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Prognostisering av framtida materialbehov i ERP-system : En fallstudie på Wexiödisk AB / Forecasting future material requirements in a ERP-system : A case study at Wexiodisk ABLönnblom, Oscar, Östergren, Viktor January 2023 (has links)
Utvecklingen av teknologin i dagens industrier förändras snabbt och för att bibehålla verksamhetens konkurrenskraft är det viktigt att förstå kundernas behov. Prognostisering är förväntat framtida behov baserad på historisk data. En prognos kan hjälpa ett företag med att planera och budgetera för framtida produktions- och distributions behov, samt fatta beslut om lagerhållning och inköp av råvaror. Syftet med studien är att undersöka framtida materialbehov med hjälp av prognostisering samt öka förståelsen samtidigt. Målet med studien är att få fram en metod för att utföra prognoser i ett affärssystem. De frågor studien kommer att besvara är “Hur kan användning av prognoser minska ledtider och bundet kapital?” & “Hur kan affärssystemet SAP användas för prognoser av en specifik produktgrupp?”Genom en förstudie om ämnet och därefter en fallstudie hos Wexiödisk kommer informationen att tas. Studien består av primära källor i form av intervjuer och sekundära källor i form av dokumentinsamling. Resultaten studien kom fram till var bland annat transaktionskoder och dess användningsområde, förklaring och utvärdering av parametrarna tillhörande materialplanering 1-4 och prognos. Dessutom hur en grundläggande prognos kan utföras med historiska värden. Resultatet redovisar även skillnaden i bundet kapital med hjälp av prognostisering.Den generella slutsatsen från studien är att med en parameterlösning och arbetssätt för att utföra prognosen besvaras frågan “Hur kan affärssystemet SAP användas för prognoser av en specifik produktgrupp?”. Vidare förslag om forskning och optimering kring parametrarna ges även för att få en mer exakt slutgiltig prognos. / The development of technology in today's industries is changing rapidly and in order to maintain the competitiveness of the business it is important to understand the needs of the customers. Forecasting is expected future demand based on historical data. A forecast can help a company plan and budget for future production and distribution needs, as well as make decisions about stocking and purchasing raw materials.The purpose of the study is to investigate future material needs using forecasting and to gaina greater understanding at the same time. The goal of the study is to come up with a method for performing forecasts in a business system. The questions the study will answer are "How can the use of forecasts reduce lead times and tied up capital?" & "How can the business system SAP be used for forecasts of a specific product group?"Through a preliminary study on the subject and then a case study at Wexiödisk, which the information will be taken from. The study consists of primary sources in the form of interviews and secondary sources in the form of document collection.The results of the study showed among other things, transaction codes and their area of use, explanation and evaluation of the parameters associated with MRP 1-4 and forecasting. Also, how a basic forecast can be performed using historical values. The result also reports the difference in tied up capital with the help of forecasting.The general conclusion of the study is that with a parameter solution and working method to perform the forecast, the question "How can the business system SAP be used for forecasts of a specific product group?" is answered. Further suggestions about research and optimization around the parameters are also given to get a more accurate final forecast.
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Les répercussions de l’insuffisance rénale chronique sur le transport des médicamentsNaud, Judith 05 1900 (has links)
L’insuffisance rénale chronique (IRC) affecte 13 % de la population américaine et son incidence ne cesse d’augmenter. Malgré un ajustement des doses de médicaments administrés en fonction du taux de filtration glomérulaire du patient urémique, près de 40 % des patients reçoivent une dose trop élevée en raison de modifications de l’élimination extrarénale des médicaments chez ces patients. Il est connu que l’IRC affecte l’élimination métabolique des médicaments par les cytochromes P450 et les enzymes de biotransformation de phase II. Nous avons aussi démontré, chez le rat, que l’IRC affecte l’expression et l’activité de transporteurs de médicaments intestinaux entraînant une augmentation de la biodisponibilité de certains médicaments. On retrouve des transporteurs de médicaments dans de nombreux organes comme le foie, les reins et la barrière hématoencéphalique (BHE) où ils jouent des rôles importants dans les éliminations biliaire et rénale et la pénétration des médicaments au cerveau.
