A framework for the integration of green and lean six sigma for superior sustainability performance

Evidence suggests that Lean, Six Sigma and Green approaches make a positive contribution to the economic, social and environmental (i.e. sustainability) performance of organizations. However, evidence also suggests that organizations have found their integration and implementation challenging. The purpose of this research is therefore to present a framework that methodically guides companies through a five stages and sixteen steps process to effectively integrate and implement the Green, Lean and Six Sigma approaches to improve their sustainability performance. To achieve this, a critical review of the existing literature in the subject area was conducted to build a research gap, and subsequently develop the methodological framework proposed. The paper presents the results from the application of the proposed framework in four organizations with different sizes and operating in a diverse range of industries. The results showed that the integration of Lean Six Sigma and Green helped the organizations to averagely reduce their resources consumption from 20% to 40% and minimize the cost of energy and mass streams by 7-12%. The application of the framework should be gradual, the companies should assess their weaknesses and strengths, set priorities, and identify goals for successful implementation. This paper is one of the very first researches that presents a framework to integrate Green and Lean Six Sigma at a factory level, and hence offers the potential to be expanded to multiple factories or even supply chains

Enzymatic and analytical tools for the characterization of chondroitin sulfate and dermatan sulfate glycosaminoglycans

Thesis (Ph. D. in Applied Biosciences and Biotechnology)--Massachusetts Institute of Technology, Biological Engineering Division, 2003.Includes bibliographical references (p. 113-123).Glycosaminoglycans (GAGs) are complex polysaccharides that reside in the extracellular matrix and on the surfaces of all cells. The same complexity that contributes to the diversity of GAG function has also hindered their chemical characterization. Recent progress in coupling bacterial GAG-degrading enzymes with sensitive analytical techniques has led to a revolution in understanding the structure-function relationship for an important subset of GAGs, namely heparin/heparan sulfate-like glycosaminoglycans (HSGAGs). The study of chondroitin sulfate and dermatan sulfate (CS/DS), an equally important subset of GAGs, has lagged behind partially due to a lack of enzymatic and analytical tools akin to those developed for HSGAGs. The Flavobacterial heparinases have proven indispensable in characterizing the fine structure of HSGAGs responsible for their different biological functions. As a continuation of ongoing research, a combination of chemical modification, peptide mapping, and site-directed mutagenesis was employed to explore the role of histidine in the activity of heparinase III. Of the thirteen histidines in the enzyme, His295 and His510 were found to be critical for the degradation of heparan sulfate by heparinase III. As a first step to developing the chondroitinases as enzymatic tools for the characterization of CS/DS oligosaccharides, recombinant expression and purification schemes were developed for chondroitinase AC and B from Flactobacterium heparinum. The recombinant enzymes were characterized using biochemical techniques and kinetic parameters were determined for their respective CS/DS substrates.(cont.) By combining the modeling a tetrasaccharide substrate into the active site of chondroitinase B with site-directed mutagenesis studies, a variety of residues were identified as critical for substrate binding and catalysis. A subsequent co-crystal structure of chondroitinase B with DS-derived hexasaccharide revealed a catalytic role for a calcium ion and provided further clarity into the role of individual active site amino acids. Additionally, using a variety of defined DS-derived oligosaccharides coupled with sensitive analytical techniques, chondroitinase B was identified as an endolytic, non-random, non-processive enzyme that preferentially cleaves longer oligosaccharides compared to shorter ones. Taken together, these studies represent a critical step in developing the chondroitinases as enzymatic tools for the characterization of CS/DS oligosaccharides in a fashion akin to the use of the heparinases to characterize HSGAGs.by Kevin R. Pojasek.Ph.D.in Applied Biosciences and Biotechnolog

The tetrahydrobiopterin pathway and pain

Novel approaches for treating chronic pain are required to address a widely recognized, yet largely underserved and unmet, clinical need. The recently discovered link between tetrahydrobiopterin (BH4) synthesis and pain in preclinical models and humans provides a promising new approach for treating neuropathic and other forms of chronic pain. The rate-limiting enzyme in BH4 synthesis, guanosine triphosphate cyclohydrolase 1 (GCH1), and sepiapterin reductase (SPR) are both promising drug targets based on initial active-site characterization of the SARs of these two enzymes. Reducing the elevated BH4 levels associated with pain to baseline, while maintaining sufficient BH4 levels to limit side effects is the goal of discovery programs for novel therapeutics targeting GCH1 or SPR.</p

Identification of essential residues within Lit, a cell death peptidase of Escherichia coli K-12.

Bacteriophage exclusion is a suicide response to viral infection. In strains of Escherichia coli K-12 infected with T4 phage this process is mediated by the host-encoded Lit peptidase. Lit is activated by a unique sequence in the major head protein of the T4 phage (the Gol sequence) which then cleaves site-specifically the host translation factor EF-Tu, ultimately leading to cell death. Lit has very low sequence identity with other peptidases, with only a putative metallopeptidase motif, H(160)EXXH, giving an indication of its catalytic activity. The aim of the present study was to ascertain if Lit is a metallopeptidase, identify residues essential for Lit activity, and probe the involvement of the Gol sequence in the activation of enzymatic activity. Lit activity was inhibited by the zinc chelator 1,10-phenanthroline, consistent with the suggestion that it is a metallopeptidase. Preliminary covalent modification experiments found that Lit was susceptible to inactivation by diethyl pyrocarbonate, with about three histidines reversibly modified, one of which was found to be essential for proteolytic activity. Subsequently, 13 mutants of the Lit enzyme were constructed that included all 10 histidines as well as other residues within the metallopeptidase motif. This demonstrated that the residues within the HEXXH motif are required for Lit activity and further defined the essential catalytic core as H(160)EXXHX(67)H, with additional residues such as His169 being important but not essential for activity. Kinetic analysis of Lit activation by a synthetic Gol peptide highlighted that elevated concentrations of the peptide (>10-fold above activation K(M)) are inhibitory to Lit, with this effect also seen in partially active Lit mutants. The susceptibility of Lit to inhibition by its own activating peptide suggests that the Gol sequence may be able to bind nonproductively to the enzyme at high concentration. We discuss these data in the context of the currently understood models for Gol-mediated activation of the Lit peptidase and its mechanism of action