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Continuous glucose monitoring (CGM) devices offer diabetes patients a convenient approach to assist in controlling blood glucose levels. A prototype CGM has been developed that uses the emission profile of a polarity-sensitive fluorophore (acrylodan) conjugated to a glucose/galactose-binding protein (SM4-AC) to measure the concentration of glucose in vivo. During development, a decrease in the devices signal intensity was observed in vivo over time, which was postulated to be result of oxidative degradation of SM4-AC. A comprehensive physicochemical analysis of SM4-AC was pursued to identify potential mechanisms of signal intensity loss in this CGM during in vitro forced oxidation studies. An assessment of the structural integrity and conformational stability of SM4-AC indicated a relatively decreased polarity and lower tertiary structure stability compared to unconjugated protein (SM4). The stability and polarity of SM4-AC was also altered in the presence of H2 O2 . Furthermore, a time-dependent loss in the fluorescence signal of SM4-AC was observed when incubated with H2 O2 . An LC-MS peptide mapping analysis of these protein samples indicated that primarily two Met residues in SM4-AC were susceptible to oxidation. When these two residues were genetically altered to an amino acid not prone to oxidation, the glucose binding ability of the protein was retained and no loss of acrylodan fluorescence was observed in the presence of H2 O2 . Genetic alteration of these two residues is proposed as an effective approach to increase the long-term stability of SM4-AC within this prototype CGM in vivo.

We demonstrate that the electrochemical signa- tures of graphene screen-printed electrodes towards hy- drazine are not due to the reported benefits of graphene per se but rather it is the metallic impurities which can.

The pursuit of ultraflexible sensors has arisen from the recent implementation of electrochemical sensors into wearable clothing where extensive mechanical stress upon the sensing platform is likely to occur. Such scenarios have witnessed screen-printed electrodes being incorporated into the waistband of undergarments for the determination of key analytes while others have reported incorporation into a neoprene wetsuit. In these conformations, the substrates which the sensors are printed upon need to be ultraflexible and capable of withstanding extensive individual mechanical stress. Therefore the composition, thickness and its combination of screen-printed ink require extensive consideration. A common short-coming within the field of screen-printed derived sensors is the lack of consideration towards the substrate material employed, and is rather in favour of the development of new electrode geometries and screen-printing inks. In this paper we explore the screen-printing of graphite based electroanalytical sensing platforms onto graphic paper commonly used in house-hold printers, and for the first time both tracing paper and ultraflexible polyester-based substrates are used. These sensors are electrochemically benchmarked with the redox probes hexaammine-ruthenium(III) chloride and potassium ferrocyanide(II). The effect of mechanical contortion upon two types of electrode substrates is also performed where it was found that these ultraflexible based polyester-based electrodes are superior to the previously reported ultraflexible paper electrodes since they can withstand extensive mechanical contortion, yet they still give rise to useful electrochemical performances. Most importantly the ultraflexible polyester electrodes do not suffer from capillary action as observed in the case of paper-based sensors causing the solution to wick-up the electrode towards the electrical connections resulting in electrical shorting, therefore compromising the electrochemical measurement; as such this new substrate can be used as a replacement for paper-based substrates and yet still be resilient to extreme mechanical contortion. A new configuration is also explored using these electrode substrate supports where the working carbon electrode contains the electrocatalyst, cobalt(II) phthalocyanine (CoPC), and is benchmarked towards the electroanalytical sensing of the model analytes citric acid and hydrazine which demonstrate excellent sensing capabilities in comparison to previously reported screen-printed electrodes.

Surfactants are routinely used in the production of graphene and additionally in their solubilisation with the aim of reducing the likelihood of coalescing. We demonstrate that surfactants, which are an inherent property of graphene, are a major contribution to the electrochemical performance. Using well characterised commercially available graphene we demonstrate that the surfactant may be detrimental in electrochemical processes, for example in the electrochemical oxidation of NADH, used prolifically as the basis of over 300 biosensors, and in the electrochemical oxidation of acetaminophen, an analgesic and antipyretic drug which requires routine monitoring in a plethora of areas. The use of control experiments in the form of surfactant modified carbon electrodes is particularly encouraged in de-convoluting the origin of the electrochemical response of graphene modified electrodes.

