efficiency optimization
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Basic research in cardiology ; Supplement Vol. 88. 2
XVI, 160 s. : tab., grafy ; 24 cm
- MeSH
- kardiovaskulární fyziologické jevy MeSH
- myokard MeSH
- srdce fyziologie MeSH
- Publikační typ
- kongresy MeSH
- sborníky MeSH
- Konspekt
- Lékařské vědy. Lékařství
- NLK Obory
- fyziologie
- etika, bioetika, lékařská etika
- kardiologie
- angiologie
Multienzyme processes represent an important area of biocatalysis. Their efficiency can be enhanced by optimization of the stoichiometry of the biocatalysts. Here we present a workflow for maximizing the efficiency of a three-enzyme system catalyzing a five-step chemical conversion. Kinetic models of pathways with wild-type or engineered enzymes were built, and the enzyme stoichiometry of each pathway was optimized. Mathematical modeling and one-pot multienzyme experiments provided detailed insights into pathway dynamics, enabled the selection of a suitable engineered enzyme, and afforded high efficiency while minimizing biocatalyst loadings. Optimizing the stoichiometry in a pathway with an engineered enzyme reduced the total biocatalyst load by an impressive 56 %. Our new workflow represents a broadly applicable strategy for optimizing multienzyme processes.
This article focuses on the problem of maximal compliance design of a hyper-elastic solid with the optimal design of human skin grafts as the application in mind. The solution method is a phasefield-based topology optimization method that supposes multiple local phasefields and a minimum distance constraint in order to prevent the phasefields from merging. Consequently, structurally disintegrating solutions such as by the coalescence of voids can be prevented. The method is used to find an optimal graft meshing pattern for a sample that is subjected to a biaxial extension of up to 150%, which corresponds to an expansion ratio of 1 : 2.25. Three prospective unitcell solutions that exhibit meta-material behavior are proposed for a periodic graft pattern. The results are a step toward improving the skin graft meshing efficiency. This work does not cover experimental validation.
- MeSH
- kůže * MeSH
- lidé MeSH
- prospektivní studie MeSH
- transplantace kůže * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In recent years, most countries around the world have struggled with the consequences of budget cuts in health expenditure, obliging them to utilize their resources efficiently. In this context, performance evaluation facilitates the decision-making process in improving the efficiency of the healthcare system. However, the performance evaluation of many sectors, including the healthcare systems, is, on the one hand, a challenging issue and on the other hand a useful tool for decision- making with the aim of optimizing the use of resources. This study proposes a new methodology comprising two well-known analytical approaches: (i) data envelopment analysis (DEA) to measure the efficiencies and (ii) data science to complement the DEA model in providing insightful recommendations for strategic decision making on productivity enhancement. The suggested method is a first attempt to combine two DEA extensions: flexible measure and cross-efficiency. We develop a pair of benevolent and aggressive scenarios aiming at evaluating cross-efficiency in the presence of flexible measures. Next, we perform data mining cluster analysis to create groups of homogeneous countries. Organizing the data in similar groups facilitates identifying a set of benchmarks that perform similarly in terms of operating conditions. Comparing the benchmark set with poorly performing countries we can obtain attainable goals for performance enhancement which will assist policymakers to strategically act upon it. A case study of healthcare systems in 120 countries is taken as an example to illustrate the potential application of our new method.
The main goal of this study is to demonstrate the possibility of training the Neural Network (multilayer perceptron) classifier and preprocessing units simultaneously, i.e., that properties of preprocessing are chosen automatically during the training phase. In the first realization step, adaptive recursive estimation of the power within a frequency band was used as a preprocessing unit. To improve the efficiency of special units, the power and momentary frequency estimation was replaced by methods that are based on adaptive Hilbert transformers. The strategy was developed to obtain optimized recognition units that can be efficiently integrated into strategies for monitoring the cerebral status of neonates. Therefore, applications (e.g., in neonatal EEG pattern recognition) will be shown. Additionally, a method of minimizing the error function was used, where this minimization is based on optimizing the network structure. The results of structure optimization in the field of EEG pattern recognition in epileptic patients can be demonstrated.
