Two-stage optimisation of the multiphase production

Two approaches to the optimisation of the multiphase production process are presented in this paper. The first model - model I is a static one, using enterprise input/output modelling and linear programming simultaneously. The second approach - model II is a dynamic one and represents the combination between discrete dynamic deterministic programming in the first stage and the model I in the second stage. An application from building industry is also presented in the paper

Overview of heuristics for the traveling salesman problem

Problem trgovskega potnika je iskanje najkrajše poti med vsemi mesti, kjer obiščemo vsako mesto natanko enkrat in se vrnemo nazaj na začetno mesto. Na problem lahko gledamo kot na iskanje najcenejšega cikla v grafu, ki obišče vse točke natanko enkrat. Pridobivanje optimalne rešitve problema trgovskega potnika je praktično neuporabno zaradi časovne zahtevnosti problema. Hevristični algoritmi so dobra alternativa optimalnemu reševanju problema, saj pridobijo rešitev v praktično izvedljivem času, a izgubijo jamstvo optimalne rešitve. Uvod diplomske naloge vsebuje osnovni opis problema trgovskega potnika. Temu sledijo primeri praktične uporabe problema, natančnejši opis problema, opredelitev hevristik in opis testnega okolja. Glavni del naloge vsebuje šest hevrističnih algoritmov, ki smo jih implementirali in jih testirali. Izbrali smo algoritem Lokalnega iskanja z operacijo k-opt, Lin-Kernighanov algoritem, algoritem Simuliranega ohlajanja, algoritem Kolonije mravelj, algoritem Optimizacije z roji delcev in algoritem Oponašanja volkov. Končni del naloge vsebuje primerjavo eksperimentalnih rezultatov in komentar nad uporabljeno metodologijo za primerjavo algoritmov.The Traveling Salesman Problem is finding the shortest path through all the cities, where each city is visited precisely once, while the first and the last city are the same. This can be formulated as searching for the shortest cycle in a graph which visits each vertex exactly once. Finding the optimal solution is practically fruitless due to the time complexity of the problem. Heuristic algorithms are good alternatives to algorithms, which search for the optimal solution, because a solution can be found in a practically achievable time framehowever, the guarantee of the solution being optimal is lost. The introduction of this work includes a basic description of The Traveling Salesman Problem, which is followed by a list of practical applications, a detailed description of the problem, the classification of heuristic algorithms and the details of the experimental environment. The main part of this work includes six algorithms, which were implemented and tested. The selected algorithms are Local Search with the k-opt operationLin-Kernighan algorithmSimulated AnnealingAnt Colony AlgorithmParticle Swarm Optimization and Wolfpack algorithm. The final part of this work is a comparison of the results from each algorithm and a commentary on the methodology that was used for the comparison of the algorithms

Cost-volume-profit analysis by using the enterprise input-output modeling

Enterprise input-output modeling (EIOM) can be used in a process of decision making for many purposes. In this paper the cost price models are developed to perform cost-volume-profit (CVP) analysis in a mass-production with the complex structure of a production process. An illustrative example trom the chemical industry is also presented, with the purpose to show the effect of a single factor or combination of factors (sales volume, level of activity, and selling/supply prices) on the financial results.Input-output models C-67; Optimization techniques C-61; Production, pricing and market structure - L 11

High Avidity Anti-β2-Glycoprotein i Antibodies Activate Human Coronary Artery Endothelial Cells and Trigger Peripheral Blood Mononuclear Cell Migration

Anti-β2-glycoprotein I antibodies (aβ2GPI) represent a potential pathogenic candidate for coronary artery diseases. High avidity aβ2GPI (HAv aβ2GPI) are known to be associated with thrombotic and obstetric manifestations in patients with antiphospholipid syndrome, who are also susceptible to the development of premature atherosclerosis. However, there is little information about how human coronary artery endothelial cells (HCAEC) are affected by HAv aβ2GPI. The purpose of our study was to evaluate the pathophysiological effects of HAv aβ2GPI on HCAEC and determine their influence on cytokine expression and migration of peripheral blood mononuclear cells. Following the two hit hypothesis, we co-stimulated HAv aβ2GPI-treated HCAEC in the presence and absence of the acute phase protein serum amyloid A (SAA). HAv aβ2GPI induced in vitro HCAEC dysfunction, through the ERK1/2 signaling pathway, promoted the expression of chemokines (MCP-1, GROα and IL-8) and IL-6, which led to the attraction and migration of peripheral blood mononuclear cells. These effects were potentiated and intensified in conditions with SAA, indicating that HAv aβ2GPI, in the presence of physiological concentrations of acute-phase proteins represent pathogenic autoantibodies, which could lead to the development of premature atherosclerosis and/or thrombosis development

