EASTERN EUROPE’S MELTING POT Bartoszewski, Jakub A.; Richter, Michael Martin
Journal of international affairs (New York),
09/2021, Letnik:
74, Številka:
1
Journal Article
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BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Substantial improvements have been made to cell culturing processes (e.g., higher product titer) in recent years by raising cell densities and optimizing cultivation time. However, this has been ...accompanied by an increase in product-related impurities and therefore greater challenges in subsequent clarification and capture operations. Considering the paradigm shift towards the design of continuously operating dedicated plants at smaller scales—with or without disposable technology—for treating smaller patient populations due to new indications or personalized medicine approaches, the rising need for new, innovative strategies for both clarification and capture technology becomes evident. Aqueous two-phase extraction (ATPE) is now considered to be a feasible unit operation, e.g., for the capture of monoclonal antibodies or recombinant proteins. However, most of the published work so far investigates the applicability of ATPE in antibody-manufacturing processes at the lab-scale and for the most part, only during the capture step. This work shows the integration of ATPE as a combined harvest and capture step into a downstream process. Additionally, a model is applied that allows early prediction of settler dimensions with high prediction accuracy. Finally, a reliable process development concept, which guides through the necessary steps, starting from the definition of the separation task to the final stages of integration and scale-up, is presented.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A comparison between engineered and commercially available l-lactate oxidases from Aerococcus viridans was conducted for biosensing applications. Enzymes were adsorbed onto the surfaces of graphite ...electrodes modified with multi-walled carbon nanotubes. Thermostable l-lactate oxidases were cloned with a (i) N-, (ii) a C-terminal His-tag and (iii) a wild-type enzyme. Subsequently to the heterologous expression in Escherichia coli and purification, we determined the kinetic parameters of these enzymes in solution. The kinetics of the wild-type, of the N-terminally His-tagged enzyme and of the commercial l-lactate oxidase from A. viridans were studied with a classical Michaelis–Menten as well as with a substrate inhibition model, while the enzyme carrying a C-terminal His-tag showed no activity. The active enzymes were used to fabricate and comparatively investigate multi-walled carbon nanotubes-based biosensors. The enzyme kinetic results were compared with electrochemical studies. By using both spectrophotometric and amperometric techniques, the inhibition phenomenon fits better to the data especially those data related with Lox-His-N. The electrochemical data of the fabricated enzymatic biosensors showed that the N-terminally His-tagged l-lactate oxidase performed best on carboxyl-modified carbon nanotubes. The sensor based on this engineered enzyme showed the highest sensitivity and lowest detection limit in the range of l-lactate concentration 0–1mM as well as long term stability over one month.
Low-density wood fiber insulation boards are traditionally manufactured in a wet process using a closed water circuit (process water). The water of these industrial processes contains natural ...phenolic extractives, aside from small amounts of admixtures (e.g., binders and paraffin). The suitability of two fungal laccases and one bacterial laccase was determined by biochemical characterization considering stability and substrate spectra. In a series of laboratory scale experiments, the selected commercial laccase from Myceliophtora thermophila was used to catalyze the surface modification of thermo-mechanical pulp (TMP) using process water. The laccase catalyzed the covalent binding of the phenolic compounds of the process water onto the wood fiber surface and led to change of the surface chemistry directly via crosslinking of lignin moieties. Although a complete substitution of the binder was not accomplished by laccase, the combined use of laccase and latex significantly improved the mechanical strength properties of wood fiber boards. The enzymatically-treated TMP showed better interactions with the synthetic binder, as shown by FTIR-analysis. Moreover, the enzyme is extensively stable in the process water and the approach requires no fresh water as well as no cost-intensive mediator. By applying a second-order polynomial model in combination with the genetic algorithm (GA), the required amount of laccase and synthetic latex could be optimized enabling the reduction of the binder by 40%.