Dietary supplementation of vitamin E and -lipoic acid upregulates cell growth and signaling genes in rat myocardium

The efficacy of antioxidant supplementation in the prevention of cardiovascular disease appears equivocal, however the use of more potent antioxidant combinations than those traditionally used may exert a more positive effect. We have shown previously that supplementation of vitamin E and α-lipoic acid increases cardiac performance during post-ischemia reperfusion in older rats and increases Bcl-2 levels in endothelial cells. The purpose of this study was to examine the effects of vitamin E and α-lipoic acid supplementation on myocardial gene expression with a view to determine their mechanism of action. Young male rats received either a control (n=7) or vitamin E and α-lipoic acid supplemented diet (n=8) for 14 weeks. RNA from myocardial tissue was then amplified and samples were pooled within groups and competitively hybridized to 5K oligonucleotide rat microarrays. The relative expression of each gene was then compared to the control sample. Animals that received the antioxidant-supplemented diet exhibited upregulation (>1.5×) of 13 genes in the myocardium with 2 genes downregulated.� �Upregulated genes include those involved in cell growth and maintenance (LynB, Csf1r, Akt2, Tp53), cell signaling (LynB, Csf1r) and signal transduction (Pacsin2, Csf1r). Downregulated genes encode thyroid (Thrsp) and F-actin binding proteins (Nexilin).

The PCNA-associated factor KIAA0101/p15(PAF) binds the potential tumor suppressor product p33ING1b

The KIAA0101/p15(PAF)/OEATC-1 protein was initially isolated in a yeast two-hybrid screen for proliferating cell nuclear antigen (PCNA) binding partners, and was shown to bind PCNA competitively with the cell cycle regulator p21(WAF). PCNA is involved in DNA replication and damage repair. Using polyclonal antisera raised against a p15(PAF) fusion protein, we have shown that in a range of mammalian tumor and non-tumor cell lines the endogenous p15(PAF) protein localises to the nucleus and the mitochondria. Under normal conditions no co-localisation with PCNA could be detected, however following exposure to UV it was possible to co-immunoprecipitate p15(PAF) and PCNA from a number of cell lines, suggesting a UV-enhanced association of the two proteins. Overexpression of p15(PAF) in mammalian cells was also found to protect cells from UV-induced cell death. Based on similarities between the behaviour of p15(PAF) and the potential tumor suppressor product p33ING1b, we have further shown that these two proteins interact in the same complex in cell cultures. This suggests that p15(PAF) forms part of a larger protein complex potentially involved in the regulation of DNA repair, apoptosis and cell cycle progression. (c) 2005 Elsevier Inc. All rights reserved.

Associative knowledge controls deployment of visual selective attention

According to some models of visual selective attention, objects in a scene activate corresponding neural representations, which compete for perceptual awareness and motor behavior. During a visual search for a target object, top-down control exerted by working memory representations of the target's defining properties resolves competition in favor of the target. These models, however, ignore the existence of associative links among object representations. Here we show that such associations can strongly influence deployment of attention in humans. In the context of visual search, objects associated with the target were both recalled more often and recognized more accurately than unrelated distractors. Notably, both target and associated objects competitively weakened recognition of unrelated distractors and slowed responses to a luminance probe. Moreover, in a speeded search protocol, associated objects rendered search both slower and less accurate. Finally, the first saccades after onset of the stimulus array were more often directed toward associated than control items.

