203 research outputs found
La cadena de Markov tipo M / G / 1 con transiciones restringidas y su aplicación a colas con llegadas por lotes
No full textWe consider M/G/1-type Markov chains where a transition that decreases the value of the level triggers the phase to a small subset of the phase space. We show how this structure—referred to as restricted downward transitions—can be exploited to speed up the computation of the stationary probability vector of the chain. To this end we define a new M/G/1-type Markov chain with a smaller block size, the G matrix of which is used to find the original chain's G matrix. This approach is then used to analyze the BMAP/PH/1 queue and the BMAP[2]/PH[2]/1 preemptive priority queue, yielding significant reductions in computation time
The M/G/1-type Markov chain with restricted transitions and its application to queues with batch arrivals
No full textAbstract: We consider M/G/1-type Markov chains where a transition that decreases the value of the level triggers the phase to a small subset of the phase space. We show how this structurereferred to as restricted downward transitionscan be exploited to speed up the computation of the stationary probability vector of the chain. To this end we define a new M/G/1-type Markov chain with a smaller block size, the G matrix of which is used to find the original chain's G matrix. This approach is then used to analyze the BMAP/PH/1 queue and the BMAP[2]/PH[2]/1 preemptive priority queue, yielding significant reductions in computation time
Applications of RFID in the pharmaceutical supply chain
No full textL’obiettivo di questa tesi è principalmente quello di mostrare le possibili applicazioni della tecnologia RFID (Radio Frequency Identification) all’interno della supply chain farmaceutica, cercando di comprendere il campo di applicazione di questa tecnologia in un’industria così altamente regolata e complessa come quella farmaceutica.
La tesi è organizzata in tre sezioni; nel primo capitolo si trattano i principi alla base della tecnologia RFID e l’attuale stato dell’arte nella standardizzazione della banda di frequenza utilizzata e nell’hardware. In questa sezione sono poi mostrate le principali applicazioni e nella parte finale i problemi affrontati da un’azienda nell’applicare l’RFID al proprio business.
Il secondo capitolo descrive le parti coinvolte nell’industria farmaceutica, dal produttore al consumatore finale, poi esamina le caratteristiche essenziali della supply chain farmaceutica e gli aspetti chiave e le criticità da affrontare in questo campo per essere efficiente e per consegnare il prodotto al cliente in maniera sicura e consistente.
Infine nell’ultima sezione i due argomenti centrali sono fusi assieme, cercando di esaminare come la tecnologia RFID sia in grado di risolvere i problemi affrontati da tale industria.
Il lavoro non vuole mostrare la tecnologia RFID come una panacea di tutte le problematiche presentate in questa industria, ma vuole cercare di colmare il gap presente in letteratura riguardo le possibili applicazioni di questa tecnologia nell’industria specificata
A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci
No full textThe bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function
Integrated strategic supply chain positioning for SMEs: an empirical study
No full textPurpose - This paper reports on an investigation into the selection and evaluation of a suitable
strategic positioning methodology for SMEs in Singapore.
Findings - This paper illustrates a leading integrated strategic positioning decision making
process, which has been found to be potentially suitable for SMEs in Singapore, and the
process is then applied and evaluated in 2 industrial case studies. Results in the form of
strengths, weaknesses and opportunities are evaluated and discussed in detail, and further
research to improve the process has been identified
Replication Data for: Side-Chain and Ring-Size Effects on Permeability in Artificial Water Channels
No full textArtificial water channels (AWCs) have emerged as a promising framework for stable water permeation, with water transport rates comparable to aquaporins (3.4–40.3 × 108 H2O/channel/s). In this study, we probe the influence of ring-size and side-chain length on the water permeability observed within a class of AWCs termed ligand-appended pillar[n]arenes (LAPs) that have an adjustable ring-size (m) and side-chain length (n). Through all-atom molecular dynamics simulations, we calculate the permeability of these channels using the collective diffusion model and find their permeabilities. We characterize the mechanistic influence of pillar[n]arene ring-size and side-chain length on the channel water permeability by analyzing the characteristics of the internal permeating water-wire and the surrounding channel structure. We observe that water permeability decreases as a function of increasing ring-size due to increases in hydrophilic contacts between the permeating water-wire and the oxygen groups on the channel wall. Further, we observe an increase in water permeability as a function of side-chain length due to increased partitioning of the channel terminal groups into the hydrophilic blocks of the surrounding bilayer. For the LAP6 channel, with increase in side-chain length, the distance between terminal groups increases and leads to an increase in pore size, thereby enhancing water permeability. In the case of LAP5, as side-chain length increases, the channel displays a compensatory effect between tilt and bend angle due to the flexible side-chains. Such flexibility leads to higher terminal group partitioning in the hydrophilic blocks of the bilayer and extends the permeating water-wire. This increase in water-wire length and hydrophilic block access overcomes the nonmonotonic pore size trend in pillar[5]arene channels
Proteomic evaluation and validation of cathepsin D regulated proteins in macrophages exposed to Streptococcus pneumoniae