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Effort estimation by analogy uses information from former similar projects to predict the effort for a new project. Existing analogy-based methods are limited by their inability to handle ...non-quantitative data and missing values. The accuracy of predictions needs improvement as well. In this paper, we propose a new flexible method called AQUA that is able to overcome the limitations of former methods. AQUA combines ideas from two known analogy-based estimation techniques: case-based reasoning and collaborative filtering. The method is applicable to predict effort related to any object at the requirement, feature, or project levels. Which are the main contributions of AQUA when compared to other methods? First, AQUA supports non-quantitative data by defining similarity measures for different data types. Second, it is able to tolerate missing values. Third, the results from an explorative study in this paper shows that the prediction accuracy is sensitive to both the number N of analogies (similar objects) taken for adaptation and the threshold T for the degree of similarity, which is true especially for larger data sets. A fixed and small number of analogies, as assumed in existing analogy-based methods, may not produce the best accuracy of prediction. Fourth, a flexible mechanism based on learning of existing data is proposed for determining the appropriate values of N and T likely to offer the best accuracy of prediction. New criteria to measure the quality of prediction are proposed. AQUA was validated against two internal and one public domain data sets with non-quantitative attributes and missing values. The obtained results are encouraging. In addition, acomparative analysis with existing analogy-based estimation methods was conducted using three publicly available data sets that were used by these methods. Intwo of the three cases, AQUA outperformed all other methods.PUBLICATION ABSTRACT
At hydrothermal vent sites, chimneys consisting of sulfides, sulfates, and oxides are formed upon contact of reduced hydrothermal fluids with oxygenated seawater. The walls and surfaces of these ...chimneys are an important habitat for vent-associated microorganisms. We used community proteogenomics to investigate and compare the composition, metabolic potential and relative
protein abundance of microbial communities colonizing two actively venting hydrothermal chimneys from the Manus Basin back-arc spreading center (Papua New Guinea). We identified overlaps in the
functional profiles of both chimneys, despite differences in microbial community composition and venting regime. Carbon fixation on both chimneys seems to have been primarily mediated through the reverse tricarboxylic acid cycle and fueled by sulfur-oxidation, while the abundant metabolic potential for hydrogen oxidation and carbon fixation via the Calvin-Benson-Bassham cycle was hardly utilized. Notably, the highly diverse microbial community colonizing the analyzed black smoker chimney had a highly redundant metabolic potential. In contrast, the considerably less diverse community colonizing the diffusely venting chimney displayed a higher metabolic versatility. An increased diversity on the phylogenetic level is thus not directly linked to an increased metabolic diversity in microbial communities that colonize hydrothermal chimneys.
The canonical solution concept used in matching problems is pairwise stability, whose premise is that harmony is disrupted by any two agents intentionally leaving their partners to be with each ...other. We instead focus on scenarios in which harmony is disrupted merely by a single agent unilaterally initiating contact with a member of a different pair, whether or not his approach is reciprocated. A variety of solution concepts are proposed in which taboos, status, or power systematically limit such initiatives in order to achieve harmony.
Cytotoxic chemotherapy combinations and targeted agents represent established treatment concepts in advanced pancreatic neuroendocrine tumors (PNETs). However, response rates, side effects and ...outcome data strongly vary among these therapeutic approaches. Head-to-head comparisons between chemo- and molecular therapies are missing and secondary resistances frequently occur. The RamuNET trial aims to identify the effectiveness of dual treatment with DTIC and ramucirumab in progressive advanced PNET patients.
The RamuNET study is an investigator-initiated multicenter prospective single-arm trial to evaluate the efficacy of ramucirumab in combination with dacarbazine (DTIC) over a period of at least 6 months. Patients with progressive well-differentiated and metastatic pancreatic neuroendocrine tumors are eligible. The study aims to include 45 patients over a period of 24 months with a minimum follow-up of 24 months. The primary endpoint is disease control after 6 months. Secondary endpoints include progression-free survival, biochemical response, overall survival, quality of life and toxicity. Based on the hypothesis that 80% of the patients can achieve a disease control after 6 months, the sample size calculation follows an exact binomial single-stage design. H0: p < =p
= 60% versus H1: p > =p
= 80%, alpha = 0.05, beta = 0.1.
This study investigates a new therapeutic approach using the combination of cytotoxic and targeted antiangiogenic therapy in advanced PNET. If positive, this trial will be the basis for a randomized two-arm study to investigate the combination of ramucirumab and DTIC against other established therapies in PNET.
EudraCT: 2017-001207-68 . Date of registration: 2018.01.03.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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