Comparative performance of analytical techniques for polyhexamethylene biguanide (PHMB) in ophthalmic solutions

Purpose: The use of PHMB as a disinfectant in contact lens multipurpose solutions has been at the centre of much debate in recent times, particularly in relation to the issue of solution induced corneal staining. Clinical studies have been carried out which suggest different effects with individual contact lens materials used in combination with specific PHMB containing care regimes. There does not appear to be, however, a reliable analytical technique that would detect and quantify with any degree of accuracy the specific levels of PHMB that are taken up and released from individual solutions by the various contact lens materials. Methods: PHMB is a mixture of positively charged polymer units of varying molecular weight that has maximum absorbance wavelength of 236 nm. On the basis of these properties a range of assays including capillary electrophoresis, HPLC, a nickelnioxime colorimetric technique, mass spectrophotometry, UV spectroscopy and ion chromatography were assessed paying particular attention to each of their constraints and detection levels. Particular interest was focused on the relative advantage of contactless conductivity compared to UV and mass spectrometry detection in capillary electrophoresis (CE). This study provides an overview of the comparative performance of these techniques. Results: The UV absorbance of PHMB solutions, ranging from 0.0625 to 50 ppm was measured at 236 nm. Within this range the calibration curve appears to be linear however, absorption values below 1 ppm (0.0001%) were extremely difficult to reproduce. The concentration of PHMB in solutions is in the range of 0.0002–0.00005% and our investigations suggest that levels of PHMB below 0.0001% (levels encountered in uptake and release studies) can not be accurately estimated, in particular when analysing complex lens care solutions which can contain competitively absorbing, and thus interfering, species in the solution. The use of separative methodologies, such as CE using UV detection alone is similarly limited. Alternative techniques including contactless conductivity detection offer greater discrimination in complex solutions together with the opportunity for dual channel detection. Preliminary results achieved by TraceDec1 contactless conductivity detection, (Gain 150%, Offset 150) in conjunction with the Agilent capillary electrophoresis system using a bare fused silica capillary (extended light path, 50 mid, total length 64.5 cm, effective length 56 cm) and a cationic buffer at pH 3.2, exhibit great potential with reproducible PHMB split peaks. Conclusions: PHMB-based solutions are commonly associated with the potential to invoke corneal staining in combination with certain contact lens materials. However this terminology ‘PHMBbased solution’ is used primarily because PHMB itself has yet to be adequately implicated as the causative agent of the staining and compromised corneal cell integrity. The lack of well characterised adequately sensitive assays, coupled with the range of additional components that characterise individual care solutions pose a major barrier to the investigation of PHMB interactions in the lenswearing eye.

A configuration framework of manufacturing strategy paradigm in state owned enterprises within China's petrochemical industry:building context-embedded configurations for the paradigm of strategic manufacturing management from exploratory case studies