A kinetic model developed to investigate surface-initiated photoiniferter-mediated photopolymerization (SI-PMP) and parameterized using experimental thickness data from SI-PMP of methyl methacrylate is used to examine chain extension by reinitiation. Specifically, the effects of light intensity, concentration of an added deactivator, tetraethylthiuram disulfide (TED), and initial photoiniferter (PI) concentration on the reinitiation ability of surface-tethered PMMA layers is examined in detail. The simulations show that while increases in [TED] and decreases in light intensity affect overall rates of PMMA layer growth in a similar fashion, their effect on reinitiation ability of PMMA layers is significantly different: reinitiation ability increases with increasing [TED] but it is not improved by decreases in light intensity. Simulations also suggest that polymer layers synthesized in the presence of TED have a greater tendency to form surface-tethered block copolymers upon reinitiation compared with polymer layers synthesized without TED and at lower light intensity. While both [PI] and [TED] affect the reinitiation ability, the effect of [TED] on reinitiation ability is identical at a given [TED]/[PI] ratio for all PI and TED concentrations tested. These findings obtained from the rate-based model are instrumental in delineating strategies for creating tethered block copolymer layers or mixed brushes by SI-PMP.

This special issue is dedicated to Operations Management (OM) in Asia. A requirement for the special issue articles is that they have content related to the effects of national culture on OM. Here, the OM literature is combined with work from Anthropology and Women's Studies to provide a wide view of the effects of various Asian cultures on OM. The basic premise is that OM decisions may need to take culture into account: some OM practices are altered or precluded by culture, while others are more effective in some cultures than others. Numerous examples are provided involving quality management, shift scheduling, revenue management, facility location, layout, supply chain strategies, and other areas.

We consider a single product, single level, stochastic master production scheduling (Mps) model where decisions are made under rolling planning horizons. Outcomes of interest are cost, service level, and schedule stability. The subject of this research is the Mps control system: the method used in determining the amount of stock planned for production in each time period. Typically, Mps control systems utilize a single buffer stock. Here, two Mps dual-buffer stock systems are developed and tested by simulation. We extend the data envelopment analysis (dea) methodology to aid in the evaluation of the simulation results, where Dea serves to increase the scope of the experimental design. Results indicate that the dual-buffer control systems outperform existing policies.

Data envelopment analysis (dea) has become an increasingly popular method to measure performance for service firms with multiple sites. DEA is superior to many traditional methods for firms that have multiple goals. The promise of DEA is that the complex, multi-objective problem of performance measurement can be reduced to a single number. Unfortunately, the practice of DEA often belies the promise. Misconceptions concerning the purpose and implementation of DEA can cause DEA applications to be less than successful. Here, the technique is explained, and a guide to the implementation of DEA is proposed, utilizing DEA studies of retail bank branches.

Surface-initiated photoiniferter-mediated photopolymerization (SI-PMP) in presence of tetraethylthiuram disulfide is used to directly synthesize surface-grafted poly(methacrylic acid)-block-poly(N-isopropylacrylamide) (PMAA-b-PNIPAM) layers. The response of these PMAA-b-PNIPAM bi-level brushes to changes in pH, temperature and ionic strength is investigated by using in-situ multi-angle ellipsometry to measure changes in solvated layer thickness. As expected for a block copolymer architecture, PMAA blocks swell as pH is increased, with the maximum change in the thickness occurring near pH = 5, and PNIPAM blocks exhibit lower critical solution temperature (LCST) behavior, marked by a broad transition between swollen and collapsed states. The response of the bi-level brushes to changes in added salt at constant pH is complex, as the swelling behaviors of both the weak polyelectrolyte, PMAA, and thermoresponsive PNIPAM are affected by changes in ionic strength. This work demonstrates not only the robustness of SI-PMP for making novel, bi-level stimuli-responsive brushes, but also the complex links between synthesis, structure, and response of these materials.