Mikročástice jsou předmětem intenzivního studia ve farmaceutické technologii. Důležitým parametrem při přípravě mikročástic je jejich enkapsulační účinnost. Vyšší hodnoty enkapsulační účinnosti vedou k zefektivnění výrobního procesu a následně k menší ekonomické zátěži. Cílem této studie byla příprava mikročástic metodou vnější gelace polosyntetického polymeru oxycelulosy s diklofenakem sodnou solí jako modelovým léčivem. Sledoval se vliv zvolených procesních proměnných na hodnotu enkapsulační účinnosti. Procesními proměnnými byly: teplota tvrdícího roztoku, přítomnost léčiva v tvrdícím roztoku a použití ultrazvukových vln při procesu vytvrzování. Jako optimální byla při přípravě mikročástic na bázi oxycelulosy vybrána metoda, při které se tvrdící roztok nasycený léčivem ochladil na teplotu 4 °C. Kombinace těchto parametrů vedla k nejvyšší enkapsulační účinnosti (šarže 4c – 75,24 %). Tvrzení mikročástic pomoci ultrazvukových vln se ukázalo jako nevhodné a mělo za následek snížení enkapsulační účinnosti.
Microparticles have been a subject of intensive studies in pharmaceutical technology, their encapsulation efficiency being an important parameter in the preparation of microparticles. Higher values of encapsulation efficiency result in a more effective manufacturing process and subsequently in lower economic costs. This study aimed to prepare microparticles with the use of the method of outer gelation of the semisynthetic polymer oxycellulose with diclofenac using sodium salt as the model agent and to examine the influence of selected processual variables on the value of encapsulation efficacy. Processual variables included: the temperature of the hardening solution, the presence of the active ingredient in the hardening solution and the use of ultrasound waves in the process of hardening. The method with the use of which the hardening solution saturated with the active ingredient was cooled to the temperature of 4 °C was selected as the optimal one for the preparation of microparticles on the base of oxycellulose. The combination of these parameters resulted in the highest encapsulation efficiency (batch 4c – 75.24%). Hardening of microparticles by means of ultrasound waves proved to be unsuitable and resulted in a decrease in encapsulation efficiency.
We introduce an easy but highly descriptive model of separation efficiency of dual-selector systems in capillary electrophoresis. The model expresses effective mobilities of analytes in dual-selector mixtures as a function of mixture composition and total concentration. The effective mobility follows the pattern familiar from single-selector systems, while complexation constant and mobility of the complex are replaced by the same but "overall" parameters and a total concentration of the mixture takes the role of a selector concentration. The overall parameters can be either calculated from the individual ones (an arbitrary mixture) or measured directly (a particular mixture). We inspected two model dual-selector systems consisting of heptakis(2,6-di-O-methyl)-β-CD and β-CD and of heptakis(2,6-di-O-methyl)-β-CD and 6-O-α-maltosyl-β-CD, and ibuprofen and flurbiprofen as model analytes (pH 8.2, non-enantioselective separation). Adopting any optimization strategy typically used in single-selector systems and finding an optimal mixture composition and total concentration is perhaps the prime benefit of the model. We demonstrate this approach on the selectivity parameter and show that the model is precise enough to be used in analytical practice. It also results that an electromigration order (reversal) of analytes can exhibit a rather curious dependency on the mixture composition and concentration. Last, the model can be used for better understanding of separation principles in dual-selector systems in general.
Současná efektivní antibiotická léčba vyžaduje moderní přístupy zaměřené na optimalizaci terapie a zpomalení růstu antimikrobiální rezistence. Klíčovým nástrojem v nemocnicích je koncept antimikrobiálního stewardshipu, který stojí na spolupráci v multidisciplinárních týmech složených z infektologů, mikrobiologů, klinických farmaceutů a epidemiologů. Tyto týmy se zaměřují na správnou volbu antibiotika a jeho dávkování, monitorování jeho účinnosti a minimalizaci nežádoucích účinků. Rozšiřující se možnosti v oblasti monitoringu a interpretace plazmatických koncentrací stále většího počtu antibiotik umožňují efektivně a bezpečně pracovat s dávkami a způsoby podání (prodloužené, kontinuální infuze) optimálními pro konkrétního pacienta, respektive umožňují personalizovaný přístup k farmakoterapii. Optimalizovat dávkování antibiotik pomáhá také využití moderních aplikačních pomůcek. V nemocničním prostředí ke zvýšení bezpečnosti vede rovněž elektronická parametrická ordinace, centralizovaná příprava a výdej antiinfektiv nemocniční lékárnou. V ambulantní sféře se rozšiřují možnosti prostřednictvím konceptu ambulantní parenterální antimikrobiální terapie, který snižuje riziko nozokomiálních infekcí a přináší komfort domácího prostředí pro pacienty. Jeho širšímu využití brání především nedostatečná oficiální stabilitní data antibiotických přípravků, ale i administrativní a finanční bariéry spojené se zaváděním tohoto inovativního konceptu do rutinní praxe.