The role of the production system as a key determinant of competitive performance of business operations- has long been the subject of industrial organization research, even predating the .explicit conceptua1isation of manufacturing, strategy in the literature. Particular emergent production issues such as the globalisation of production, global supply chain management, management of integrated manufacturing and a growing e~busjness environment are expected to critically influence the overall competitive performance and therefore the strategic success of the organization. More than ever, there is a critical need to configure and improve production system and operations competence in a strategic way so as to contribute to the long-term competitiveness of the organization. In order to operate competitively and profitably, manufacturing companies, no matter how well managed, all need a long-term 'strategic direction' for the development of operations competence in order to consistently produce more market value with less cost towards a leadership position. As to the long-term competitiveness, it is more important to establish a dynamic 'strategic perspective' for continuous operational improvements in pursuit of this direction, as well as ongoing reviews of the direction in relation to the overall operating context. However, it also clear that the 'existing paradigm of manufacturing strategy development' is incapable of adequately responding to the increasing complexities and variations of contemporary business operations. This has been factually reflected as many manufacturing companies are finding that methodologies advocated in the existing paradigm for developing manufacturing strategy have very limited scale and scope for contextual contingency in empirical application. More importantly, there has also emerged a deficiency in the multidimensional and integrative profile from a theoretical perspective when operationalising the underlying concept of strategic manufacturing management established in the literature. The point of departure for this study was a recognition of such contextual and unitary limitations in the existing paradigm of manufacturing strategy development when applied to contemporary industrial organizations in general, and Chinese State Owned Enterprises (SOEs) in particular. As China gradually becomes integrated into the world economy, the relevance of Western management theory and its paradigm becomes a practical matter as much as a theoretical issue. Since China markedly differs from Western countries in terms of culture, society, and political and economic systems, it presents promising grounds to test and refine existing management theories and paradigms with greater contextual contingency and wider theoretical perspective. Under China's ongoing programmes of SOE reform, there has been an increased recognition that strategy development is the very essence of the management task for managers of manufacturing companies in the same way as it is for their counterparts in Western economies. However, the Western paradigm often displays a rather naive and unitary perspective of the nature of strategic management decision-making, one which largely overlooks context-embedded factors and social/political influences on the development of manufacturing strategy. This thesis studies the successful experiences of developing manufacturing strategy from five high-performing large-scale SOEs within China’s petrochemical industry. China’s petrochemical industry constitutes a basic heavy industrial sector, which has always been a strategic focus for reform and development by the Chinese government. Using a confirmation approach, the study has focused on exploring and conceptualising the empirical paradigm of manufacturing strategy development practiced by management. That is examining the ‘empirical specifics’ and surfacing the ‘managerial perceptions’ of content configuration, context of consideration, and process organization for developing a manufacturing strategy during the practice. The research investigation adopts a qualitative exploratory case study methodology with a semi-structural front-end research design. Data collection follows a longitudinal and multiple-case design and triangulates case evidence from sources including qualitative interviews, direct observation, and a search of documentations and archival records. Data analysis follows an investigative progression from a within-case preliminary interpretation of facts to a cross-case search for patterns through theoretical comparison and analytical generalization. The underlying conceptions in both the literature of manufacturing strategy and related studies in business strategy were used to develop theoretical framework and analytical templates applied during data collection and analysis. The thesis makes both empirical and theoretical contributions to our understanding of 'contemporary management paradigm of manufacturing strategy development'. First, it provides a valuable contextual contingency of the 'subject' using the business setting of China's SOEs in petrochemical industry. This has been unpacked into empirical configurations developed for its context of consideration, its content and process respectively. Of special note, a lean paradigm of business operations and production management discovered at case companies has significant implications as an emerging alternative for high-volume capital intensive state manufacturing in China. Second, it provides a multidimensional and integrative theoretical profile of the 'subject' based upon managerial perspectives conceptualised at case companies when operationalising manufacturing strategy. This has been unpacked into conceptual frameworks developed for its context of consideration, its content constructs, and its process patterns respectively. Notably, a synergies perspective towards the operating context, competitive priorities and competence development of business operations and production management has significant implications for implementing a lean manufacturing paradigm. As a whole, in so doing, the thesis established a theoretical platform for future refinement and development of context-specific methodologies for developing manufacturing strategy.