Operations Management ( OM) research on organizational culture has to change to be able to inform practice. Currently, organizational culture research in OM is largely confined to narrow topical and methodological niches and culture is most frequently used as an explanatory variable in quantitative, survey-based research. We argue that the relegation of culture to this niche is due to self-imposed methodological blinders that hobble the OM field. We then present four research imperatives to reinvigorate organizational culture research within our field. We urge OM scholars to view culture as a dynamic concept that can be influenced, to adopt alternative methods, to use non-traditional data sources, and to rethink assumptions about dependent variables. We also identify gaps in the current knowledge and new research questions for the OM domain. We conclude that the field of OM could greatly expand its understanding of organizational culture and in so doing greatly improve business practice, but that to do so will require a change in the culture of the operations management research community. [ABSTRACT FROM AUTHOR]

Affinity hydrogels based on poly(ethylene glycol) diacrylate and a metal-ion-chelating ligand, glycidyl methacrylate-iminodiacetic acid, have been developed to systematically decrease protein release rates from hydrophilic tissue engineering scaffolds formed in situ. In the current work, tunable and sustained release of a model protein, hexa-histidine tagged green fluorescence protein (hisGFP), is accomplished by judiciously increasing ligand:protein ratio or replacing low-affinity nickel ions with high-affinity copper ions. Agreement between theoretical predictions of a reaction-diffusion model and experimental measurements confirm metal- ion-mediated sustained protein release from these affinity hydrogels is governed by equilibrium protein-ligand binding affinity (dissociation constant, Kd) as well as protein-ligand dissociation kinetics (protein debinding rate constant, k off). The former dictates the release rate in the early period of protein release while the latter determines the long-term sustained release effect. While metal-ion affinity binding has been widely used for various purposes including protein purification and surface patterning, this is the first report describing its application in systematically controlling protein release from hydrophilic PEG networks suitable for cell encapsulation. By using ligands with proper binding kinetic constants (Kd and k off), localized protein delivery can be sustained over clinically relevant timescales while maintaining a favorable environment for cell encapsulation and viability.

Services are now a larger portion of the economy than manufacturing for every nation on Earth, and services are an overwhelming portion of Western economies. While decision-making research has begun responding to this change, much of the scholarly work still addresses manufacturing issues. Particularly revealing is the field of operations management (OM), in which the proportion of manuscripts dedicated to services has been estimated at 3%, 6%, and 7.5% by various authors. We investigate several possible reasons for the neglect of services in research, including the difficulty in defining services, viewing services as derivative activities, a lack of defined processes, a lack of scale in services, and the effect of variability on service performance. We argue that times have changed, and none of these reasons is valid anymore. We sound the warning that failure to emphasize services in our research and teaching may signal the decline of the discipline. We note the proportion of OM faculty in business schools has shrunk in the past 10 years. Finally, we examine a selection of service research agendas and note several directions for high-impact, innovative research to revitalize the decision sciences. With practitioners joining the call for more research in services, the academic community has an exciting opportunity to embrace services and reshape its future.

The offshoring and outsourcing of service work from high-wage to low-wage countries has received considerable exposure in the popular press. Some have claimed that virtually all services that can be electronically transmitted should be offshored due to the extreme labor rate differentials. Relatively little work has actually been offshored to date, making empirical assessment difficult. Here, a normative model of the appropriate role of offshoring is proposed. We present a strategic contingency model, to be viewed at the process level, intimating that firms with the same processes should come to different solutions regarding these decisions.

The degradation of polymers under ultraviolet (UV) irradiation has been a great concern for biomaterial and agricultural applications. The major objective of this research was to study the effect of UV irradiation on the representative bulk and surface properties of poly (L-lactide) (PLA) films. Two UV sources with different spectral outputs and intensities were chosen so that one of them could be used for surface modification and the other could be used for UV sterilization of the PLA films. The results established that the molecular weight of PLA decreased significantly during irradiation from the photografting lamp under atmospheric conditions. Irradiation through a Pyrex container was shown to minimize polymer degradation during UV exposure from the photografting lamp. The PLA films UV-irradiated under the sterilization lamp for 12 h revealed a similar reduction in the molecular weight and no change in the surface hydrophilicity. However, significantly less photodegradation was observed under the sterilization lamp when the samples were held in a Pyrex container. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007

