A Synergistic Approach to Process Innovation

With the continuing globalisation of the economy comes increasing number of competitors. Consequently, products lifecycles has continued to fall as companies strive to out-manoeuvre one another by introducing product and service innovations to meet the needs of increasingly choosy customers. This has created a business environment where change has become widespread and persistent. As processes are the engines that power organisations to deliver the values required by customers, it becomes imperative that to have competitive edge, or even survive in this sort of business environment, these processes need to be not only adaptable to the changes but also be capable of inducing the changes that would benefit the organisations. To investigate the feasibility of adaptable and change inducing processes, the research presented in this paper explores the synergies amongst three techniques for problems solving and process improvement: Theory of Inventive Problem Solving, which is more commonly known by its Russian acronym, TRIZ; Theory of Constraints (TOC); and Lean Manufacturing.N/

MESSI: metabolic engineering target selection and best strain identification tool

Metabolic engineering and synthetic biology are synergistically related fields for manipulating target pathways and designing microorganisms that can act as chemical factories. Saccharomyces cerevisiae’s ideal bioprocessing traits make yeast a very attractive chemical factory for production of fuels, pharmaceuticals, nutraceuticals as well as a wide range of chemicals. However, future attempts of engineering S. cerevisiae’s metabolism using synthetic biology need to move towards more integrative models that incorporate the high connectivity of metabolic pathways and regulatory processes and the interactions in genetic elements across those pathways and processes. To contribute in this direction, we have developed Metabolic Engineering target Selection and best Strain Identification tool (MESSI), a web server for predicting efficient chassis and regulatory components for yeast bio-based production. The server provides an integrative platform for users to analyse ready-to-use public high-throughput metabolomic data, which are transformed to metabolic pathway activities for identifying the most efficient S. cerevisiae strain for the production of a compound of interest. As input MESSI accepts metabolite KEGG IDs or pathway names. MESSI outputs a ranked list of S. cerevisiae strains based on aggregation algorithms. Furthermore, through a genome-wide association study of the metabolic pathway activities with the strains’ natural variation, MESSI prioritizes genes and small variants as potential regulatory points and promising metabolic engineering targets. Users can choose various parameters in the whole process such as (i) weight and expectation of each metabolic pathway activity in the final ranking of the strains, (ii) Weighted AddScore Fuse or Weighted Borda Fuse aggregation algorithm, (iii) type of variants to be included, (iv) variant sets in different biological levels. Database URL: http://sbb.hku.hk/MESSI

Involvement of Physical Parameters in Medium Improvement for Tannase Production by Aspergillus niger FETL FT3 in Submerged Fermentation

Aspergillus niger FETL FT3, a local extracellular tannase producer strain that was isolated from one of dumping sites of tannin-rich barks of Rhizophora apiculata in Perak, Malaysia. This fungus was cultivated in 250 mL Erlenmeyer flask under submerged fermentation system. Various physical parameters were studied in order to maximize the tannase production. Maximal yield of tannase production, that is, 2.81 U per mL was obtained on the fourth day of cultivation when the submerged fermentation was carried out using liquid Czapek-Dox medium containing (percent; weight per volume) 0.25% NaNO3, 0.1% KH2PO4, 0.05% MgSO4 ·7H2O, 0.05% KCl, and 1.0% tannic acid. The physical parameters used initial medium pH of 6.0, incubation temperature of 30°C, agitation speed of 200 rpm and inoculums size of 6 × 106 spores/ ml. This research has showed that physical parameters were influenced the tannase production by the fungus with 156.4 percent increment

Theory of the propagation of coupled waves in arbitrarily-inhomogeneous stratified media

We generalize the invariant imbedding theory of the wave propagation and derive new invariant imbedding equations for the propagation of arbitrary number of coupled waves of any kind in arbitrarily-inhomogeneous stratified media, where the wave equations are effectively one-dimensional. By doing this, we transform the original boundary value problem of coupled second-order differential equations to an initial value problem of coupled first-order differential equations, which makes the numerical solution of the coupled wave equations much easier. Using the invariant imbedding equations, we are able to calculate the matrix reflection and transmission coefficients and the wave amplitudes inside the inhomogeneous media exactly and efficiently. We establish the validity and the usefulness of our results by applying them to the propagation of circularly-polarized electromagnetic waves in one-dimensional photonic crystals made of isotropic chiral media. We find that there are three kinds of bandgaps in these structures and clarify the nature of these bandgaps by exact calculations.Comment: 7 pages, 1 figure, to appear in Europhys. Let

Nuclear expression of Lyn, a Src family kinase member, is associated with poor prognosis in renal cancer patients

