Contextualist responses to the sceptic: conversational mechanisms for changing of the epistemic standards

Ovaj rad bavi se jednom od najaktuelnijih i najznačajnijih tema savremene epistemologije – kontekstualističkim rešenjem problema skepticizma. Konverzacioni kontekstualizam je epistemološko stanovište konstruisano radi objašnjenja mogućnosti ispravnog pripisivanja znanja saznajnim subjektima, uprkos radikalnim skeptičkim argumentima i hipotezama o sistematskoj obmani. Pored toga, konverzacioni kontekstualizam je istovremeno i pokušaj da se analizira i objasni veoma širok spektar različitih upotreba termina „znanje“ u svakodnevnom jeziku, s obzirom na različitost konverzacionih konteksta u kojima se taj termin koristi. Glavni predmet ovog rada jeste detaljna analiza problema koji se tiče mehanizama promene standarda za pripisivanje znanja, kao osnove za razjašnjenje kontekstualističkog odgovora skepticizmu. Posebna pažnja je usmerena na asimetriju koja se javlja između mehanizama za povišavanje i snižavanje standarda za pripisivanje znanja. Jedna od glavnih teza koju kontekstualisti zastupaju je da su mehanizmi povišavanja epistemičkih standarda ključni za objašnjenje načina na koji skeptički argumenti dobijaju na ubedljivosti i odakle crpe svoju snagu. Međutim, u objavljenim radovima na temu kontekstualizma, vrlo je malo reči o mehanizmima za snižavanje epistemičkih standarda u okviru konverzacionih konteksta. Jedna od glavnih tema kojima se rad bavi jeste upravo analiza mehanizama za snižavanje epistemičkih standarda kao ključnog koraka u pokušaju da se (svakodnevno) znanje sačuva od skeptičkih prigovora. U uvodnom poglavlju izlažu se osnovne postavke konverzacionog kontekstualizma. Razmatraju se najznačajnije razlike između kontekstualizma i nekih drugih tzv. varijantističkih pozicija, sa jedne strane, kao i klasičnih invarijantističkih teorija, sa druge strane. Takođe, izlaže se podela kontekstualističkih teorija s obzirom na nekoliko najznačajnijih kriterijuma. Najpre se analizira podela kontekstualističkih teorija s obzirom na kontekst u odnosu na koji se vrši procena istinitosnih vrednosti saznajnih tvrdnji, a zatim i u odnosu na mehanizam kojim se vrši promena standarda za pripisivanje znanja. U poslednjem odeljku autor eksplicira osnovnu ideju skepticizma, razmatrajući jedan od glavnih tipova skeptičkih argumenata. Drugo poglavlje bavi se problemom deduktivne zatvorenosti znanja. Princip prenošenja znanja putem implikacije predstavlja jedan od ključnih koraka u skeptičkoj argumentaciji, kojom se dovodi u pitanje naše svakodnevno znanje. Autor izlaže različita rešenja skeptičkog paradoksa, a zatim detaljno analizira podelu kontekstualističkih teorija s obzirom na odnos prema pomenutom principu. U zavisnosti od toga da li za osnovu uzimaju teoriju relevantnih alternativa ili teoriju protivčinjeničkih kondicionalnih iskaza, neke kontekstualističke teorije odbacuju princip deduktivne zatvorenosti znanja, dok ga druge prihvataju uz fiksiranost konverzacionog konteksta. Treće poglavlje je najznačajniji deo rada. U njemu se definišu epistemički standardi za pripisivanje znanja, a zatim se detaljno analiziraju mehanizmi za njihovo variranje. Autor razmatra nekoliko najznačajnijih kontekstualističkih pravila za povišavanje standarda za pripisivanje znanja, poput pravila pažnje, pravila osetljivosti i upadljivosti greške. Takođe, analizira se razlika između jednostavnog konverzacionog kontekstualizma i inferencijalnog kontekstualizma, s obzirom na različit pristup u objašnjenju mehanizama za variranje epistemičkih standarda. Poslednji odeljak ovog poglavlja bavi se detaljnom analizom mehanizama za snižavanje epistemičkih standarda i resetovanje konverzacionih konteksta, kao ključnog koraka u pokušaju da se svakodnevno znanje sačuva od skeptičkih scenarija. Autor razmatra mnoštvo različitih primera konverzacionih konteksta, stavljajući akcenat na analizu asimetrije koja se javlja između mehanizama za povišavanje i snižavanje epistemičkih standarda. Zaključno poglavlje predstavlja retrospektivu razmatranih problema koja prati osnovnu liniju argumentacije i izlaganja. Autor izlaže najznačajnije rezultate istraživanja, naročito onih koji se tiču mehanizama za promenu epistemičkih standarda. Posebna pažnja posvećuje se značaju objašnjenja mehanizama za snižavanje epistemičkih standarda i promenu konverzacionih