12 research outputs found

    Vloga družinskega zdravnika pri obravnavi bolnika s pljučnim rakom

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    Modeling water flow and phosphorus sorption in a soil amended with sewage sludge and olive pomace as compost or biochar

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    Organic amendments are often reported to improve soil properties, promote plant growth, and improve crop yield. This study aimed to investigate the effects of the biochar and compost produced from sewage sludge and olive pomace on soil hydraulic properties, water flow, and P transport (i.e., sorption) using numerical modeling (HYDRUS-1D) applied to two soil types (Terra Rosa and Rendzina). Evaporation and leaching experiments on soil cores and repacked soil columns were performed to determine the soil water retention, hydraulic conductivity, P leaching potential, and P sorption capacity of these mixtures. In the majority of treatments, the soil water retention showed a small increase compared to the control soil. A reliable fit with the modified van Genuchten model was found, which was also confirmed by water flow modeling of leaching experiments (R2 0.99). The results showed a high P sorption in all the treatments (Kd 21.24 to 53.68 cm3 g−1), and a high model reliability when the inverse modeling procedure was used (R2 0.93–0.99). Overall, adding sewage sludge or olive pomace as compost or biochar improved the Terra Rosa and Rendzina water retention and did not increase the P mobility in these soils, proving to be a sustainable source of carbon and P-rich materials

    Integrating animal tracking datasets at a continental scale for mapping Eurasian lynx habitat

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    Aim: The increasing availability of animal tracking datasets collected across many sites provides new opportunities to move beyond local assessments to enable de-tailed and consistent habitat mapping at biogeographical scales. However, integrating wildlife datasets across large areas and study sites is challenging, as species' varying responses to different environmental contexts must be reconciled. Here, we compare approaches for large-area habitat mapping and assess available habitat for a recolo-nizing large carnivore, the Eurasian lynx (Lynx lynx).Location: Europe.Methods: We use a continental-scale animal tracking database (450 individuals from 14 study sites) to systematically assess modelling approaches, comparing (1) global strategies that pool all data for training versus building local, site-specific models and combining them, (2) different approaches for incorporating regional variation in habi-tat selection and (3) different modelling algorithms, testing nonlinear mixed effects models as well as machine-learning algorithms.Results: Testing models on training sites and simulating model transfers, global and local modelling strategies achieved overall similar predictive performance. Model performance was the highest using flexible machine-learning algorithms and when incorporating variation in habitat selection as a function of environmental variation. Our best-performing model used a weighted combination of local, site-specific habi-tat models. Our habitat maps identified large areas of suitable, but currently unoccu-pied lynx habitat, with many of the most suitable unoccupied areas located in regions that could foster connectivity between currently isolated populations.Main Conclusions: We demonstrate that global and local modelling strategies can achieve robust habitat models at the continental scale and that considering regional variation in habitat selection improves broad-scale habitat mapping. More generally, we highlight the promise of large wildlife tracking databases for large-area habitat mapping. Our maps provide the first high-resolution, yet continental assessment of lynx habitat across Europe, providing a consistent basis for conservation planning for restoring the species within its former range.publishedVersio

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    Computational analysis of the MurC enzyme suitability for the design of new antibacterial agents