Poly(L-lactide) (PLL) has been used as a bioabsorbable material in the medical and pharmaceutical fields. The unmodified hydrophobic PLL surface generally has low cell affinity; thus, modification of PLL film surface properties is necessary to improve its use as a biomaterial. Our surface modification method involved the use of photografting and typical wet chemistry to create branched architectures containing amine functionalities on the periphery of the grafted layers. Amine (-NH2) groups were first introduced on the PLL film surface by photoinduced grafting of 4,4'-diaminobenzophenone and the grafted branched architectures were created by subsequent reactions with succinic acid and tris(2-aminoethyl) amine. The resulting film surface was analyzed using contact angle goniometry and X-ray photoelectron spectroscopy. MC3T3 fibroblasts were cultured on unmodified PLL film and PLL films grafted with the branched structures and the films were subsequently analyzed by optical microscopy. The contact angle goniometry results showed an initial decrease and subsequent plateau in the water contact angles for the PLL films with each successive generation of the branched architectures. The X-ray photoelectron spectroscopy data provided insight into the structure of the grafted layer and revealed an increase in the nitrogen content with each generation. Optical micrographs showed enhanced cell attachment and viability on the surface-modified PLL films.

The major objective of this research was to modify the surface characteristics of poly(L-lactide) (PLA) by grafting a combination of hydrophilic polymers to produce a continuum of hydrophilicity. The PLA film was solvent cast, and the film surfaces were activated by ultra violet (UV) irradiation. A single monomer or combination of two monomers, selected from vinyl acetate (VAc), acrylic acid (AA), and acrylamide (AAm), were then grafted to the PLA film surface using a UV induced photopolymerization process. The film surfaces resulting from each reaction step were analyzed using ATR-FTIR spectroscopy and contact angle goniometry. Results showed that AAm dominated the hydrophilicity of the film surface when copolymerized with VAc or AA, while the water contact angles for PLA films grafted with poly(vinyl acetate-co-acrylic acid) varied more gradually with feed composition. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 6534-6543, 2006

A statistical-co-kinetic model has been developed to predict effects of hydrolytic or enzymatic degradation on the macroscopic properties of hydrogels formed through Michael-type addition reactions. Important parameters accounted for by the theoretical calculations are bond cleavage kinetics, microstructural network characteristics such as macromer functionality and crosslinking efficiency, and detailed analysis of degradation products. Previous work indicated the validity of this modeling approach for predicting swelling behavior of hydrolytically degradable gels during early stages of degradation and the quantitative dependence of gel degradation on kinetic and structural parameters. The theoretical methodology is extended in the current work to predict release of covalently bound proteins from the network via labile bonds. Release studies of a network-bound fluoroscopic probe allow validation of model degradation parameters and indicate that macromer functionalization and network crosslinking efficiency can be appropriately tailored to achieve desired swelling profiles and protein release rates over the lifetime of the degradable gel. The effects of these network parameters on the timing of gel dissolution and the protein release that occurs during this phase of degradation are also identified, highlighting the utility of the developed model as a comprehensive tool for optimizing degradable hydrogels as matrices for drug delivery and tissue regeneration.

Dendritic cells (DC) are potent immunostimulatory cells facilitating antigen transport to lymphoid tissues and providing efficient stimulation of T cells. A series of experimental studies in mice demonstrated that cytotoxic T lymphocytes (CTL) can be efficiently induced by adoptive transfer of antigen-presenting DC. However, the success of DC-based immunotherapeutic treatment of human cancer, for example, is still limited because the details of the regulation and kinetics of the DC-CTL interaction are not yet completely understood. Using a combination of experimental mouse studies, mathematical modeling, and nonlinear parameter estimation, we analyzed the population dynamics of DC-induced CTL responses. The model integrates a predator-prey-type interaction of DC and CTL with the non-linear compartmental dynamics of T cells. We found that T cell receptor avidity, the half-life of DC, and the rate of CTL-mediated DC-elimination are the major control parameters for optimal DC-induced CTL responses. For induction of high avidity CTL, the number of adoptively transferred DC was of minor importance once a minimal threshold of approximately 200 cells per spleen had been reached. Taken together, our study indicates that the availability of high avidity T cells in the recipient in combination with the optimal application regimen is of prime importance for successful DC-based immunotherapy.