Le but de ce travail était de mesurer, chez des rats néphrectomisés, les impacts de l’IRC sur l’expression protéique et génique et l’activité des transporteurs de médicaments hépatiques, rénaux et cérébraux. Les transporteurs étudiés sont de la famille des transporteurs ABC (P-glycoprotéine, multidrug-resistance related protein, breast cancer resistance protein) ou des solute carriers (organic anion transporter, organic anion transporting protein). Aussi, une étude réalisée chez l’humain visait à évaluer la pharmacocinétique de deux médicaments : la fexofénadine, un médicament majoritairement transporté, et le midazolam, un substrat du cytochrome P450 3A4, chez des sujets dialysés.
Nos résultats montrent que, chez le rat, l’IRC entraîne des modulations de l’expression des transporteurs d’influx et d’efflux hépatiques pouvant entraîner des diminutions du métabolisme hépatique et de l’excrétion biliaire des médicaments. Dans le rein, nous avons démontré des modulations de l’expression des transporteurs de médicaments. Nous avons aussi démontré que l’IRC diminue l’élimination urinaire de la rhodamine 123 et favorise l’accumulation intrarénale de médicaments transportés comme la benzylpénicilline et la digoxine. À la BHE, nous avons démontré des diminutions de l’expression des transporteurs de médicaments. Toutefois, nous n’avons pas observé d’accumulation intracérébrale de trois substrats utilisés (digoxine, doxorubicine et vérapamil) et même une diminution de l’accumulation intracérébrale de la benzylpénicilline. Il semble donc que, malgré les modulations de l’expression des différents transporteurs de médicaments, l’intégrité et la fonction de la BHE soient conservées en IRC.
Chez l’humain, nous avons démontré une augmentation de la surface sous la courbe de la fexofénadine chez les sujets dialysés, comparativement aux témoins, suggérant une altération des mécanismes de transport des médicaments chez ces patients. Nous n’avons, toutefois, pas observé de modification de la pharmacocinétique du midazolam chez les patients dialysés, suggérant une activité métabolique normale chez ces patients.
Un ou des facteurs s’accumulant dans le sérum des sujets urémiques semblent responsables des modulations de l’expression et de l’activité des transporteurs de médicaments observées chez le rat et l’humain. Ces travaux mettent en évidence une nouvelle problématique chez les sujets urémiques. Nous devons maintenant identifier les mécanismes impliqués afin d’éventuellement développer des stratégies pour prévenir la toxicité et la morbidité chez ces patients. / Chronic renal failure (CRF) affects 13% of the American population and its incidence is rising. Despite dose adjustment of drugs administered to CRF patients according to their glomerular filtration rate, nearly 40% of patients receive up to 6,45-times the recommended dose due to modifications in the extra-renal elimination of drugs. It is known that CRF affects the metabolic elimination of drugs via cytochrome P450s and Phase II biotransformation enzymes. Also, we showed modulations in the expression and activity of intestinal drug transporters in CRF rats that could lead to increases in the bioavailability of drugs. Drug transporters are expressed in various organs including the liver, the kidneys and the blood-brain barrier (BBB) where they play important roles in the biliary and renal elimination, and the brain penetration of drugs.
The objective of this work was to measure, using a rat model of CRF, the impacts of CRF on the protein and mRNA expression and the activity of liver, kidney and brain drug transporters. We studied ABC transporters (P-glycoprotein, multidrug-resistance related protein, breast cancer resistance protein) and solute carriers (organic anion transporters, organic anion transporting proteins). Also, a study conducted in human aimed to evaluate the pharmacokinetics of two drugs: fexofenadine, a transported drug, and midazolam, a substrate of cytochrome P450 3A4, in dialyzed patients.
