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Panacea: Predicting anti-aging combinations from expression analysisJatti, Ashwini January 2023 (has links)
Identifying interventions, such as drugs, that can counteract the effects of aging is crucial due to the complex nature of the aging process, which involves multiple biological processes. By targeting these processes, interventions have the potential to promote healthy aging. Utilizing pairs of drugs that exhibit synergistic effects becomes particularly effective as they can simultaneously impact multiple pathways associated with aging and reprogramming, enhancing their anti-aging potential. The Panacea (predicting anti-aging combinations from expression analysis) framework was developed to facilitate the discovery of such drug combinations. Deep generative models were incorporated into the Panacea framework to effectively capture complex patterns in gene expression data, leveraging their non-linear nature for an accurate representation of relationships and interactions. This makes them ideal for predicting drug combinations. The trained models, using the CMap dataset, demonstrated an improved performance to predict the effect of drugs. The age effect of these drug combinations was evaluated using an age-predictive model, revealing that synergistic anti-aging combinations mainly comprised reprogramming (the process of transforming one type of cell into another by altering its gene expression and properties), apoptosis (programmed cell death mechanism), and chemotherapy drugs, while pro-aging combinations involved cellular growth-limiting, longevity-extending, and chemotherapy drugs. These results emphasize the capability of deep generative models in predicting potent drug combinations for anti-aging and anti-cancer interventions.
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Structural evaluation of concrete buildings considering bearing capacity, load combinations, and safety regulations : Analyzing the difference design methods used in old Swedish Norms “Statliga betongbestämmelser 1949, BBK79, Eurocode” / Strukturell utvärdering av betongbyggnader med tanke på bärkapacitet, lastkombinationer och säkerhetsföreskrifter : Analysera skillnadsdesignmetoder som används i gamla svenska normer “Statliga betongbestämmelser 1949, BBK79, Eurocode”El-Sanei, Abdallah, Abdallah Mohammad, Najim January 2020 (has links)
Design regulations for concrete structures differ through time and place. Throughout the years design regulations have been changed and adjusted for improvement and to ensure safe and secured structures. In Sweden, several design codes and regulations were published from time to time, regulations that needed to be followed when designing structures for different purposes. Some of the design codes that were used during the 20th century were BABS (Byggnadsstyrelsens anvisningar till byggnadsstagdan, 1947-1968), SBN (Svensk Byggnom, 1968-1989), NR (Nybyggnadsregler, 1989-1994), and BKR (Boverkets Konstruktionsregler, 1994-2010) used for the consideration of load combinations on different structures. For design methods and theories “Statliga betongbestämmelser of year 1949” and “BBK 79, Nya betongbestämmelser” were published and used at that time. With development in the construction industry, new laws and regulations were issued to bear with today’s high standards and safety regulation. The Eurocodes were released to consider all new improvements and adjustments as well as facilitate trade between the European countries participating in the European standardization work, CEN. The Eurocodes were set as a base reference for several design purposes among the Europe area. The thesis was performed at the engineering consultancy company WSP to collect and assemble knowledge about the old norms and calculation methods and compare them with Eurocode and identify similarities and differences. The knowledge on the old and new codes was used to study two case studies. Case studies 1 and 2 are both office building structures where high and varying loads occur. Case study 1, built in 1954, consists of a 6-floor story building with the upper floors used as offices and the ground floor as commercial shops. Case study 2, built in 1961, consists of an 8-floor story building with 6 upper floors for office use and ground floors for commercial shops. From each case study one upper floor was chosen for the design and a continuous beam was designed for bending and shear. The design of columns was done on the last column which lays on the foundation of each building. The design calculations are made for beams and columns starting with “Statliga Betongsbestämmelser” as a reference code and the area of steel obtained from the dimensioning are kept the same in the design using “BBK79” and “Eurocode”. The variable difference are the load combinations that differ among the three codes BABS, SBN80 and Eurocode and the change in the design method which resulted in the change in the utilization ratio. The results were similar for both case studies which shows the consistency in the calculations. The total load q increased by 10% in SBN and 41% increase in Eurocode compared to BABS. This showed the change in safety standards by raising the total load on a structure by the use of partial coefficients. For beams in case 1, the utilization