1. The recombinant human prostaglandin D(2) (PGD(2)) receptor, hCRTH2, has been expressed in HEK293(EBNA) and characterized with respect to radioligand binding and signal transduction properties. High and low affinity binding sites for PGD(2) were identified in the CRTH2 receptor population by saturation analysis with respective equilibrium dissociation constants (K(D)) of 2.5 and 109 nM. This revealed that the affinity of PGD(2) for CRTH2 is eight times less than its affinity for the DP receptor. 2. Equilibrium competition binding assays revealed that of the compounds tested, only PGD(2) and several related metabolites bound with high affinity to CRTH2 (K(i) values ranging from 2.4 to 34.0 nM) with the following rank order of potency: PGD(2)>13,14-dihydro-15-keto PGD(2)>15-deoxy-Delta(12,14)-PGJ(2)>PGJ(2)>Delta(12)-PGJ(2)>15(S)-15 methyl-PGD(2). This is in sharp contrast with the rank order of potency obtained at DP : PGD(2)>PGJ(2)>Delta(12)-PGJ(2)>15-deoxy-Delta(12,14)-PGJ(2) >>>13,14-dihydro-15-keto-PGD(2). 3. Functional studies demonstrated that PGD(2) activation of recombinant CRTH2 results in decrease of intracellular cAMP in a pertussis toxin-sensitive manner. Therefore, we showed that CRTH2 can functionally couple to the G-protein G(alphai/o). PGD(2) and related metabolites were tested and their rank order of potency followed the results of the membrane binding assay. 4. By Northern blot analysis, we showed that, besides haemopoietic cells, CRTH2 is expressed in many other tissues such as brain, heart, thymus, spleen and various tissues of the digestive system. In addition, in situ hybridization studies revealed that CRTH2 mRNA is expressed in human eosinophils. Finally, radioligand binding studies demonstrated that two eosinophilic cell lines, butyric acid-differentiated HL-60 and AML 14.3D10, also endogenously express CRTH2.

This paper presents an overview of the new issues and research opportunities related to four service operations design topics—the design of retail and e-tail service processes, design of service processes involving waiting lines and workforce staffing, service design for manufacturing, and re-engineering service processes. All four topics are motivated by new technologies (particularly web-based technologies) and require a multi-disciplinary approach to research. For each topic, the paper presents an overview of the topic, the relevant frameworks, and a discussion of the research opportunities.

Seeral macroscopic properties of degrading poly lactic acid -b-poly ethylene glycol - () ( ) b-poly lactic acid PLA-b-PEG-b-PLA hydrogels were compared to one another as functions of degradation time. The specific hydrogel properties measured were the com- () ( ) pressie modulus K , theolumetric swelling ratio Q , and the normalized compres- ( 1r3 ) sie modulus K s KQ . Their comparisons were used to ealuate the applica- NORM bility of fundamental thermodynamic theories deeloped for nondegradable hydrogels on a degradable system. The equations predict scaling factors of y2, y5r3, and 6r5 for the dependence of K on Q, K on Q, and K on K , respectiely. These impor- NORM N ORM tant experimental data for a degrading hydrogel system initially show good agreement with the scaling predictions. Further examination, howeer, reeals the scaling factors to change oer the course of the degradation process. These changes are attributed, at least in part, to the changing chemical, mechanical, and ionic properties of the degrading copolymer networks.

This study demonstrates the localization of the prostaglandin (PG)D2 receptor (DP) within the mucous-secreting globlet cells of the human colon by in situ hybridization, which suggests a role for DP in mucous secretion. Selective high affinity ligands were used, therefore, to evaluate DP regulation of mucous secretion in LS174T human colonic adenocarcinoma cells. The expression of hDP in LS174T cells was confirmed at the mRNA level by reverse transcriptase-polymerase chain reaction, and at the protein level by radioligand binding assays and signal transduction (cyclic AMP accumulation) assays. PGD2 and the highly selective DP-specific agonist L-644,698 ((4-(3-(3-(3-hydroxyoctyl)-4-oxo-2-thiazolidinyl) propyl) benzoic acid) (racemate)), but not PGE2 competed for [3H]-PGD2-specific binding to LS174T cell membranes (Ki values of 0.4 nM and 7 nM, respectively). The DP-specific agonists PGD2, PGJ2, BW245C (5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropylhydantoin)), and L-644,698 showed similar potencies in stimulating cyclic AMP accumulation (EC50 values: 45–90 nM) and demonstrated the expected rank order of potency. PGE2 also elicited cyclic AMP production in this cell line (EC50 value: 162 nM). The activation of cyclic AMP production by PGD2 and L-644,698, but not PGE2, was inhibited by the selective DP antagonist BW A868C. Thus, PGD2 and L-644,698 act through hDP in LS174T cells. PGD2, L-644,698 and PGE2 (an established mucin secretagogue) potently stimulated mucin secretion in LS174T cells in a concentration-dependent manner (EC50