In rats, our results show modulations in the expression and activity of hepatic influx and efflux drug transporters that could lead to decreases in the hepatic metabolism and biliary excretion of drugs. In the kidney, we demonstrated modulations in the expression of drug transporters in CRF rats. We also demonstrated that CRF causes a reduction of the urinary elimination of rhodamine 123, a P-glycoprotein substrate, and the intra-renal accumulation of at least two transported drugs: benzylpenicillin and digoxin. Finally, we demonstrated decreases in the expression of influx and efflux drug transporters at the BBB of CRF rats. However, these decreases did not correlate with in vivo changes since BBB permeability of benzylpenicillin was decreased in CRF rats while digoxin, doxorubicin and verapamil permeabilities were unchanged. It thus appears that, even with decreased drug transporters, BBB integrity and function is conserved in CRF.
In human, we showed an increase in the area under the curve of fexofenadine in dialyzed subjects compared to healthy controls, suggesting alterations of drug transport mechanisms in these patients. However, we observed no modifications in the pharmacokinetics of midazolam in dialyzed patients, suggesting a normal metabolic activity in these patients.
Results from in vitro studies suggest that one or many uremic factors accumulating in the serum of uremic rats and patients are responsible for the observed modulations in drug transporter expression and activity observed in rat and human. This work demonstrates the impacts of CRF on the expression and activity of drug transporters and how they could affect drug pharmacokinetics in patients. Now, the mechanisms leading to these modulations need to be identified in order to eventually develop strategies to prevent drug toxicity and morbidity in uremic patients.
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Logistika zvoleného podniku / Logistics of choosen plantMinaříková, Jana January 2011 (has links)
This thesis deals with material management.in CzechPak manufacturing plant. The main aim of the thesis is to analyse the current situation of logistics at CzechPak Manufacturing and propose changes to ease material management. Further aim is to point out key materials and suppliers. The thesis introduces the plant targets and postion of logistic targets within the plant strategy. In this thesis food industry features are specified with regards to logistic processes. The thesis gives proposals for process and system changes in material management with taking advantages of SAP system. In this thesis ABC analysis is applied on materials in CzechPak Manufacturing to indicate key materials and propose supplies optimization.
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Les répercussions de l’insuffisance rénale chronique sur le transport des médicamentsNaud, Judith 05 1900 (has links)
L’insuffisance rénale chronique (IRC) affecte 13 % de la population américaine et son incidence ne cesse d’augmenter. Malgré un ajustement des doses de médicaments administrés en fonction du taux de filtration glomérulaire du patient urémique, près de 40 % des patients reçoivent une dose trop élevée en raison de modifications de l’élimination extrarénale des médicaments chez ces patients. Il est connu que l’IRC affecte l’élimination métabolique des médicaments par les cytochromes P450 et les enzymes de biotransformation de phase II. Nous avons aussi démontré, chez le rat, que l’IRC affecte l’expression et l’activité de transporteurs de médicaments intestinaux entraînant une augmentation de la biodisponibilité de certains médicaments. On retrouve des transporteurs de médicaments dans de nombreux organes comme le foie, les reins et la barrière hématoencéphalique (BHE) où ils jouent des rôles importants dans les éliminations biliaire et rénale et la pénétration des médicaments au cerveau.
Le but de ce travail était de mesurer, chez des rats néphrectomisés, les impacts de l’IRC sur l’expression protéique et génique et l’activité des transporteurs de médicaments hépatiques, rénaux et cérébraux. Les transporteurs étudiés sont de la famille des transporteurs ABC (P-glycoprotéine, multidrug-resistance related protein, breast cancer resistance protein) ou des solute carriers (organic anion transporter, organic anion transporting protein). Aussi, une étude réalisée chez l’humain visait à évaluer la pharmacocinétique de deux médicaments : la fexofénadine, un médicament majoritairement transporté, et le midazolam, un substrat du cytochrome P450 3A4, chez des sujets dialysés.
Nos résultats montrent que, chez le rat, l’IRC entraîne des modulations de l’expression des transporteurs d’influx et d’efflux hépatiques pouvant entraîner des diminutions du métabolisme hépatique et de l’excrétion biliaire des médicaments. Dans le rein, nous avons démontré des modulations de l’expression des transporteurs de médicaments. Nous avons aussi démontré que l’IRC diminue l’élimination urinaire de la rhodamine 123 et favorise l’accumulation intrarénale de médicaments transportés comme la benzylpénicilline et la digoxine. À la BHE, nous avons démontré des diminutions de l’expression des transporteurs de médicaments. Toutefois, nous n’avons pas observé d’accumulation intracérébrale de trois substrats utilisés (digoxine, doxorubicine et vérapamil) et même une diminution de l’accumulation intracérébrale de la benzylpénicilline. Il semble donc que, malgré les modulations de l’expression des différents transporteurs de médicaments, l’intégrité et la fonction de la BHE soient conservées en IRC.
