Antigen transfer appears to be non-random and includes all donor cells regardless of sub-type. We also demonstrate that irradiation preconditioning enhances the frequency of hybrid cell

Anterior cruciate ligament reconstruction is associated with greater tibial tunnel widening when using a bioabsorbable screw compared to an all-inside technique with suspensory fixation

Purpose: To compare clinical outcomes and tunnel widening following anterior cruciate ligament reconstruction (ACLR) performed with an all-inside technique (Group A) or with a bioabsorbable tibial screw and suspensory femoral fixation (Group B). Methods: Tunnel widening was assessed using computed tomography (CT) and a previously validated analytical best fit cylinder technique at approximately 1-year following ACLR. Clinical follow-up comprised evaluation with IKDC, KSS, Tegner, Lysholm scores, and knee laxity assessment. Results: The study population comprised 22 patients in each group with a median clinical follow-up of 24 months (range 21–27 months). The median duration between ACLR and CT was 13 months (range 12–14 months). There were no significant differences in clinical outcome measures between groups. There were no differences between groups with respect to femoral tunnel widening. However, there was a significantly larger increase in tibial tunnel widening, at the middle portion, in Group B (2.4 ± 1.5 mm) compared to Group A (0.8 ± 0.4 mm) (p = 0.027), and also at the articular portion in Group B (1.5 ± 0.8 mm) compared to Group A (0.8 ± 0.8 mm) (p = 0.027). Conclusion: Tibial tunnel widening after ACLR using hamstring tendon autograft is significantly greater with suspensory femoral fixation and a bioabsorbable tibial interference screw when compared to an all-inside technique at a median follow-up of 2 years. The clinical relevance of this work lies in the rebuttal of concerns arising from biomechanical studies regarding the possibility of increased tunnel widening with an all-inside technique. Level of evidence: III