A potential retail operations strategy is to have a “dense” store. That is, a store that combines high product variety with a small footprint. Retail management desires smaller stores to provide the strategic benefits of convenience and speed to customers, but desires larger stores to provide high product variety. Noting the benefits of smaller, more numerous stores, several retailers well known for their extremely large store size recently have begun experimenting with a small store format. Traditional retail inventory management policies, however, have difficulty combining high variety and small store size. Here, the potential advantages of the dense store type are explored. To facilitate this exploration, inventory policies are developed to help manage small stores by increasing their product density. Results based on grocery industry data indicate that the heuristics compare favorably to optimality and permit the dense store concept to potentially achieve substantial gains compared to current practice.

1 We characterized the regulation of cyclooxygenase-2 (COX-2) at the mRNA, protein and mediator level in two rat models of acute inflammation, carrageenan-induced paw oedema and mechanical hyperalgesia. 2 Carrageenan was injected in the hind paw of rat at low (paw oedema) and high doses (hyperalgesia). COX-2 and prostaglandin E2 (PGE2) levels were measured by RT-PCR and immunological assays. We also determined the distribution of COX-2 by immunohistochemistry. 3 The injection of carrageenan produced a significant and parallel induction of both COX-2 and PGE2. This induction was significantly higher in hyperalgesia than in paw oedema. This was probably due to the 9 fold higher concentration of carrageenan used to provoke hyperalgesia. 4 Immunohistochemical examination showed COX-2 immunoreactivity in the epidermis, skeletal muscle and inflammatory cells of rats experiencing hyperalgesia. In paw oedema however, only the epidermis showed positive COX-2 immunoreactivity. 5 Pretreatment with indomethacin completely abolished the induction of COX-2 in paw oedema but not in hyperalgesia. 6 These results suggest that multiple mechanisms regulate COX-2 induction especially in the more severe model. In carrageenan-induced paw oedema, prostanoid production have been linked through the expression of the COX-2 gene which suggest the presence of a positive feedback loop mechanism.

1. A human embryonic kidney cell line [HEK 293(EBNA)] stably expressing the human recombinant prostaglandin D2 (PGD2) receptor (hDP) has been characterized with respect to radioligand binding and signal transduction properties by use of prostanoids and prostanoid analogues. Radioligand binding studies included saturation analyses, the effects of nucleotide analogues, the initial rate of ligand-receptor association and equilibrium competition assays. In addition, adenosine 3':5'-cyclic monophosphate (cyclic AMP) generation in response to ligand challenge was also measured, as this is the predominant hDP signalling pathway. 2. L-644,698 ((4-(3-(3-(3-hydroxyoctyl)-4-oxo-2-thiazolidinyl) propyl) benzoic acid) (racemate)) was identified as a novel ligand having high affinity for hDP with an inhibitor constant (Ki) of 0.9 nM. This Ki value was comparable to the Ki values obtained in this study for ligands that have previously shown high affinity for DP: PGD2 (0.6 nM), ZK 110841 (0.3 nM), BW245C (0.4 nM), and BW A868C (2.3 nM). 3. L-644,698 was found to be a full agonist with an EC50 value of 0.5 nM in generating cyclic AMP following activation of hDP. L-644,698 is, therefore, comparable to those agonists with known efficacy at the DP receptor (EC50): PGD2 (0.5 nM), ZK 110841 (0.2 nM) and BW245C (0.3 nM). 4. L-644,698 displayed a high degree of selectivity for hDP when compared to the family of cloned human prostanoid receptors: EP1 (> 25,400 fold), EP2 (approximately 300 fold), EP3-III (approximately 4100 fold), EP4 (approximately 10000 fold), FP (> 25,400 fold), IP (> 25,400 fold) and TP (> 25,400 fold). L-644,698 is, therefore, one of the most selective DP agonists as yet described. 5. PGJ2 and delta12-PGJ2, two endogenous metabolites of PGD2, were also tested in this system and shown to be effective agonists with Ki and EC50 values in the nanomolar range for both compounds. In particular, PGJ2 was equipotent to known DP specific agonists with a Ki value of 0.9 nM and an EC50 value of 1.2 nM.