Chez l’humain, nous avons démontré une augmentation de la surface sous la courbe de la fexofénadine chez les sujets dialysés, comparativement aux témoins, suggérant une altération des mécanismes de transport des médicaments chez ces patients. Nous n’avons, toutefois, pas observé de modification de la pharmacocinétique du midazolam chez les patients dialysés, suggérant une activité métabolique normale chez ces patients.
Un ou des facteurs s’accumulant dans le sérum des sujets urémiques semblent responsables des modulations de l’expression et de l’activité des transporteurs de médicaments observées chez le rat et l’humain. Ces travaux mettent en évidence une nouvelle problématique chez les sujets urémiques. Nous devons maintenant identifier les mécanismes impliqués afin d’éventuellement développer des stratégies pour prévenir la toxicité et la morbidité chez ces patients. / Chronic renal failure (CRF) affects 13% of the American population and its incidence is rising. Despite dose adjustment of drugs administered to CRF patients according to their glomerular filtration rate, nearly 40% of patients receive up to 6,45-times the recommended dose due to modifications in the extra-renal elimination of drugs. It is known that CRF affects the metabolic elimination of drugs via cytochrome P450s and Phase II biotransformation enzymes. Also, we showed modulations in the expression and activity of intestinal drug transporters in CRF rats that could lead to increases in the bioavailability of drugs. Drug transporters are expressed in various organs including the liver, the kidneys and the blood-brain barrier (BBB) where they play important roles in the biliary and renal elimination, and the brain penetration of drugs.
The objective of this work was to measure, using a rat model of CRF, the impacts of CRF on the protein and mRNA expression and the activity of liver, kidney and brain drug transporters. We studied ABC transporters (P-glycoprotein, multidrug-resistance related protein, breast cancer resistance protein) and solute carriers (organic anion transporters, organic anion transporting proteins). Also, a study conducted in human aimed to evaluate the pharmacokinetics of two drugs: fexofenadine, a transported drug, and midazolam, a substrate of cytochrome P450 3A4, in dialyzed patients.
In rats, our results show modulations in the expression and activity of hepatic influx and efflux drug transporters that could lead to decreases in the hepatic metabolism and biliary excretion of drugs. In the kidney, we demonstrated modulations in the expression of drug transporters in CRF rats. We also demonstrated that CRF causes a reduction of the urinary elimination of rhodamine 123, a P-glycoprotein substrate, and the intra-renal accumulation of at least two transported drugs: benzylpenicillin and digoxin. Finally, we demonstrated decreases in the expression of influx and efflux drug transporters at the BBB of CRF rats. However, these decreases did not correlate with in vivo changes since BBB permeability of benzylpenicillin was decreased in CRF rats while digoxin, doxorubicin and verapamil permeabilities were unchanged. It thus appears that, even with decreased drug transporters, BBB integrity and function is conserved in CRF.
In human, we showed an increase in the area under the curve of fexofenadine in dialyzed subjects compared to healthy controls, suggesting alterations of drug transport mechanisms in these patients. However, we observed no modifications in the pharmacokinetics of midazolam in dialyzed patients, suggesting a normal metabolic activity in these patients.
Results from in vitro studies suggest that one or many uremic factors accumulating in the serum of uremic rats and patients are responsible for the observed modulations in drug transporter expression and activity observed in rat and human. This work demonstrates the impacts of CRF on the expression and activity of drug transporters and how they could affect drug pharmacokinetics in patients. Now, the mechanisms leading to these modulations need to be identified in order to eventually develop strategies to prevent drug toxicity and morbidity in uremic patients.