Soft [beta]-adrenoceptor agonists for topical use in psoriasis

Psoriasis is characterised by epidermal proliferation and inflammation resulting in the appearance of elevated erythematous plaques. The ratio of c~AMP/c~GMP is decreased in psoriatic skin and when the epidermal cell surface receptors are stimulated by β-adrenergic agonists, intracellular ATP is transformed into c-AMP, thus restoring the c~AMP/c~GMP levels. This thesis describes a series of β-adrenoceptor agonists for topical delivery based upon the soft-drug approach. Soft drugs are defined as biologically active, therapeutically useful chemical compounds (drugs) characterised by a predictable and controllable In vivo destruction (metabolism) to non-toxic moieties. after they achieve their therapeutic role, The N-substituent can accommodate a broad range of structures and here the alkoxycarbonylethyl group has been used to provide metabolic susceptability. The increased polarity of the dihydroxy acid, expected after metabolic conversion of the soft~drug, ethyl N-[2'-(3',4'-dihydroxyphenyl)-2'-hydroxyethyl]-3- aminopropionate, should eliminate agonist activity. Further. to prevent oxidation and enhance topical delivery, the catechol hydroxyl groups have been esterified to produce a pro-soft-drug which generates the soft-drug in enzymic systems. The chemical hydrolysis of the pro-soft-drug proceeded via the formation of the dlpivaloyloxy acid and it failed to generate the active dihydroxy ester soft-drug. In contrast, in the presence of porcine liver carboxyesterase, the hydrolysis of the pro-soft drug proceeded via the formation of the required active soft-drug. This compound, thus, has the appropnate kinetic features to enable it to be evaluated further as a drug for the treatment of psoriasis. The pH rate-profile for the hydrolysis of soft-drug indicated a maximum stability at pH ∼ 4.0. The individual rate constants for the degradation and the pKa were analysed by nonlinear regression. The pKa of 7.40 is in excellent agreement with that determined by direct titration (7.43) and indicates that satisfactory convergence was achieved. The soft-drug was poorly transported across a silicone membrane; it was also air-sensitive due to oxidation of the catechol group. The transport of the pro-soft-drug was more efficient and, over the donor pH range 3-8, increased with pH. At lower values, the largely protonated species was not transported. However, above pH 7. chemical degradation was rapid so that a donor pH of 5-6 was optimum. The β-adrenergic agonist activity of these compounds was tested in vitro by measuring chronotropic and inotropic responses in the guinea pig atria and relaxation of guinea pig trachea precontracted with acetylcholine (10-3 M). The soft~drug was a full agonist on the tracheal preparation but was less potent than isoprenaline. Responses of the soft~drug were competitively antagonised by propranolol (10-6 M). The soft~drug produced an increase in force and rate of the isolated atrial preparatIon. The propyl analogue was equally potent with ED50 of 6.52 x 10-7 M. In contrast, at equivalent doses, the dihydroxy acid showed no activity; only a marginal effect was observed on the tracheal preparation. For the pro~soft-drug, responses were of slow onset, in both preparations, with a slowly developing relaxatlon of the tracheal preparatlon at high concentrations (10-5 M). This is consistent with in vitro results where the dipivaloyl groups are hydrolysed more readily than the ethyl ester to gIve the active soft-drug. These results confirm the validity tif the pro-soft-drug approach to the deUvery of β-adrenoceptor agonists.

Organisational receptivity for change:combining context and capability to explain competitive advantage

This thesis explores efforts to conjoin organisational contexts and capabilities in explaining sustainable competitive advantage. Oliver (1997) argued organisations need to balance the need to conform to industry’s requirements to attain legitimization (e.g. DiMaggio & Powell, 1983), and the need for resource optimization (e.g. Barney, 1991). The author hypothesized that such balance can be viewed as movements along the homogeneity-heterogeneity continuum. An organisation in a homogenous industry possesses similar characteristics as its competitors, as opposed to a heterogeneous industry in which organisations within are differentiated and competitively positioned (Oliver, 1997). The movement is influenced by the dynamic environmental conditions that an organisation is experiencing. The author extended Oliver’s (1997) propositions of combining RBV’s focus on capabilities with institutional theory’s focus on organisational context, as well as redefining organisational receptivity towards change (ORC) factors from Butler and Allen’s (2008) findings. The authors contributed to the theoretical development of ORC theory to explain the attainment of sustainable competitive advantage. ORC adopts the assumptions from both institutional and RBV theories, where the receptivity factors include both organisational contexts and capabilities. The thesis employed a mixed method approach in which sequential qualitative quantitative studies were deployed to establish a robust, reliable, and valid ORC scale. The adoption of Hinkin’s (1995) three-phase scale development process was updated, thus items generated from interviews and literature reviews went through numerous exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to achieve convergent, discriminant, and nomological validities. Samples in the first phase (semi structured interviews) were hotel owners and managers. In the second phase, samples were MBA students, and employees of private and public sectors. In the third phase, samples were hotel managers. The final ORC scale is a parsimonious second higher-order latent construct. The first-order constructs comprises four latent receptivity factors which are ideological vision (4 items), leading change (4 items), implementation capacity (4 items), and change orientation (7 items). Hypotheses testing revealed that high levels of perceived environmental uncertainty leads to high levels of receptivity factor. Furthermore, the study found a strong positive correlation between receptivity factors and competitive advantage, and between receptivity factors and organisation performance. Mediation analyses revealed that receptivity factors partially mediate the relationship between perceived environmental uncertainty, competitive advantage and organisational performance.