for bending was 98% of its capacity when designing using BABS with Statliga Betongsbestämmelser. This value decreased to 64% while using SBN80 with BBK79. In Eurocode the ratio of utilization increased to a value of 75%. Moreover, the utilization of columns in bending using BABS with Statliga betongbestämmelser showed a ratio of 84% and then decreased to 47% in SBN80 with BBK79 and increased somewhat to 51% in Eurocode. Regarding shear design all three norms were critical and strict in the method of design. It showed the importance and sensitivity of beams against shear. For BABS 67% of shear utilization was obtained and this value decreased to 54% in SBN and 52% in Eurocode. This shows the change in the method of designing using consecutive codes at three different times. The change concerns new concepts in the safety regulations from applying the safety on the material in the old norms to increasing the load and allow more usage of the material in the more recent codes. BBK79 and Eurocode share similarities in the design procedures and the use of the partial coefficient method. The increase of utilization in the Eurocode is due to the higher partial coefficient values and the modified load combination equations that resulted in a higher possible load than that from BBK79 but with almost the same load-bearing capacity in both BBK79 and Eurocode. / Genom åren har tillvägagångsättet för dimensionering av betongkonstruktioner reformerats. Äldre konstruktioner är beräknade med den norm som vid tidpunkten för projekteringen gällde. Variationer av normer som har använts under åren för lastkombinering är BABS (Byggnadsstyrelsens anvisningar till byggnadsstadgan 1947–1968), SBN (Svensk Byggnorm, 1968–1989), NR (Nybyggnadsregler, 1989– 1994) och BKR (Boverkets Konstruktionsregler, 1994–2010). Normer som använts för dimensionering är ”Statliga betongbestämmelser år 1949” och ”BBK 79, nya betongbestämmelser”. Eurokoder som är gemensamma dimensionsregler för bärverk i Europa började tillämpas dels för högre krav sattes på konstruktioner, dels för att underlätta handeln inom de länder som ingår i det europeiska standardiseringsarbetet CEN. Eurokoderna utgör en referensbas för olika ändamål vad gäller dimensionering av konstruktioner i Europa. Detta examensarbete genomfördes på med konsultföretaget WSP för att samla in och sammanställa kunskapen om gamla normer och beräkningsmetoder och jämföra dem med Eurokoderna och identifiera likheter och skillnader. Kunskapen om gamla och nya normer användes i två fallstudier. Fallstudierna 1 och 2 är båda kontorsbyggnader där höga och varierande laster förekommer. Fallstudie 1, byggt 1954, består av en sexvåningars byggnad med de övre våningarna för kontor och bottenvåningen för kommersiella affärslokaler. Fallstudie 2, byggd 1961, består av en åttavånings byggnad med de sex översta våningarna för kontor och de understa för affärslokaler. I varje fallstudie valdes ett övre våningsplan ut för dimensionering och en kontinuerlig balk dimensionerades för böjande moment och tvärkraft. Dimensioneringen av en pelare genomfördes för den sista pelarna som ansluter till respektive byggnads grundläggning. Konstruktionsberäkningarna görs för balkar och kolonner som börjar med ”Statliga Betongsbestämmelser” som en referenskod och armeringsarean från den dimensioneringen låses och används sedan vid dimensioneringen enligt ”BBK79” och “Eurocode”. Den variabla skillnaden är lastkombinationerna som skiljer sig mellan de tre koderna BABS, SBN80 och Eurokod och förändringen i dimensioneringsmetoden som resulterade i förändringen i utnyttjandegrad. Resultaten var liknande för båda fallstudierna som visar konsistensen i beräkningarna. Den totala belastningen q ökade med 10 % i SBN och 41 % ökning i Eurokod jämfört med BABS. Detta visade förändringen i säkerhetsstandarder genom att höja den totala belastningen på en struktur med hjälp av partiella koefficienter. För balken i fallstudie 1 var utnyttjandegraden för böjande moment 98 % av dess kapacitet vid dimensionering med BABS med Statliga Betongsbestämmelser. Detta värde minskade till 64 % när SBN80 och BBK79 användes. Med Eurokod ökade utnyttjandegraden till 75 %. Vidare visade dimensionering med BABS med Statliga betongbestämmelser en utnyttjandegrad för pelaren på 84 % som sedan minskade till 47 % med SBN80 och BBK79 och ökade något till 51 % med Eurokod. När det gäller tvärkraftsdimensionering var alla tre normer kritiska och strikta. Det visade vikten av och känsligheten hos balkar mot skjuvning. För BABS erhölls 67 % av kapaciteten för tvärkraft och detta värde minskade till 54 % i SBN och 52 % i Eurokod. Detta visar förändringen i metoden att dimensionera med hjälp av på varandra följande koder vid tre olika tidpunkter. Förändringen gäller nya koncept i säkerhetsföreskrifterna från att beakta säkerheten för materialet i de gamla normerna till att öka belastningen och möjliggöra en högre utnyttjandegrad av materialet i de nyare koderna. BBK79 och Eurocode delar likheter i konstruktionsförfarandena och användningen av metoden för partiell koefficient. Ökningen av utnyttjandet i Eurokoden beror på de högre partiella koefficientvärdena och de modifierade ekvationerna för belastningskombinationer som resulterade i en högre möjlig belastning än den från BBK79 men med nästan samma bärförmåga i både BBK79 och Eurokod.