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Biological Roles of the Vitamin D Receptor in the Regulation of Transporters and Enzymes on Drug Disposition, Including Cytochrome P450 (CYP7A1) on Cholesterol MetabolismChow, Edwin C. Y. 15 August 2013 (has links)
Nuclear receptors play significant roles in the regulation of transporters and enzymes to balance the level of endogenous molecules and to protect the body from foreign molecules. The vitamin D receptor (VDR) and its natural ligand, 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], was shown to upregulate rat ileal apical sodium dependent bile acid transporter (Asbt) to increase the reclamation of bile acids, ligands of the farnesoid X receptor (FXR). FXR is considered to be an important, negative regulator of the cholesterol metabolizing enzyme, Cyp7a1, which metabolizes cholesterol to bile acids in the liver. In rats, decreased Cyp7a1 and increased P-glycoprotein/multidrug resistance protein 1 (P-gp/Mdr1) expressions pursuant to 1,25(OH)2D3 treatment was viewed as FXR effects in which hepatic VDR protein is poorly expressed. In contrast, changes in rat intestinal and renal transporters such as multidrug resistance associated proteins (Mrp2, Mrp3, and Mrp4), Asbt, and P-gp after administration of 1,25(OH)2D3 were attributed directly as VDR effects due to higher VDR levels expressed in these tissues. Higher VDR expressions were found among mouse hepatocytes compared to those in rats. Hence, fxr(-/-) and fxr(+/+) mouse models were used to discriminate between VDR vs. FXR effects in murine livers. Hepatic Cyp7a1 in mice was found to be upregulated with 1,25(OH)2D3 treatment, via the derepression of the short heterodimer partner (SHP). Putative VDREs, identified in mouse and human SHP promoters, were responsible for the inhibitory effect on SHP. The increase in hepatic Cyp7a1 expression and decreased plasma and liver cholesterol were observed in mice prefed with a Western diet. A strong correlation was found between tissue Cyp7a1 and P-gp changes and 1,25(OH)2D3 plasma and tissue concentrations, confirming that VDR plays an important role in the disposition of xenobiotics and cholesterol metabolism. Moreover, renal and brain Mdr1a/P-gp were found to be directly upregulated by the VDR in mice, and concomitantly, increased renal and brain secretion of digoxin, a P-gp substrate, in vivo. The important observations: the cholesterol lowering and increased brain P-gp efflux activity properties suggest that VDR is a therapeutic target for treatment of hypercholesterolemia and Alzheimer’s diseases, since beta amyloid, precursors of plague, are P-gp substrates.
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Biological Roles of the Vitamin D Receptor in the Regulation of Transporters and Enzymes on Drug Disposition, Including Cytochrome P450 (CYP7A1) on Cholesterol MetabolismChow, Edwin C. Y. 15 August 2013 (has links)
Nuclear receptors play significant roles in the regulation of transporters and enzymes to balance the level of endogenous molecules and to protect the body from foreign molecules. The vitamin D receptor (VDR) and its natural ligand, 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], was shown to upregulate rat ileal apical sodium dependent bile acid transporter (Asbt) to increase the reclamation of bile acids, ligands of the farnesoid X receptor (FXR). FXR is considered to be an important, negative regulator of the cholesterol metabolizing enzyme, Cyp7a1, which metabolizes cholesterol to bile acids in the liver. In rats, decreased Cyp7a1 and increased P-glycoprotein/multidrug resistance protein 1 (P-gp/Mdr1) expressions pursuant to 1,25(OH)2D3 treatment was viewed as FXR effects in which hepatic VDR protein is poorly expressed. In contrast, changes in rat intestinal and renal transporters such as multidrug resistance associated proteins (Mrp2, Mrp3, and Mrp4), Asbt, and P-gp after administration of 1,25(OH)2D3 were attributed directly as VDR effects due to higher VDR levels expressed in these tissues. Higher VDR expressions were found among mouse hepatocytes compared to those in rats. Hence, fxr(-/-) and fxr(+/+) mouse models were used to discriminate between VDR vs. FXR effects in murine livers. Hepatic Cyp7a1 in mice was found to be upregulated with 1,25(OH)2D3 treatment, via the derepression of the short heterodimer partner (SHP). Putative VDREs, identified in mouse and human SHP promoters, were responsible for the inhibitory effect on SHP. The increase in hepatic Cyp7a1 expression and decreased plasma and liver cholesterol were observed in mice prefed with a Western diet. A strong correlation was found between tissue Cyp7a1 and P-gp changes and 1,25(OH)2D3 plasma and tissue concentrations, confirming that VDR plays an important role in the disposition of xenobiotics and cholesterol metabolism. Moreover, renal and brain Mdr1a/P-gp were found to be directly upregulated by the VDR in mice, and concomitantly, increased renal and brain secretion of digoxin, a P-gp substrate, in vivo. The important observations: the cholesterol lowering and increased brain P-gp efflux activity properties suggest that VDR is a therapeutic target for treatment of hypercholesterolemia and Alzheimer’s diseases, since beta amyloid, precursors of plague, are P-gp substrates.