Evolutionary market agents for resource allocation in decentralised systems

We introduce self-interested evolutionary market agents, which act on behalf of service providers in a large decentralised system, to adaptively price their resources over time. Our agents competitively co-evolve in the live market, driving it towards the Bertrand equilibrium, the non-cooperative Nash equilibrium, at which all sellers charge their reserve price and share the market equally. We demonstrate that this outcome results in even load-balancing between the service providers. Our contribution in this paper is twofold; the use of on-line competitive co-evolution of self-interested service providers to drive a decentralised market towards equilibrium, and a demonstration that load-balancing behaviour emerges under the assumptions we describe. Unlike previous studies on this topic, all our agents are entirely self-interested; no cooperation is assumed. This makes our problem a non-trivial and more realistic one.

Artificial reefs concentrate nutrients and alter benthic community structure in an oligotrophic, subtropical estuary

The construction of artificial reefs in the oligotrophic seagrass meadows of central Florida Bay attracted large aggregations of fish and invertebrates, and assays of nutrient availability indicated increases in availability of nutrients to sediment microalgae, periphyton, and seagrasses around reefs. An average of 37.8 large (> 10 cm) mobile animals were observed on each small artificial reef. The dominant fish species present was the gray snapper (Lutjanus griseus Linnaeus, 1758). Four yrs after the establishment of the artificial reefs, microphytobenthos abundance was twice as high in reef plots (1.7 ± 0.1 μg chl-a cm-2) compared to control plots (0.9 ± 0.1 μg chl-a cm-2). The accumulation of periphyton on glass periphytometers was four times higher in artificial reef plots (200.1 ± 45.8 mg chl-a m-2) compared to control plots (54.8 ± 6.8 mg chl-a m-2). The seagrass beds surrounding the artificial reefs changed rapidly, from a sparse Thalassia testudinum (Banks & Soland. ex König) dominated community, which persisted at control plots, to a community dominated by Halodule wrightii (Ascherson). Such changes mirror the changes induced in experimentally fertilized seagrass beds in Florida, strongly suggesting that the aggregations of animals attracted by artificial reefs concentrated nutrients in this oligotrophic seascape, favoring the growth of fast-growing primary producers like microphytobenthos and periphyton, and changing the competitively dominant seagrass from slow-growing T. testudinum to faster-growing H. wrightii in the vicinity of the reefs.

Leaf Gas Exchange and Nutrient Use Efficiency Help Explain the Distribution of Two Neotropical Mangroves under Contrasting Flooding and Salinity

Rhizophora mangle and Laguncularia racemosa cooccur along many intertidal floodplains in the Neotropics. Their patterns of dominance shift along various gradients, coincident with salinity, soil fertility, and tidal flooding. We used leaf gas exchange metrics to investigate the strategies of these two species in mixed culture to simulate competition under different salinity concentrations and hydroperiods. Semidiurnal tidal and permanent flooding hydroperiods at two constant salinity regimes (10 g L−1 and 40 g L−1) were simulated over 10 months. Assimilation ( ), stomatal conductance ( ), intercellular CO2 concentration ( ), instantaneous photosynthetic water use efficiency (PWUE), and photosynthetic nitrogen use efficiency (PNUE) were determined at the leaf level for both species over two time periods. Rhizophora mangle had significantly higher PWUE than did L. racemosa seedlings at low salinities; however, L. racemosa had higher PNUE and and, accordingly, had greater intercellular CO2 (calculated) during measurements. Both species maintained similar capacities for A at 10 and 40 g L−1 salinity and during both permanent and tidal hydroperiod treatments. Hydroperiod alone had no detectable effect on leaf gas exchange. However, PWUE increased and PNUE decreased for both species at 40 g L−1 salinity compared to 10 g L−1. At 40 g L−1 salinity, PNUE was higher for L. racemosa than R. mangle with tidal flooding. These treatments indicated that salinity influences gas exchange efficiency, might affect how gases are apportioned intercellularly, and accentuates different strategies for distributing leaf nitrogen to photosynthesis for these two species while growing competitively.