konteksta, u nastojanju da se ponudi adekvatno rešenje problema skepticizma.The main focus of this thesis is one of the most topical and important themes of contemporary epistemology – contextualist solution to the problem of skepticism. Conversational contextualism is an epistemological viewpoint constructed towards explaining the possibility of legitimate knowledge ascriptions, despite the radical skeptical arguments and hypotheses of systematic deception. Conversational contextualism is also an attempt to analyze and explain the wide range of different meanings of the term „knows“ in ordinary language, considering many different conversational context in which that term is used. The principal goal of the thesis is a detailed analysis of the mechanisms for changing of the epistemic standards as a basis for the clarification of contextualist answers to the sceptic. Special interest is focused on the asymmetry between conversational mechanisms for increasing and decreasing of the epistemic standards. One of the main contextualist thesis is that the conversational mechanisms for increasing of epistemic standards are the key for explaining the means by which skeptical arguments get their legitimacy and draw their strength. However, in the most prominent papers on contextualism, there is very little attention towards conversational mechanism for the lowering of epistemic standards. One of the most important topics in this thesis is a detailed analysis of the conversational mechanisms for epistemic standards shifts, as a key step towards saving ordinary knowledge from skeptical arguments. In the opening chapter author discusses the main ideas of conversational contextualism. He explains the differences between contextualism and some classical invariantist theories and presents the main division of contextualist theories given couple of the most important criteria. First, he analyzes the distinction between contextualist theories based on the context relative to which the semantic evaluation of knowledge claims is considered, and then the distinction based on the way the epistemic standards are changed. In the last section author considers main ideas of skepticism by analyzing one of the most prominent skeptical arguments. The second chapter deals with the principle of deductive closure of knowledge. The entailment principle of knowledge is one of the most important steps in sceptic’s argumentation which he uses to question all of our ordinary knowledge. The author examines different solutions to the sceptic paradox and gives a detailed analysis of contextualist theories whether they accept or reject the principle of deductive closure of knowledge. By taking the relevant alternatives theory, or the theory of counterfactual conditionals, as their basis, some contextualist positions reject the closure principle, and some accept it with the fixation of conversational context. The third chapter represents the most important part of the thesis. In that chapter the author defines epistemic standards and then analyzes conversational mechanisms for their contextual shifts. He examines some of the most important conversational rules put up by leading contextualist philosophers, like the rule of attention, rule of sensitivity and the rule of salience. The author also indicates the most significant differences between simple conversational contextualism and inferential contextualism, according to the different approaches to the problem of contextual shifts. The last section of this chapter is dedicated to the most important question considering conversational mechanism for lowering of the epistemic standards, as a key step towards saving the ordinary knowledge from skeptical arguments. The author analyzes various different examples of conversational contexts, pinpointing the asymmetry between increasing and lowering of the epistemic standards. The last chapter is a retrospection of the considered problems, which follows the main line of argumentation and exposition. The author underlines the most significant results of the inquiry, especially those regarding conversational mechanisms for the change of epistemic standards. Special accent is put on the importance of an adequate explanation of conversational mechanisms for lowering of the epistemic standards, in an effort to propose successful resolution to the problem of skepticism