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Support consumers' rights in DRM : a secure and fair solution to digital license reselling over the InternetGaber, Tarek January 2012 (has links)
Consumers of digital contents are empowered with numerous technologies allowing them to produce perfect copies of these contents and distribute them around the world with little or no cost. To prevent illegal copying and distribution, a technology called Digital Rights Management (DRM) is developed. With this technology, consumers are allowed to access digital contents only if they have purchased the corresponding licenses from license issuers. The problem, however, is that those consumers are not allowed to resell their own licenses- a restriction that goes against the first-sale doctrine. Enabling a consumer to buy a digital license directly from another consumer and allowing the two consumers to fairly exchange the license for a payment are still an open issue in DRM research area. This thesis investigates existing security solutions for achieving digital license reselling and analyses their strengths and weaknesses. The thesis then proposes a novel Reselling Deal Signing (RDS) protocol to achieve fairness in a license reselling. The idea of the protocol is to integrate the features of the concurrent signature scheme with functionalities of a License Issuer (LI). The security properties of this protocol is informally analysed and then formally verified using ATL logic and the model checker MOCHA. To assess its performance, a prototype of the RDS protocol has been developed and a comparison with related protocols has been conducted. The thesis also introduces two novel digital tokens a Reselling Permission (RP) token and a Multiple Reselling Permission (MRP) token. The RP and MRP tokens are used to show whether a given license is single and multiple resalable, respectively. Moreover, the thesis proposes two novel methods supporting fair and secure digital license reselling. The first method is the Reselling Deal (RD) method which allows a license to be resold once. This method makes use of the existing distribution infrastructure, RP, License Revocation List (LRL), and three protocols: RDS protocol RD Activation (RDA) protocol, and RD Completion (RDC) protocol. The second method is a Multiple License Reselling (MLR) method enabling one license to be resold N times by N consumers. The thesis presents two variants of the MLR method: RRP-MR (Repeated RP-based Multi-Reselling) and HC-MR (Hash Chain-based Multi-Reselling). The RRP-MR method is designed such that a buyer can choose to either continue or stop a multi-reselling of a license. Like the RD method, the RRP-MR method makes use of RP, LI, LRL, and the RDS, RDA, and RDC protocols to achieve fair and secure reselling. The HC-MR method allows multiple resellings while keeping the overhead on LI at a minimum level and enable a buyer to check how many times a license can be further resold. To do so, the HC-MR utilises MRP and the hash chain cryptographic primitive along with LRL, LI and the RDS, RDA and RDC protocols. The analysis and the evaluation of these three methods have been conducted. While supporting the license reselling, the two methods are designed to prevent a reseller from (1) continuing using a resold license, (2) reselling a non-resalable license, and (3) reselling one license a unauthorised number of times. In addition, they enable content owners of resold contents to trace a buyer who has violated any of the usage rights of a license bought from a reseller. Moreover, the methods enable a buyer to verify whether a license he is about to buy is legitimate for re-sale. Furthermore, the two methods support market power where a reseller can maximise his profit and a buyer can minimise his cost in a reselling process. In comparison with related works, our solution does not make use of any trusted hardware device, thus it is more cost-effective, while satisfying the interests of both resellers and buyers, and protecting the content owner's rights.
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