Background: 8000 cases of renal cancer are diagnosed each year in the UK, with a five-year survival rate of 50 %. Treatment options are limited; a potential therapeutic target is the Src family kinases (SFKs). SFKs have roles in multiple oncogenic processes and promote metastases in solid tumours. The aim of this study was to investigate SFKs as potential therapeutic targets for clear cell renal cell carcinoma (ccRCC). Methods: SFKs expression was assessed in a tissue microarray consisting of 192 ccRCC patients with full clinical follow-up. SFK inhibitors, dasatinib and saracatinib, were assessed in early ccRCC cell lines, 786-O and 769-P and a metastatic ccRCC cell line, ACHN (± Src) for effects on protein expression, apoptosis, proliferation and wound healing. Results: High nuclear expression of Lyn and the downstream marker of activation, paxillin, were associated with decreased patient survival. Conversely, high cytoplasmic expression of other SFK members and downstream marker of activation, focal adhesion kinase (FAK) were associated with increased patient survival. Treatment of non-metastatic 786-O and 769-P cells with dasatinib, dose dependently reduced SFK activation, shown via SFK (Y419) and FAK (Y861) phosphorylation, with no effect in metastatic ACHN cells. Dasatinib also increased apoptosis, while decreasing proliferation and migration in 786-O and 769-P cell lines, both in the presence and absence of Src protein. Conclusions: Our data suggests that nuclear Lyn is a potential therapeutic target for ccRCC and dasatinib affects cellular functions associated with cancer progression via a Src kinase independent mechanism

Rotating Electromagnetic Waves in Toroid-Shaped Regions

Electromagnetic waves, solving the full set of Maxwell equations in vacuum, are numerically computed. These waves occupy a fixed bounded region of the three dimensional space, topologically equivalent to a toroid. Thus, their fluid dynamics analogs are vortex rings. An analysis of the shape of the sections of the rings, depending on the angular speed of rotation and the major diameter, is carried out. Successively, spherical electromagnetic vortex rings of Hill's type are taken into consideration. For some interesting peculiar configurations, explicit numerical solutions are exhibited.Comment: 27 pages, 40 figure

Clinical translation of [18F]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer

Background: Effective anticancer therapy is thought to involve induction of tumour cell death through apoptosis and/or necrosis. [18F]ICMT-11, an isatin sulfonamide caspase-3/7-specific radiotracer, has been developed for PET imaging and shown to have favourable dosimetry, safety, and biodistribution. We report the translation of [18F]ICMT-11 PET to measure chemotherapy-induced caspase-3/7 activation in breast and lung cancer patients receiving first-line therapy. Results: Breast tumour SUVmax of [18F]ICMT-11 was low at baseline and unchanged following therapy. Measurement of M30/M60 cytokeratin-18 cleavage products showed that therapy was predominantly not apoptosis in nature. While increases in caspase-3 staining on breast histology were seen, post-treatment caspase-3 positivity values were only approximately 1%; this low level of caspase-3 could have limited sensitive detection by [18F]ICMT-11-PET. Fourteen out of 15 breast cancer patients responded to first–line chemotherapy (complete or partial response); one patient had stable disease. Four patients showed increases in regions of high tumour [18F]ICMT-11 intensity on voxel-wise analysis of tumour data (classed as PADS); response was not exclusive to patients with this phenotype. In patients with lung cancer, multi-parametric [18F]ICMT-11 PET and MRI (diffusion-weighted- and dynamic contrast enhanced-MRI) showed that PET changes were concordant with cell death in the absence of significant perfusion changes. Conclusion: This study highlights the potential use of [18F]ICMT-11 PET as a promising candidate for non-invasive imaging of caspase3/7 activation, and the difficulties encountered in assessing early-treatment responses. We summarize that tumour response could occur in the absence of predominant chemotherapy-induced caspase-3/7 activation measured non-invasively across entire tumour lesions in patients with breast and lung cancer

Quantum Gauge Equivalence in QED

We discuss gauge transformations in QED coupled to a charged spinor field, and examine whether we can gauge-transform the entire formulation of the theory from one gauge to another, so that not only the gauge and spinor fields, but also the forms of the operator-valued Hamiltonians are transformed. The discussion includes the covariant gauge, in which the gauge condition and Gauss's law are not primary constraints on operator-valued quantities; it also includes the Coulomb gauge, and the spatial axial gauge, in which the constraints are imposed on operator-valued fields by applying the Dirac-Bergmann procedure. We show how to transform the covariant, Coulomb and spatial axial gauges to what we call ``common form,'' in which all particle excitation modes have identical properties. We also show that, once that common form has been reached, QED in different gauges has a common time-evolution operator that defines time-translation for states that represent systems of electrons and photons. By combining gauge transformations with changes of representation from standard to common form, the entire apparatus of a gauge theory can be transformed from one gauge to another.Comment: Contribution for a special issue of Foundations of Physics honoring Fritz Rohrlich; edited by Larry P. Horwitz, Tel-Aviv University, and Alwyn van der Merwe, University of Denver (Plenum Publishing, New York); 40 pages, REVTEX, Preprint UCONN-93-3, 1 figure available upon request from author