No full textMacrophages are central effectors of innate immune responses to bacteria. We have investigated how activation of the abundant macrophage lysosomal protease, cathepsin D, regulates the macrophage proteome during killing of Streptococcus pneumoniae. Using the cathepsin D inhibitor pepstatin A, we demonstrate that cathepsin D differentially regulates multiple targets out of 679 proteins identified and quantified by eight-plex isobaric tag for relative and absolute quantitation. Our statistical analysis identified 18 differentially expressed proteins that passed all paired t-tests (α = 0.05). This dataset was enriched for proteins regulating the mitochondrial pathway of apoptosis or inhibiting competing death programs. Five proteins were selected for further analysis. Western blotting, followed by pharmacological inhibition or genetic manipulation of cathepsin D, verified cathepsin D-dependent regulation of these proteins, after exposure to S. pneumoniae. Superoxide dismutase-2 up-regulation was temporally related to increased reactive oxygen species generation. Gelsolin, a known regulator of mitochondrial outer membrane permeabilization, was down-regulated in association with cytochrome c release from mitochondria. Eukaryotic elongation factor (eEF2), a regulator of protein translation, was also down-regulated by cathepsin D. Using absence of the negative regulator of eEF2, eEF2 kinase, we confirm that eEF2 function is required to maintain expression of the anti-apoptotic protein Mcl-1, delaying macrophage apoptosis and confirm using a murine model that maintaining eEF2 function is associated with impaired macrophage apoptosis-associated killing of Streptococcus pneumoniae. These findings demonstrate that cathepsin D regulates multiple proteins controlling the mitochondrial pathway of macrophage apoptosis or competing death processes, facilitating intracellular bacterial killing
Modeling gas sorption in Amorphous Teflon through the Non Equilibrium Thermodynamics for Glassy Polymers (NET-GP) approach
No full textThe solubility of C2H6 and C2F6 in two amorphous glassy fluoropolymers, Teflon AF1600 and AF2400, has
been modeled with the non equilibrium statistical associating fluid (NE-SAFT) and non equilibrium perturbed hard sphere chain (NE-PHSC) theories. The study reveals
inadequate representation of the hydrocarbon solubility in fluoropolymers by the geometric mean rule used to
estimate the binary energetic interactions
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Effect of network structure modifications on the light gas transport properties of cross-linked poly(ethylene oxide) membranes
No full texttextCross-linked poly(ethylene oxide) (XLPEO) based on poly(ethylene glycol) diacrylate (PEGDA) is an amorphous rubbery material with potential applications for carbon dioxide removal from mixtures with light gases such as methane, hydrogen, oxygen and nitrogen. Changing the polymer network structure of XLPEO through copolymerization has previously been shown to influence gas transport properties, which correlated with fractional free volume according to the Cohen-Turnbull model. This project explores strategic modifications of the cross-linked polymer structure and their effect on the chemical, physical and gas transport properties with an aim to develop rational, molecular-based design rules for tailoring separation performance. Experimental results from calorimetric and dynamic thermal analysis studies are presented, along with pure gas permeability and solubility obtained at 35°C. Incorporation of dangling side chains by copolymerization of PEGDA with methoxy-terminated poly(ethylene glycol) methyl ether acrylate, n=8 (PEGMEA) was previously shown to be effective in increasing fractional free volume of XLPEO through the opening of local free volume elements, which in turn increased CO₂ permeability. Through a comparative study ofshort chain analogs to these co-monomers, incorporation of an ethoxy-terminated co-monomer was shown to be more effective than a comparable methoxy-terminated co-monomer in increasing gas permeability. For instance, copolymerization of PEGDA with 71 wt% ethoxy-terminated diethylene glycol ethyl ether acrylate increased CO₂ permeability from 110 barrer to 320 barrer. Gas permeability increase was not observed when hydroxy or phenoxy-terminated pendants were introduced, which was attributed to reduction in chain mobility due to increased inter-chain chemical interactions or steric restrictions, respectively. Based on these results, incorporation of a co-monomer containing a bulky non-polar terminal group, tris-(trimethylsiloxy)silyl, was examined in order to further increase gas permeability. Addition of 80 wt% TRIS-A co-monomer increased CO₂ permeability of cross-linked PEGDA to 800 barrer. However, the resulting changes in chemical character of the copolymer reduced CO₂/light gas selectivity, even as gas permeability increased. The effect of incorporating a bulky, stiff functional group in the cross-linker chain was studied using cross-linked bisphenol-A ethoxylate diacrylate, which showed 40% increase in permeability compared to cross-linked PEGDA. This study affirmed the importance of polymer chain interaction, in addition to free volume, in determining the gas transport properties of the polymer.Chemical Engineerin
An advanced decision process for capacity expansion in manufacturing networks
No full textManufacturing companies develop multiple production sites for various reasons from
cheaper labour to access to local markets. Expansion of capacity in such a
manufacturing network is a complex decision and requires consideration of multiple
factors. Traditionally, industrial decision makers attempt to minimise the cost of
expansion and, usually as an afterthought, consider soft factors like manpower
availability and logistics connectivity. This approach has gained acceptance as the
research community has focused on developing better mathematical representations of
the problem rather than investigate the larger decision process. A review of the
literature revealed that all existing processes for multi-site capacity expansion
decision fail in this way. Therefore, this research sets out to fulfil the needs of
practitioners by developing a more complete process for the capacity expansion
decision in multi-site manufacturing networks.
The research programme consists of five parts. In the first part an extensive literature
review is conducted to identify the state-of-the-art in capacity expansion decision
processes. Then, in the second part, a representative process is formed and industrially
tested. This generates the specifications for an advanced decision process which
addresses the shortcomings of the present body of knowledge and is developed in the
third part of the research. In the fourth part the advanced decision process is applied in
an industrial setting to validate its effectiveness. Finally, in the fifth part the advanced
decision process is refined and illustrated. The outcome of this research is an improved decision making capability. The
advanced decision process has been both validated and appreciated by industrial
practitioners. Specifically the contribution to knowledge is an advanced decision
process for capacity expansion in multi-site manufacturing network
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