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    Bakterijska odpornost na trenutno dostopna antibiotična zdravila je eden največjih problemov javnega zdravja. K njenemu pojavu prispevata neustrezna in/ali prekomerna uporaba antibiotikov ter upadel razvoj novih antibiotičnih zdravil v zadnjih letih. Zato je razvoj novih protibakterijskih učinkovin nujen, pri čemer ga je smiselno usmeriti na mehanizme, ki so za obstoj bakterij nujni, kot sta na primer proces celične delitve ali biosinteza bakterijskega peptidoglikana. Eden izmed encimov, ki igrajo ključno vlogo pri biosintezi peptidoglikana, je encim UDP-N-acetilmuramat-L-alanin ligaza ali MurC. V okviru magistrske naloge smo zato s pomočjo različnih bioinformacijskih orodij, podatkovnih baz in programov poskušali ugotoviti, ali je encim MurC primerna tarča za razvoj novih protibakterijskih učinkovin. Pri analizi encima smo se osredotočili na ključne lastnosti potencialne tarče, kot so esencialnost gena, evolucijska ohranjenost aminokislin in sposobnost za vezavo učinkovine. Ugotovili smo, da je encim MurC esencialen za 43 bakterijskih organizmov, od katerih so trije organizmi ESKAPE. S pomočjo spletnega orodja UniProt smo ugotovili, da je izmed bakterij, pri katerih je znana sekvenca encima MurC, 11,7 % patogenih. S pomočjo analize evolucijske ohranjenosti aminokislin, poizvedb o napovedi potencialnih vezavnih mest in poizvedb o interakcijah aminokislin smo identificirali osem aminokislinskih položajev, ki so najprimernejši za tarčno ciljanje z učinkovino. Ti aminokislinski položaji encima MurC so: 128, 129, 130, 131, 173, 326, 346 in 352.Bacterial resistance to currently available antibiotic medicines is one of the most serious public health problems. The inadequate and/or excessive use of antibiotics and the decline in the development of new antibiotic drugs in recent years contribute to this phenomenon. For this reason, the development of new antibacterial agents is necessary, and it is useful to focus this development on the mechanisms necessary for the existence of bacteria, such as the process of cell division or the biosynthesis of bacterial peptidoglycan. One of the enzymes that play a key role in the biosynthesis of peptidoglycan is the enzyme UDP-N-acetylmuramate-L-alanine ligase or MurC. As part of our master\u27s thesis, we attempted to use various bioinformatics tools, databases and programmes to determine whether the MurC enzyme is a suitable target for the development of new antibacterial agents. In analysing the enzyme, we focused on key properties of the potential target, such as gene essentiality, evolutionary conservation of amino acids and druggability. We found that the MurC enzyme is essential for 43 bacterial organisms, three of which are ESKAPE organisms. Using the UniProt online tool, we found that of the bacteria for which the sequence of the MurC enzyme is known, 11.7% are pathogenic. Using amino acid evolutionary conservation analysis, queries to predict potential binding sites and queries on amino acid interactions, we identified 8 amino acid positions best suited for drug targeting. These amino acid positions of the MurC enzyme are: 128, 129, 130, 131, 173, 326, 346 and 352

    Use of ambiguous detections to improve estimates from species distribution models

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    International audienceAs large carnivores recover throughout Europe, there is a need to study their distribution to determine their conservation status and assess the potential for conflicts with human activities. However, efficient monitoring of many large carnivore species is challenging due to their rarity, elusive behavior and large home range size. In Europe, most current monitoring protocols rely on multiple detection methods, which can include opportunistic sightings from citizens in addition to designed surveys. Two types of detection errors may occur in such monitoring schemes; false negatives and false positives. When not accounted for, both can bias estimates from species distribution models (SDMs). False negative detections can be accounted for in SDMs that deal with imperfect detection. In contrast, false positive detections, due to species misidentification, have only rarely been accounted for in SDMs. Generally, researchers use ad hoc methods to avoid false positives through data filtering to discard ambiguous observations prior to analysis. These practices may discard valuable ecological information on the distribution of a species. Here, we investigated the costs and benefits of including data types that might include false positives rather than discard them for SDMs of large carnivores. We showcase a dynamic occupancy model that simultaneously accounts for false negatives and positives to jointly analyze data that include both unambiguous detections and ambiguous detections. Using simulations, we show that the addition of ambiguous detections increases the precision of parameter estimates. The analysis of data on the Eurasian lynx (Lynx lynx) suggested that incorporating ambiguous detections produced more precise estimates of the ecological parameters and revealed additional occupied sites in areas where the species is likely expanding. Overall, our work shows that ambiguous data should be considered when studying the distribution of large carnivores, through the use of dynamic occupancy models accounting for misidentification