An investigation of the molecular interactions between statins and bacterial pathogens, and their combined impact on the human immune system

Statins are a class of drug that inhibits cholesterol biosynthesis, and are used to treat patients with high serum cholesterol levels. They exert this function by competitively binding to the enzyme 3-hydroxy-3-methylglutaryl-CoenzymeA reductase (HMGR), which catalyses the formation of mevalonate, a rate-limiting step in cholesterol biosynthesis. In addition, statins have what are called “pleiotropic effects”, which include the reduction of inflammation, immunomodulation, and antimicrobial effects. Statins can also improve survival of patients with sepsis and pneumonia. Cystic fibrosis (CF) is the most common recessive inherited disease in the Caucasian population, which is characterised by factors including, but not limited to, excessive lung inflammation and increased susceptibility to infection. Therefore, the overall objective of this study was to examine the effects of statins on CFassociated bacterial pathogens and the host response. In this work, the prevalence of HMGR was examined in respiratory pathogens, and several CF-associated pathogens were found to possess homologues of this enzyme. HMGR homology was analysed in Staphylococcus aureus, Burkholderia cenocepacia and Streptococcus pneumoniae, and the HMGR of B. cenocepacia was found to have significant conservation to that of Pseudomonas mevalonii, which is the most widely-characterised bacterial HMGR. However, in silico analysis revealed that, unlike S. aureus and S. pneumoniae, B. cenocepacia did not possess homologues of other mevalonate pathway proteins, and that the HMGR of B. cenocepacia appeared to be involved in an alternative metabolic pathway. The effect of simvastatin was subsequently tested on the growth and virulence of S. aureus, B. cenocepacia and S. pneumoniae. Simvastatin inhibited the growth of all 3 species in a dose-dependent manner. In addition, statin treatment also attenuated biofilm formation of all 3 species, and reduced in vitro motility of S. aureus. Interestingly, simvastatin also increased the potency of the aminoglycoside antibiotic gentamicin against B. cenocepacia. The impact of statins was subsequently tested on the predominant CF-associated pathogen Pseudomonas aeruginosa, which does not possess a HMGR homologue. Mevastatin, lovastatin and simvastatin did not influence the growth of this species. However, sub-inhibitory statin concentrations reduced the swarming motility and biofilm formation of P. aeruginosa. The influence of statins was also examined on Type 3 toxin secretion, quorum sensing and chemotaxis, and no statin effect was observed on any of these phenotypes. Statins did not appear to have a characteristic effect on the P. aeruginosa transcriptome. However, a mutant library screen revealed that the effect of statins on P. aeruginosa biofilm was mediated through the PvrR regulator and the Cup fimbrial biosynthesis genes. Furthermore, proteomic analysis demonstrated that 6 proteins were reproducibly induced by simvastatin in the P. aeruginosa swarming cells. The effect of statins on the regulation of the host-P. aeruginosa immune response was also investigated. Statin treatment increased expression of the pro-inflammatory cytokines IL-8 and CCL20 in lung epithelial cells, but did not attenuate P. aeruginosa-mediated inflammatory gene induction. In fact, simvastatin and P. aeruginosa caused a synergistic effect on CCL20 expression. The expression of the transcriptional regulators KLF2 and KLF6 was also increased by statins and P. aeruginosa, with the induction of KLF6 by simvastatin proving to be a novel effect. Interestingly, both statins and P. aeruginosa were capable of inducing alternative splicing of KLF6. P. aeruginosa was found to induce KLF6 alternative splicing by way of the type 3 secreted toxin ExoS. In addition, a mechanistic role was elucidated for KLF6 in the lung, as it was determined that statin-mediated induction of this protein was responsible for the induction of the host response genes CCL20 and iNOS. Moreover, statin treatment caused a slight increase in infection-related cytotoxicity, and increased bacterial adhesion to cells. Taken together, these data demonstrate that statins can reduce the virulence of CFassociated bacterial pathogens and alter host response effectors. Furthermore, novel statin effectors were identified in both bacterial and host cells.