Optimization of Unnicked β2-Glycoprotein I and High Avidity Anti-β2-Glycoprotein I Antibodies Isolation

Patient biological material for isolation of β2-glycoprotein I (β2GPI) and high avidity IgG anti-β2-glycoprotein I antibodies (HAv anti-β2GPI) dictates its full utilization. The aim of our study was to evaluate/improve procedures for isolation of unnicked β2GPI and HAv aβ2GPI to gain unmodified proteins in higher yields/purity. Isolation of β2GPI from plasma was a stepwise procedure combining nonspecific and specific methods. For isolation of polyclonal HAv aβ2GPI affinity chromatographies with immobilized protein G and human β2GPI were used. The unknown protein found during isolation was identified by liquid chromatography electrospray ionization mass spectrometry and the nonredundant National Center for Biotechnology Information database. The average mass of the isolated unnicked purified β2GPI increased from 6.56 mg to 9.94 mg. In the optimized isolation procedure the high molecular weight protein (proteoglycan 4) was successfully separated from β2GPI in the 1st peaks with size exclusion chromatography. The average efficiency of the isolation procedure for polyclonal HAv anti-β2GPI from different matrixes was 13.8%, as determined by our in-house anti-β2GPI ELISA. We modified the in-house isolation and purification procedures of unnicked β2GPI and HAv anti-β2GPI, improving the purity of antigen and antibodies as well as increasing the number of tests routinely performed with the in-house ELISA by ~50%

Atorvastatin in stable angina patients lowers CCL2 and ICAM1 expression: Pleiotropic evidence from plasma mRNA analyses.

Objective: Statin pleiotropy is still an evolving concept, and the lack of clarity on this subject is due at least in part to the lack of a definitive biomarker for statin pleiotropy. Using plasma mRNA analysis as a novel research tool for the non-invasive in vivo assessment of gene expression in vascular beds, we hypothesised that atorvastatin lowers the plasmamRNA level from statin pleiotropy-target genes, and the reduction is independent of the reduction of low-density lipoprotein cholesterol (LDL-C). Design and methods: Forty-four patients with stable angina received atorvastatin therapy (20 mg/day, 10 weeks). Plasma chemokine (C-C motif) ligand 2 (CCL2) and intercellular adhesion molecule-1 (ICAM1) mRNA levels and their protein concentrations (MCP-1, sICAM-1) were analysed before and after the treatment. Plasma vascular adhesion molecule-1 (sVCAM-1) concentrations were also analysed. Results: Atorvastatin lowered plasma mRNA levels (CCL2: −31.76%, p = 0.037; ICAM1: −34.09%, p b 0.001) and MCP-1 protein concentration (−18.88%, p = 0.008) but did not lower sICAM-1 and sVCAM-1 protein concentrations, and the decreases appeared to be independent from the lowering of LDL-C. The plasma mRNA levels correlated with their protein concentrations following statin treatment only. Conclusion: Our results significantly strengthen the clinical evidence in support of statin pleiotropy. Furthermore, this unique simultaneous measurement of plasma mRNAs and their protein concentrations offers an advanced non-invasive in vivo assessment of the circulation patholog

Investigation of drug product and container-closure interactions: A case study of diluent containing prefilled syringe.

Prefilled syringes (PFS) constitute a widely used medical device for drug delivery particularly for the drugs of biological origin. Interactions between the product contents and the components of the PFS play a critical role in determining the suitability of selected PFS. A diluent (with benzyl alcohol/BzOH as a preservative) containing PFS used for reconstitution of the lyophilized product revealed a systematic decrease in the BzOH content during accelerated and stress stability program. Investigation was carried out to understand and identify the underlying causes of this phenomenon. BzOH has a varying propensity to bind to the rubber components (stopper and tip-cap) of the PFS. Vapor permeation behavior across the tip-cap of the PFS was studied via headspace-gas chromatography-mass spectroscopy (HS-GC-MS) enabled analysis. Depending on the properties of the rubber components, BzOH can not only bind but also traverse across them, resulting in a systematic loss during the course of the stability. PFS can allow not only water vapor permeation across the tip-cap as shown in previous studies, but also molecules like benzyl alcohol. This phenomenon stresses the need for careful selection of the components of the primary packaging and also provides an opportunity to deploy novel tools like HS-GC-MS in the early selection of the optimal primary packaging configuration