    Gene therapy in oncology, first steps of development in Slovenia

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    Genska terapija postaja čedalje bolj zanimiva tudi v onkologiji. Med aplikacijami je morda najzanimivejša imunostimulacija. Pripravimo lahko plazmidno DNA, ki nosi zapis za različne imunostimulatorne molekule, ki jih vnesemo v celice tumorjev ali normalnih tkiv. Ta tkiva postanejo proizvajalci teh molekul, ki lahko delujejo lokalno ali pa se izločajo tudi sistemsko v krvni obtok. Ker plazmidna DNA ne prehaja celične membrane, so potrebni dostavni sistemi, virusni ali nevirusni. V naših študijah uporabljamo predvsem nevirusni dostavni sistem – elektroporacijo. Interlevkin 12 (IL-12) je eden od zanimivih citokinov, za katerega je znano protitumorsko delovanje s spodbujanjem imunskega odziva in antiangiogenim delovanjem. Namen projekta SmartGene.si je bil pripraviti plazmid z zapisom za interlevkin 12 (plazmid phIL12) in pripraviti vse potrebno za njegovo klinično testiranje za zdravljenje kožnih tumorjev. V konzorciju smo združili moči s partnerji z akademskega in industrijskega področja. Treba je bilo pripraviti plazmid za uporabo v humani onkologiji po zahtevah Evropske agencije za zdravila (EMA). Za prijavo klinične študije na Javno agencijo za zdravila in medicinske pripomočke (JAZMP) smo morali izvesti tudi vse neklinične raziskave o varnosti in učinkovitosti zdravila. Nato je bilo treba razviti postopek priprave zdravila, zagotoviti primerne prostore za pripravo in izvedbo postopka priprave zdravila. V treh letih smo dosegli vse te zastavljene cilje in dobili dovoljenje za izvajanje klinične študije na kožnih tumorjih, ki ga je izdala JAZMP na osnovi pozitivnega mnenja Komisije Republike Slovenije za medicinsko etiko. Zdaj poteka klinična študija faze I preizkušanja plazmida phIL12 na kožnih tumorjih glave in vratu z namenom preveriti varnost in sprejemljivost genskega elektroprenosa plazmida v tumorje. Cilj študije je prav tako določiti primeren odmerek zdravila, ki bi ga v nadaljnji klinični študiji uporabili kot adjuvantno zdravljenje k ablativnim terapijam, kot sta radioterapija ali elektrokemoterapija.Gene therapy is also attracting interest in oncology. Probably the most interesting approach is immunostimulation. Plasmid DNA can be constructed, which is coding for a specific immunostimulatory molecule, which is then delivered into the cells, either in tumour or normal tissue. The transfected tissue then becomes the producer of the molecules encoded in the plasmid. The product is then released from the cells, either locally or systemically into the bloodstream. Since plasmids have hampered transport through the plasma membrane, delivery systems are needed that are either viral or nonviral. In our studies we predominantly use the non-viral transfection system, based on electroporation of the cells. Interleukin 12 (IL-12) is a cytokine with well-known anti-tumour and anti-angiogenic function. Therefore, in the SmartGene.si project we wanted to construct a plasmid DNA which is coding for IL-12 (plasmid phIL12), and perform all the necessary testing and prepare the documentation for its clinical testing in the treatment of skin tumours. The SmartGene.si consortium comprises partners from academia and industry. In the project it was necessary to prepare the plasmid according to the European Medicinal Agency (EMA) recommendations. For the application for the study approval submitted to the Agency for Medical Products and Medical Devices of the Republic of Slovenia (JAZMP), it was necessary to perform pharmacological, pharmacokinetic, and efficiency testing of phIL12. Thereafter, we had to develop the process and the facility, and prepare the drug. During the last three years, we have achieved all the goals and obtained the approval of the JAZMP for clinical testing of the product phIL12 in humans. We also obtained the approval of the National Ethics Committee. Currently, we are testing phIL-12 in a Phase I clinical protocol on head and neck skin tumours, with the aim to test the safety and feasibility of intratumoral gene electrotransfer of the plasmid phIL12. Another goal of the study is to determine a suitable dose of plasmid that could be used in future studies as adjuvant treatment to ablative therapies such as radiotherapy or electrochemotherapy
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