A Bayesian Dirichlet-Multinomial Test for Cross-Group Differences

Testing for differences within data sets is an important issue across various applications. Our work is primarily motivated by the analysis of microbiomial composition, which has been increasingly relevant and important with the rise of DNA sequencing. We first review classical frequentist tests that are commonly used in tackling such problems. We then propose a Bayesian Dirichlet-multinomial framework for modeling the metagenomic data and for testing underlying differences between the samples. A parametric Dirichlet-multinomial model uses an intuitive hierarchical structure that allows for flexibility in characterizing both the within-group variation and the cross-group difference and provides very interpretable parameters. A computational method for evaluating the marginal likelihoods under the null and alternative hypotheses is also given. Through simulations, we show that our Bayesian model performs competitively against frequentist counterparts. We illustrate the method through analyzing metagenomic applications using the Human Microbiome Project data.

The Development of a Hybrid Optimization Algorithm for the Evaluation and Optimization of the Asynchronous Pulse Unit

The effectiveness of an optimization algorithm can be reduced to its ability to navigate an objective function’s topology. Hybrid optimization algorithms combine various optimization algorithms using a single meta-heuristic so that the hybrid algorithm is more robust, computationally efficient, and/or accurate than the individual algorithms it is made of. This thesis proposes a novel meta-heuristic that uses search vectors to select the constituent algorithm that is appropriate for a given objective function. The hybrid is shown to perform competitively against several existing hybrid and non-hybrid optimization algorithms over a set of three hundred test cases. This thesis also proposes a general framework for evaluating the effectiveness of hybrid optimization algorithms. Finally, this thesis presents an improved Method of Characteristics Code with novel boundary conditions, which better characterizes pipelines than previous codes. This code is coupled with the hybrid optimization algorithm in order to optimize the operation of real-world piston pumps.

Partial Cooperation in Location Choice: Salop’s Model with Three Firms

We consider how three firms compete in a Salop location model and how cooperation in location choice by two of these firms affects the outcomes. We con- sider the classical case of linear transportation costs as a two-stage game in which the firms select first a location on a unit circle along which consumers are dispersed evenly, followed by the competitive selection of a price. Standard analysis restricts itself to purely competitive selection of location; instead, we focus on the situation in which two firms collectively decide about location, but price their products competitively after the location choice has been effectuated. We show that such partial coordination of location is beneficial to all firms, since it reduces the number of equilibria significantly and, thereby, the resulting coordination problem. Subsequently, we show that the case of quadratic transportation costs changes the main conclusions only marginally.

PROPOSAL OF AN EMPIRICAL MODEL FOR SUPPLIERS SELECTION

The problem of selecting suppliers/partners is a crucial and important part in the process of decision making for companies that intend to perform competitively in their area of activity. The selection of supplier/partner is a time and resource-consuming task that involves data collection and a careful analysis of the factors that can positively or negatively influence the choice. Nevertheless it is a critical process that affects significantly the operational performance of each company. In this work, trough the literature review, there were identified five broad suppliers selection criteria: Quality, Financial, Synergies, Cost, and Production System. Within these criteria, it was also included five sub-criteria. Thereafter, a survey was elaborated and companies were contacted in order to answer which factors have more relevance in their decisions to choose the suppliers. Interpreted the results and processed the data, it was adopted a model of linear weighting to reflect the importance of each factor. The model has a hierarchical structure and can be applied with the Analytic Hierarchy Process (AHP) method or Simple Multi-Attribute Rating Technique (SMART). The result of the research undertaken by the authors is a reference model that represents a decision making support for the suppliers/partners selection process.