Consider multiple companies operating as a serial supply chain. Within this environment, end users form the demand for the last company in the supply chain, but the demand for upstream companies is formed by the companies in the immediate downstream supply chain link. It has been shown that demand seasonality and forecast error can increase as we proceed up the supply chain. These demand distortions, called the “bullwhip” effect, create inefficiencies for upstream firms. This work seeks to identify the magnitude of the problem by establishing an empirical lower bound on the profitability impact of the bullwhip effect. Results indicate that the importance of the bullwhip effect to a firm differs greatly depending on the specific business environment. Given appropriate conditions, however, eliminating the bullwhip effect can increase product profitability by 10–30%.

Faculty of Science and Engineering, School of Chemistry and the Environment, Division of Chemistry and Environmental Science,Manchester Metropolitan University, Chester Street, Manchester M15GD, Lancs, UKtel: ++(0)1612471196; fax: ++(0)1612476831Website: www.craigbanksresearch.com*e-mail: c.banks@mmu.ac.ukReceived: June 13, 2013Accepted: August 15, 2013Published online: September 18, 2013AbstractThe influence of mechanical contortion upon the electrochemical performance of screen-printed graphite paper-based electroanalytical sensing platforms is evaluated and contrasted with traditionally employed polymeric basedscreen-printed graphite sensors. Such a situation of implementation can be envisaged for the potential sensing of an-alytes on the skin where such sensors are based, for example in clothing where mechanical contortion, viz, bendingwill occur, and as such, its effect upon electrochemical sensors is of both fundamental and applied importance. Theeffect of mechanical contortion or stress upon electrochemical behaviour and performance is of screen printed sen-sors is explored. Comparisons are made between both paper- and polymeric- based sensing platforms that are evalu-ated towards the sensing of the well characterised electrochemical probes potassium ferrocyanide(II), hexaammine-ruthenium(III) chloride and nicotinamide adenine dinucleotide (NADH). It is determined that the paper-based sen-sors offer greater resilience in terms of electrochemical performance after mechanical stress. We gain insights intothe role played by both the effect of the time of mechanical contortion and additionally the potentially detrimentaleffects of repeated contortion are explored. These unique paper-based sensors hold promise for widespread applica-tions where flexible and ultra-low cost sensors are required such as applications into medical devices were ultra-lowcost sensors are a pre-requisite, but also for utilisation within applications which require the implementation ofultra-flexible electroanalytical sensing platforms such as in the case of wearable sensors, whilst maintaining usefulelectrochemical performances.Keywords: Ultra flexible substrates, Paper-based electrochemical sensors, Screen printing, Mechanical stress onelectrochemical sensorsDOI: 10.1002/elan.201300274Supporting Information for this article is available on the WWW under http://dx.doi.org/10.1002/elan.201300274

Functional cDNA clones coding for three isoforms of the human prostaglandin E receptor EP3 subtype have been isolated from kidney and uterus cDNA libraries. The three isoforms, designated hEP3-I, hEP3-II and hEP3-III, have open reading frames corresponding to 390, 388 and 365 amino acids, respectively. They differ only in the length and amino acid composition of their carboxy-terminal regions, beginning at position 360. The human EP3 receptor has seven predicted transmembrane spanning domains and therefore belongs to the G-protein-coupled receptor family. The rank order of potency for prostaglandins and related analogs in competition for [3H]PGE2 specific binding to membranes prepared from transfected COS cells was comparable for all three isoforms, and as predicted for the EP3 receptor, with PGE2 = PGE1 >> PGF2 alpha = iloprost > PGD2 >> U46619. In addition, the EP3-selective agonist MB28767 was a potent competing ligand with an IC50 value of 0.3 nM, whereas the EP1-selective antagonist AH6909 gave IC50 values of 2-7 microM and the EP2-selective agonist butaprost was inactive. In summary, we have cloned three isoforms of the human EP3 receptor having comparable ligand binding properties.

1-(2,4-Dichlorophenyl)-2-phenylpropen-1-one (2) is identified as a potent antibacterial agent. A compound, 2-chloro-1-(2,4-dichlorophenyl)-3-(1H-imidazol-1-yl)-2-phenylpropan++ +-1-one (5) has been designed with the intention of its acting as a pro-drug, liberating the lethal species 2 specifically within the target anaerobic bacterial cell following bioreduction by bacterial ferredoxin or related electron transfer proteins. The synthesis and biological activity of 5 is described and compared with the activities of the analogous alpha-bromo ketone 6 and alpha-fluoro ketone 7. Synthesis of 6, 7, and the corresponding alpha-hydroxy ketone 11 is also described.