The current effective antibiotic therapy requires modern approaches focused on optimizing treatment and slowing the growth of antimicrobial resistance. A key tool in hospitals is the concept of antimicrobial stewardship, which relies on collaboration in multidisciplinary teams composed of infectious disease specialists, microbiologists, clinical pharmacists, and epidemiologists. These teams focus on the correct choice of antibiotic and its dosage, monitoring its effectiveness and minimising adverse effects. Expanding possibilities in the field of monitoring and interpretation of plasma concentrations of an increasing number of antibiotics enable effective and safe optimization of dosing and administration methods (prolonged and continuous infusions) adjusted for individual patients, thereby allowing a personalized approach to pharmacotherapy. The optimization of antibiotic dosing is further supported using modern administration tools. In the hospital setting, electronic parametric prescribing, centralized preparation and dispensing of anti-infectives by the hospital pharmacy also leads to improved safety. In outpatient care, possibilities are expanding with the concept of outpatient parenteral antimicrobial therapy, which reduces the risk of nosocomial infections and provides the comfort of a home environment for patients. However, its broader use is hindered mainly by the lack of official stability data for antibiotic preparations, as well as administrative and financial barriers associated with integrating this innovative concept into routine practice.
In this paper we investigate the rate coding capabilities of neurons whose input signal are alterations of the base state of balanced inhibitory and excitatory synaptic currents. We consider different regimes of excitation-inhibition relationship and an established conductance-based leaky integrator model with adaptive threshold and parameter sets recreating biologically relevant spiking regimes. We find that given mean post-synaptic firing rate, counter-intuitively, increased ratio of inhibition to excitation generally leads to higher signal to noise ratio (SNR). On the other hand, the inhibitory input significantly reduces the dynamic coding range of the neuron. We quantify the joint effect of SNR and dynamic coding range by computing the metabolic efficiency-the maximal amount of information per one ATP molecule expended (in bits/ATP). Moreover, by calculating the metabolic efficiency we are able to predict the shapes of the post-synaptic firing rate histograms that may be tested on experimental data. Likewise, optimal stimulus input distributions are predicted, however, we show that the optimum can essentially be reached with a broad range of input distributions. Finally, we examine which parameters of the used neuronal model are the most important for the metabolically efficient information transfer.
- MeSH
- adenosintrifosfát metabolismus MeSH
- akční potenciály fyziologie MeSH
- excitační postsynaptické potenciály fyziologie MeSH
- membránové potenciály fyziologie MeSH
- modely neurologické * MeSH
- nervové vedení fyziologie MeSH
- nervový přenos fyziologie MeSH
- nervový útlum fyziologie MeSH
- neurony fyziologie MeSH
- počítačová simulace MeSH
- poměr signál - šum MeSH
- výpočetní biologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Recent COVID-19 vaccines unleashed the potential of mRNA-based therapeutics. A common bottleneck across mRNA-based therapeutic approaches is the rapid design of mRNA sequences that are translationally efficient, long-lived and non-immunogenic. Currently, an accessible software tool to aid in the design of such high-quality mRNA is lacking. Here, we present mRNAid, an open-source platform for therapeutic mRNA optimization, design and visualization that offers a variety of optimization strategies for sequence and structural features, allowing one to customize desired properties into their mRNA sequence. We experimentally demonstrate that transcripts optimized by mRNAid have characteristics comparable with commercially available sequences. To encompass additional aspects of mRNA design, we experimentally show that incorporation of certain uridine analogs and untranslated regions can further enhance stability, boost protein output and mitigate undesired immunogenicity effects. Finally, this study provides a roadmap for rational design of therapeutic mRNA transcripts.
- Publikační typ
- časopisecké články MeSH