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An Examination of the Inhibitory Effects of Antibiotic Combinations on Ribosome Biosynthesis in Staphylococcus aureusBeach, Justin 01 December 2013 (has links) (PDF)
Bacteremia initiated by Staphylococcus aureus infections can be a serious medical problem. Although a number of different antibiotics are used to combat staphylococcal infections, resistance has continued to develop. Combination therapy for certain infections has been used to reduce the emergence of resistance when a single agent has become ineffective. We hypothesize that the use of rifampicin and ciprofloxacin in combination with azithromycin, known for its inhibitory effects on the bacterial ribosome, can create potential synergistic effects resulting from indirect effects on ribosomal subunit synthesis.
To determine this we measured the effects of single and multiple antibiotics on cell growth rates, cell viability, and synthesis rates for DNA, RNA, and protein. We then measured synthesis rates of ribosomal subunits and the amounts of gyrase and RNAP. Effects of the antibiotic combinations on 70S ribosomes was assayed and the amounts of RNA and degradation was measured. We lastly studied the effects of these antibiotic combinations on mutation frequency in Staphylococcus aureus.
Our data have shown support not only for the use of antibiotic combination therapy but have provided strong evidence of an increase in the inhibition of bacterial ribosome assembly in Staphylococcus aureus. The reduction of 50S ribosomal subunit synthesis and 23S ribosomal RNA in cells grown in the presence of azithromycin, already known for it’s inhibitory effects on the 50S subunit synthesis, in combination with rifampicin or in combination with rifampicin and ciprofloxacin was observed. This also resulted in a reduction or elimination in the frequency of resistant cells when grown in the presence of these combinations.
These studies have shed light on the mechanism of action involved and synergistic effects occurring in combination antibiotic treatments and how ribosomal subunit assembly is affected. The insights gained through this research provide necessary information needed for the design of more potent antibiotic combinations. This will create a better understanding and new methods for eliminating the spread of harmful pathogens such as Staphylococcus aureus.
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Predicting threat capability in control systems to enhance cybersecurity risk determinationPrice, Peyton 01 May 2020 (has links)
Risk assessment is a critical aspect of all businesses, and leaders are tasked with limiting risk to the lowest reasonable level within their systems. Industrial Control Systems (ICS) operate in a different cybersecurity risk environment than business systems due to the possibility of second and third-order effects when an attack occurs. We present a process for predicting when an adversary gains the ability to attack an industrial control system. We assist leaders in understanding how attackers are targeting ICS by providing visualizations and percentages that can be applied to updating infrastructure or shifting personnel responsibilities to counter the threat. This new process seeks to integrate defenders and threat intelligence providers, allowing defenders to proactively defend their networks prior to devastating attacks. We apply the process by observing it under randomness with constraints and through a case study of the 2015 attack on the Ukrainian power grid. We find that this process answers the question of what an attacker can do, provides the ability for the defender to possess an updated understanding of the threat’s capability, and can both increase and decrease the probability that an attacker has a capability against a control system. This process will allow leaders to provide strategic vision to the businesses and systems that they manage.