Structure-activity studies leading to the discovery of a new series of non-quinoline cysLT 1 receptor (LTD 4 receptor) antagonists are described. These studies demonstrated that the quinoline ring system of montelukast ( 5 ) may be replaced by an appropriately substituted thienopyridine system, yielding potent compounds. Two other molecular features of montelukast, the terminal phenyl ring substitution and the vinyl link, were also reevaluated. These studies led to the identification of 1 (L-740,515) , a compound with optimized in vitro and in vivo biological profiles.

A new class of potent ligand for the human peripheral cannabinoid (hCB 2 ) receptor is described. Two indole analogs 13 and 17 exhibited nanomolar potencies (K i ) with good selectivity for the hCB 2 receptor over the human central cannabinoid (hCB 1 ) receptor.

To gain insight into the role of prostanoids in human kidney function, we examined the distribution of cyclooxygenase (COX) 1 and COX-2 by immunofluorescence and immunohistochemistry in human kidneys from adults of various age groups. COX-1 was detected in the collecting ducts, thin loops of Henle and portions of the renal vasculature. COX-2 was detected in the renal vasculature, medullary interstitial cells, and the macula densa. In addition, COX-2 immunoreactivity was noted in afferent arteries and the macula densa of the renal cortex and was more evident in the kidneys of older adults.

Synenkephalin (SYN), the nonopioid amino-terminal portion of proenkephalin (PRO), is stable and well conserved in mammals and therefore a promising marker for PRO systems. We immunized rabbits with synthetic [Tyr63]SYN(63-70)-octapeptide, coupled by glutaraldehyde to bovine serum albumin. In radioimmunoassay (RIA) using antiserum no. 681, [Tyr63]SYN(63-70)-octapeptide as standard, and 125I-[Tyr63]SYN(63-70)-octapeptide as tracer, the IC50 was approximately 51 fmol/100-microliters sample at equilibrium or 12 fmol/100 microliters in disequilibrium, and the sensitivity was approximately 3 fmol/100 microliters. Cross-reactivity of the assay was 100% with [Cys63]SYN(63-70)-octapeptide and with bovine adrenal 8.6-kilodalton peptide digested with trypsin and carboxypeptidase B, but less than 0.1% with transforming growth factor-alpha, less than or equal to 2 x 10(-6) with Leu-Leu-Ala [SYN(68-70)-tripeptide], and much less than 10(-6) with all other peptides tested. Therefore in RIA this antiserum is specific for the free carboxyl terminus of SYN. Because the peptide detected after enzyme digestion is the complete SYN(63-70)-octapeptide, we refer to the RIA as an assay for SYN(63-70). Tissue extracts were made in 1 M acetic acid, dried, reconstituted in Tris-CaCl2, and digested sequentially with trypsin plus carboxypeptidase B. Extracts from bovine corpus striatum gave SYN(63-70) RIA dilution curves parallel to the standard curve both before and after digestion. Digestion increased the amount of immunoreactive SYN(63-70) in striatum by a factor of 1.5-2.0. The ratio of total immunoreactive [Met5]enkephalin to total immunoreactive SYN(63-70) (after sequential digestion) was approximately 6:1. At least 90% of the immunoreactive SYN(63-70) in extracts of bovine caudate nucleus eluted from Sephadex G-100 with an apparent molecular weight equal to that of bovine PRO(1-77). Using the new RIA we were able to detect and characterize SYN processing for the first time in extracts of whole rat brain, human globus pallidus, and human pheochromocytoma. Results in these tissues were similar to those in cattle, in that most stored SYN had been processed to a free carboxyl terminus. Since the C-terminal octapeptide of SYN is practically identical in all known mammalian PRO, antiserum no. 681 should be useful for detecting, measuring, and purifying SYN from various mammals, including human beings.

Analogues of PGE(2) wherein the hydroxycyclopentanone ring has been replaced by a lactam have been prepared and evaluated as ligands for the EP(4) receptor. An optimized compound (19a) shows high potency and agonist efficacy at the EP(4) receptor and is highly selective over the other seven known prostaglandin receptors.