The impact of innovativeness on supply chain performance: is supply chain integration a missing link?

© Emerald Group Publishing Limited. Purpose - This purpose of this paper is to study the impact of innovativeness on supply chain integration (SCI) and supply chain performance (SCP) and the role of SCI in mediating between innovativeness in the supply chain and SCP. Innovativeness is an accepted driver to leverage firm performance. SCI and SCP require innovativeness in the supply chain, but their interrelationships have rarely been researched empirically.P Design/methodology/approach - A questionnaire survey and structural equation modelling were used in this work. After a structural and measurement model was devised from existing supply chain literature, the main data were collected in a web-based questionnaire survey of South Korean manufacturers. Structural equation modelling was applied to test proposed hypotheses on the associations between variables, following a hierarchical analysis process.P Findings - Innovativeness in the supply chain had a positive impact on both SCI and SCP. However, the direct impact of innovativeness on SCP disappeared when the model included SCI as a mediator. In specific, internal and supplier integration fully mediated innovativeness-SCP relationships, whereas customer integration had no mediating role on those relationships. The findings suggest that innovativeness can influence SCP only when the manufacturer’s level of SCI is sufficiently effective in developing necessary supply chain practices.P Research limitations/implications - In this work, innovativeness in the supply chain effectively influenced SCP through the mediation of SCI. However, cross-sectional analysis in one nation using one response per organisation invites validation embracing other geographical areas and longitudinal studies.P Practical implications - Design of an innovative culture within a firm and along a supply chain can enhance SCI practices by stimulating innovativeness. A high level of SCI should be pursued to effectively transform innovativeness into performance.P Originality/value - This work seminally examines the effect of innovativeness in the supply chain on SCI and SCP as well as the mediating role of SCI in the relationships between innovativeness and SCP

Cdk5 Phosphorylates Dopamine D2 Receptor and Attenuates Downstream Signaling

The dopamine D2 receptor (DRD2) is a key receptor that mediates dopamine-associated brain functions such as mood, reward, and emotion. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase whose function has been implicated in the brain reward circuit. In this study, we revealed that the serine 321 residue (S321) in the third intracellular loop of DRD2 (D2i3) is a novel regulatory site of Cdk5. Cdk5-dependent phosphorylation of S321 in the D2i3 was observed in in vitro and cell culture systems. We further observed that the phosphorylation of S321 impaired the agonist-stimulated surface expression of DRD2 and decreased G protein coupling to DRD2. Moreover, the downstream cAMP pathway was affected in the heterologous system and in primary neuronal cultures from p35 knockout embryos likely due to the reduced inhibitory activity of DRD2. These results indicate that Cdk5-mediated phosphorylation of S321 inhibits DRD2 function, providing a novel regulatory mechanism for dopamine signaling.X111111sciescopu

Differential regulation of BACE1 expression by oxidative and nitrosative signals

<p>Abstract</p> <p>Background</p> <p>It is well established that both cerebral hypoperfusion/stroke and type 2 diabetes are risk factors for Alzheimer's disease (AD). Recently, the molecular link between ischemia/hypoxia and amyloid precursor protein (APP) processing has begun to be established. However, the role of the key common denominator, namely nitric oxide (NO), in AD is largely unknown. In this study, we investigated redox regulation of BACE1, the rate-limiting enzyme responsible for the β-cleavage of APP to Aβ peptides.</p> <p>Results</p> <p>Herein, we studied events such as S-nitrosylation, a covalent modification of cysteine residues by NO, and H₂O₂-mediated oxidation. We found that NO and H₂O₂differentially modulate BACE1 expression and enzymatic activity: NO at low concentrations (<100 nM) suppresses BACE1 transcription as well as its enzymatic activity while at higher levels (0.1-100 μM) NO induces S-nitrosylation of BACE1 which inactivates the enzyme without altering its expression. Moreover, the suppressive effect on BACE1 transcription is mediated by the NO/cGMP-PKG signaling, likely through activated PGC-1α. H₂O₂(1-10 μM) induces BACE1 expression via transcriptional activation, resulting in increased enzymatic activity. The differential effects of NO and H₂O₂on BACE1 expression and activity are also reflected in their opposing effects on Aβ generation in cultured neurons in a dose-dependent manner. Furthermore, we found that BACE1 is highly S-nitrosylated in normal aging brains while S-nitrosylation is markedly reduced in AD brains.</p> <p>Conclusion</p> <p>This study demonstrates for the first time that BACE1 is highly modified by NO via multiple mechanisms: low and high levels of NO suppress BACE1 via transcriptional and post translational regulation, in contrast with the upregulation of BACE1 by H₂O₂-mediated oxidation. These novel NO-mediated regulatory mechanisms likely protect BACE1 from being further oxidized by excessive oxidative stress, as from H₂O₂and peroxynitrite which are known to upregulate BACE1 and activate the enzyme, resulting in excessive cleavage of APP and Aβ generation; they likely represent the crucial house-keeping mechanism for BACE1 expression/activation under physiological conditions.</p

Monte Carlo Simulation of Sinusoidally Modulated Superlattice Growth

The fabrication of ZnSe/ZnTe superlattices grown by the process of rotating the substrate in the presence of an inhomogeneous flux distribution instead of successively closing and opening of source shutters is studied via Monte Carlo simulations. It is found that the concentration of each compound is sinusoidally modulated along the growth direction, caused by the uneven arrival of Se and Te atoms at a given point of the sample, and by the variation of the Te/Se ratio at that point due to the rotation of the substrate. In this way we obtain a ZnSe$_{1-x}$Te$_x$ alloy in which the composition $x$ varies sinusoidally along the growth direction. The period of the modulation is directly controlled by the rate of the substrate rotation. The amplitude of the compositional modulation is monotonous for small angular velocities of the substrate rotation, but is itself modulated for large angular velocities. The average amplitude of the modulation pattern decreases as the angular velocity of substrate rotation increases and the measurement position approaches the center of rotation. The simulation results are in good agreement with previously published experimental measurements on superlattices fabricated in this manner