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Cost Utility Analysis of Fixed Dose and Free Dose Combinations of Oral Medications in Type 2 Diabetes PatientsAnupindi, Vamshi Ruthwik 24 May 2016 (has links)
No description available.
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Increasing the Precision of Forest Area Estimates through Improved Sampling for Nearest Neighbor Satellite Image ClassificationBlinn, Christine Elizabeth 25 August 2005 (has links)
The impacts of training data sample size and sampling method on the accuracy of forest/nonforest classifications of three mosaicked Landsat ETM+ images with the nearest neighbor decision rule were explored. Large training data pools of single pixels were used in simulations to create samples with three sampling methods (random, stratified random, and systematic) and eight sample sizes (25, 50, 75, 100, 200, 300, 400, and 500). Two forest area estimation techniques were used to estimate the proportion of forest in each image and to calculate forest area precision estimates. Training data editing was explored to remove problem pixels from the training data pools. All possible band combinations of the six non-thermal ETM+ bands were evaluated for every sample draw. Comparisons were made between classification accuracies to determine if all six bands were needed. The utility of separability indices, minimum and average Euclidian distances, and cross-validation accuracies for the selection of band combinations, prediction of classification accuracies, and assessment of sample quality were determined.
Larger training data sample sizes produced classifications with higher average accuracies and lower variability. All three sampling methods had similar performance. Training data editing improved the average classification accuracies by a minimum of 5.45%, 5.31%, and 3.47%, respectively, for the three images. Band combinations with fewer than all six bands almost always produced the maximum classification accuracy for a single sample draw. The number of bands and combination of bands, which maximized classification accuracy, was dependent on the characteristics of the individual training data sample draw, the image, sample size, and, to a lesser extent, the sampling method. All three band selection measures were unable to select band combinations that produced higher accuracies on average than all six bands. Cross-validation accuracies with sample size 500 had high correlations with classification accuracies, and provided an indication of sample quality.
Collection of a high quality training data sample is key to the performance of the nearest neighbor classifier. Larger samples are necessary to guarantee classifier performance and the utility of cross-validation accuracies. Further research is needed to identify the characteristics of "good" training data samples. / Ph. D.
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Kvinnliga småföretagares vardag : ett livsformsperspektiv på balans mellan arbete och fritid / Everyday Life of Self Employed Women : Balance Between Time of Work and Leisure Time from a Life Mode PerspectiveSimonsson, Nina, Torpare, Åsa January 2007 (has links)
<p>SAMMANFATTNING</p><p>Vi lever i en tid av ständiga och snabba förändringar. Detta sägs även gälla i arbetslivet. Framförallt kvinnornas roll i arbetet är i förändring, de tar allt större plats inom företagsmarknaden. Det blir allt vanligare att kvinnor startar och driver företag, många av dessa är små.</p><p>Vårt gemensamma intresse för den realistiska livsformsanalysen och kvinnligt företagande blev grunden för detta arbete. Det var av intresse för oss att söka finna svar på hur kvinnliga småföretagare upplever sin situation gällande balans mellan fritid och arbete. Vi ville ta reda på vilka livsformer dessa kvinnor lever för att öka vår förståelse för hur detta påverkar synen på vad som är viktigt i livet och vilka medel de tar till för att nå sina mål i enlighet med detta.</p><p>Livsformsanalysen söker öka vår förståelse för andra individer och hur de väljer att leva sina liv. Alla har vi olika mål och medel för att nå dessa och olika definitioner på vad som är det goda livet. Den livsform vi lever styr på många sätt hur vi ser på verkligheten. Vi utgick från att ett livsformsperspektiv skulle vara fruktbart för denna undersökning då det skulle ge oss förklaringar till det som skiljer olika företagare åt. Vår förförståelse var att kvinnor till större del tar ansvar för hem och familj, det var därför spännande att utröna hur de klarar av att balansera detta ansvar med företagande.</p><p>Då det är upplevelsen av de kvinnliga småföretagarnas situation vi velat undersöka valde vi att göra en kvalitativ undersökning. Vi genomförde fem intervjuer med småföretagande kvinnor som visade sig leva olika livsformer och därmed ha olika förutsättningar för sitt företagande. Gemensamt för dem är att de alla delvis lever självständighetens livsform. I enlighet med detta har de svårt att skilja arbetsliv från privatliv. Analyser av materialet visade att den eller de livsformer företagaren lever påverkar hur hon söker finna balans i tillvaron.