Mapping and simplifying construction project delivery

The nature of project complexity within construction engineering projects has been the subject of study with growing interest, especially since the Engineering and Physical Sciences Research Council (EPSRC) Networks- Engineering and Physical Sciences Research Council was set-up in 2003. Yet, it could be argued in research terms, that project complexity has been neglected both in terms of conceptualising it and in terms of empirical study. Given the supposed severity of project complexity and the obvious failings of the industry’s approach towards project delivery, it is reasonable to assume that such an issue would provide a focus for research to improve practice. The main issues appraised are structural complexity, uncertainty, organisational complexity and technological complexity. As established from the reviewed literature, one of the hindrances to project performance within the construction industry is project complexity, which mainly emerges during the construction and design process

TRPA1-mediated Ca²⁺

<p><b>influx in pancreatic beta cells. </b><b>a, b.</b> Application of AITC and MG induce an increase in intracellular Ca²⁺ in RIN cells (size of the bar is 100 µM). <b>c.</b> MG-induced Ca²⁺ influx is inhibited by TRPA1 antagonist HC030031. <b>d.</b> Ca²⁺ influx induced by endogenous ligands PGJ₂, 4-HNE, and AITC in RIN cells. <b>e.</b> Ca²⁺ influx induced by H₂O₂ and AITC in RIN cells. <b>f.</b> AITC-and MG-induced an increase in intracellular Ca²⁺ in rat cultured primary pancreatic beta cells.</p

TRPA1-mediated insulin release is independent of voltage-gated Na⁺, Ca²⁺ and K_ATP channels.

<p><b>a.</b> AITC caused a significant increase in insulin release (n=6, ** p<0.01). The basal insulin release is inhibited by incubation of RIN cells with TTX (1 µM) (TTX, n=6, * p<0.05. When challenged with AITC (200 µM), there is a significant increase in insulin release AITC+TTX, n=6, * p<0.05 as compared to TTX. <b>b.</b> In the presence of Ca²⁺ channel blocker nimodipine (5 µM) basal insulin release is decreased significantly (n=6, * p<0.05), but there is a significant increase when challenged with AITC+nimodipine (n=6,** p<0.01). <b>c.</b> In the presence of K_ATP channel opener, diazoxide (200 µM), basal insulin release is significantly decreased (n=6, * p<0.05), when challenged with AITC, there is a significant increase in insulin release (n=3, ** p<0.01).</p

Insulin release induced by different concentrations of glucose.

<p>a. Insulin release induced by different concentrations of glucose (6 mM, n=8, * p<0.001; 25 mM, n=9, *p<0.001) <b>b.</b> Insulin release induced by different concentrations of glucose is inhibited by HC030031 (100 µM) (6 mM, n=4, * p<0.001; 25 mM, n=7, * p<0.001, as compared to control). <b>c.</b> Insulin release induced by AITC (200 µM) in different concentrations of glucose is inhibited by HC030031 (100 µM) (6 mM, AITC, n=4, * p<0.01, AITC+HC030031, n=4, ** p<0.001; 25 mM, AITC, n=4, * p=0.023, AITC+HC030031, n=4, ** p<0.01).</p

TRPA1-mediated insulin release in pancreatic beta cell line and primary isolated pancreatic islets.

<p><b>a,b.</b> Dose-dependent increase in insulin release induced by AITC (0.1–1000 µM, <b>n=7</b>) and MG (0.1–1000 µM, <b>n=5</b>) in RIN cells (* p<0.05). <b>c,d.</b> AITC and MG induce a significant increase (AITC, n=11,* p<0.001; MG, n=10 * p=0.004) in insulin release from primary isolated pancreatic beta cell islets that could be blocked by the specific TRPA1 antagonist AP-18 (AITC+AP-18, n=6, ** p<0.001; MG+AP-18, n=6, ** p=0.008). <b>e.</b> 4-HNE (100 µM)-induced insulin release is inhibited by HC030031 (100 µM) (4-HNE, n=6, * p<0.001; 4-HNE+HC030031, n=3, ** p<0.001). <b>f.</b> PGJ₂ (20 µM)-induced insulin release is inhibited by HC030031 (100 µM) (PGJ₂, n=6, * p<0.001; PGJ₂+HC030031, n=3, ** p<0.001).</p

TRPA1-mediated membrane currents in primary pancreatic beta cells.

<p><b>a.</b> Membrane currents induced by extracellular application of MG and AITC in primary pancreatic beta cells. <b>b.</b> A concentration-response curve of membrane currents induced by MG included in the pipette solution in primary beta cells (EC₅₀=0.59 µM). Lower concentrations (∼1 µM) of MG are sufficient to induce maximal currents when applied intracellulary (inset), but the time to peak with lower concentrations is longer and the desensitization is profound at higher concentrations. <b>c.</b> Currents evoked by intracellular application of MG are reversibly blocked by extracellular application of AP-18. <b>d.</b> Currents elicited by MG and AITC in HEK 293T cells heterologously expressing TRPA1. <b>e.</b> MG-induced currents can be blocked by AP-18. <b>f.</b> Under current clamp conditions, extracellular application of MG depolarizes the membrane and generates action potentials that could be blocked by HC030031. <b>g.</b> Intracellular application of MG causes a robust depolarization and generates action potentials that could be blocked by HC030031.</p

Expression of TRPA1 in pancreatic beta cells.

<p><b>a.</b> RT-PCR shows the expression of TRPA1 mRNA in DRG neurons, whole pancreas (Pan), isolated islets (Isl), a pancreatic beta cell line (RIN), but not in a pancreatic alpha cell line (INR). <b>b.</b> Western blots show the expression of TRPA1 protein in RIN cells and HEK cells heterologously expressing TRPA1. c. Immunostaining of insulin (red), TRPA1 (green), and the co-expression (yellow) in the pancreatic islet (top panel). When the slices were incubated with the TRPA1 antibody after preabsorbing with a peptide used for making the antibody, the TRPA1 staining was considerably reduced (lower panel). The nuclei were stained with DAPI (scale bar=100 µM).</p