</p><p>Nyckelord: Livsformer, kombinationslivsform, balans, småföretagare och kvinnor</p> / <p>ABSTRACT</p><p>We are living in a time of constant and rapid change. This also applies to work life. This applies in particular on the women’s role at work, women gain more ground in the business market. It is becoming more common for women to start and lead their own businesses, many of these are small.</p><p>Our mutual interest in the realistic life mode analysis and in women who run their own businesses became the base of this composition. It was in our interest to find answers about how self employed women experience their situation concerning balance between leisure time and the time of work. We aspired to find out what life modes these women live. This in order to increase our understanding of how this influences their view of what is most important in life and the means they use to acquire their goals.</p><p>The life mode analysis was created to increase our understanding of other individuals and the way they chose to live their lives. All of us have different goals and means to reach them, we have also got different views of what the good life is. The life mode one person lives in many ways predicts how he or she looks upon reality. We assumed that a life mode perspective analysis would be productive on this study since it would explain the differences amongst the self employed women. Our pre understanding was that women usually take on the main responsibility for the home and family .It was interesting to us to find out how they manage to balance this responsibility and their businesses.</p><p>Since we wanted to explore the women’s experiences in our study we chose to make a qualitative research. We made five interviews with self employed women. We found out that they live different life modes, this gives them different conditions under witch they run their businesses. What they all have in common is that they, in part, live the independent life mode. In accordance to this they find it difficult to separate their time of work from their leisure time. Our analysis shows that the life mode or life modes influences how the business woman chooses to find her balance in life.</p><p>Key words: Life modes, combinations of life modes, balance, self employed women</p>
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Vývoj pravidel volejbalu a jeho vliv na rozvoj herních systémů a kombinací / Development of voleyball rules and its influence on the gameplay and combinationsKohlová, Zuzana January 2011 (has links)
TITLE: The development of voleyball rules and its influence on the gameplay and combinations ABSTRACT: The goal of my thesis is to study the influence of changes in volleyball rules on the developement of game systems and game combinations. In this paper I will attempt to answer and discuss the following scientific question: What influence have changes of the volleyball rules had on the developement of game systems and game combinations. I will chart the developement of volleyball rules from 1950 until present. I will study how the parametres of the playing field and its surroundings have changed. I will chart the developement of volleyball equipment, mainly the volleyball net and the ball. Based on studying the changes of volleyball rules, I will compare the developement of game systems and game combinations. I will compare the lengths of the games based on the changes of the rules. KEY WORDS: Volleyball, the rules of volleyball, game combinations in volleyball, game systems in volleyball.
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Analýza standardních situací ve futsalu FIFA / Analysis of standard situations in futsal FIFAHovorka, Miroslav January 2014 (has links)
Title: Analysis of standard situations in futsal FIFA Objectives: The main goal of this work is to observe solutions of standard situations by teams from the top futsal league. Another goal is to determine the effect of solving these situations onto the amount of goals scored and overall success. Methods: In this thesis were used methods of comparison, analysis and hypothesis testing. The method of comparison was used to compare the observed data with previous results of the bachelor thesis, which were also tested after that. The method of analysis was applied to the analysis of individual situations and standard solutions were then generalized by comparison with similar situations. Results: It was found that the standard conditions affect the game and their successful solutions cause a lot of goals for a team. Most goals are scored from direct free kicks and corner kicks. Most signals, game combinations, the teams practiced at corner kicks and sidekicks at the opponents half. Keywords: small form of football, game performance, game combination, solution of game tasks
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Nehmotná aktiva ve světově uznávaných účetních systémech / Intangible assets in world respected accounting systemsJirka, Jiří January 2009 (has links)
The diploma thesis focuses on intangible assets especially from IFRS point of view. Then principles of IFRS are compared with principles of US GAAP and Czech regulation. This thesis provides theoretical base which is explained on practical examples. Finally, the study on goodwill from business combinations and its impairment is carried out. Author evaluates its results and he is trying to clarify cause of high recorded goodwill.
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