The analysis of 2,3-dicarboxypropane-1,1-diphosphonic acid-coated magnetite nanoparticles under an external magnetic field and their radiolabeling for possible theranostic applications

The advances in nanotechnology are directed towards the development of new theranostic agents based on magnetic nanoparticles that can be used for both cancer detection and treatment. In this study, 2,3-dicarboxypropane-1,1-diphosphonic acid-coated magnetite nanoparticles (Fe 3 O 4 -DPD MNPs) were evaluated for their theranostic application using different methods. The magnetic hyperthermia efficiency of the Fe 3 O 4 -DPD MNPs was investigated in saline solution with ionic strengths between 0.05 and 1.0 mol dm −3 . For a better understanding of hyperthermia, the behavior of Fe 3 O 4 -DPD MNPs under a non-alternating magnetic field was studied, and the transparency of the sample was measured. Furthermore, the radiotracer method using the radionuclides 99m Tc and 90 Y was applied as a reliable and powerful method for evaluating the in vivo behavior of a nanoprobe; a high radiolabeling yield (>93%), in vitro and in vivo stability of the radiolabeled nanoparticles and high heating effect were observed, thus paving the way for the possible theranostic applications of Fe 3 O 4 -DPD MNPs.This is the peer-reviewed version of the following article:Perić, M.; Radović, M.; Mirković, M. D.; Nikolić, A. S.; Iskrenović, P.; Janković, D.; Vranješ-Đurić, S. The Analysis of 2,3-Dicarboxypropane-1,1-Diphosphonic Acid-Coated Magnetite Nanoparticles under an External Magnetic Field and Their Radiolabeling for Possible Theranostic Applications. New Journal of Chemistry 2019, 43 (15), 5932–5939. [https://doi.org/10.1039/c8nj06478d]

DFT Analysis of Hyperfine Couplings in d and f metal complexes with Tetrahydro Borate Ligands

Metal complexes with BH4 - ligands show extravagant structural and dynamic properties, and possess many important and applicable qualities (potent reducing agents and catalysts, materials for hydrogen storage). Electron paramagnetic resonance (EPR) is very important for the characterization of complex compounds, determination of their electronic configuration and geometry. Also, Density Functional Theory (DFT) can predict EPR parameters and explain them more profoundly. Of particular importance is the analysis and prediction of hyperfine coupling constants for lanthanide complexes with BH4 - ligands, given that there is not much data in the literature. Within this paper hyperfine coupling constants of d and f metal complexes with BH4 - ligands have been determined by DFT calculations, and analyzed in detail. Calculations predicted that proton hyperfine coupling constants are very small in the case of complexes of f elements, and are present only due to weak polarization. The increase of covalence and the number of unpaired electrons does not significantly affect the change of constants of BH4 - ligands, but only of protons that are bound by σ bonds.XI Serbian Ceramic Society Conference - Advanced Ceramics and Application : new frontiers in multifunctional material science and processing : program and the book of abstracts; September 18-20, 2023; Belgrad

Estimation of measurement uncertainty in measuring radiopharmaceutical activity in dose calibrator

Doze kalibrator je jedan od osnovnih uređaja u nuklearnoj medicini, koji se koristi za merenje aktivnosti (doza) radiofarmaceutika koji se daju pacijentima bilo u dijagnostičke ili u terapijske svrhe. Aktivnosti gama i beta emitera različitih energija moraju da budu izmerene što tačnije da bi izlaganja ljudi (pacijenata) jonizujućem zračenju bila svedena na najmanji mogući nivo, a da se dobiju klinički značajni rezultati. Početna tačnost kalibratora (nesigurnost 5% ili manje) može se vremenom menjati kao rezultat promene pritiska u jonizacionoj komori ili električnog drifta. Zbog toga kontrola kvaliteta doze kalibratora treba da se sprovodi rutinski kako bi se osigurala tačnost i sledljivost merenja.U radu su prikazani rezultati procene nesigurnostipri merenjima aktivnosti radiofarmaceutika u doze kalibratoru u Laboratoriji za radioizotope. Komponente nesigurnosti, koje su važne za ova merenja, identifikuju se i uzimaju u obzir prilikom procene merne nesigurnosti. Razumevanje izvora nesigurnosti i korišćenje odgovarajućih korekcionih faktora mogu minimizirati netačna merenja.A dose calibrator is an essential device in a nuclear medicine, utilized for measurement the activity of radiopharmaceuticals administered to patients both for diagnostic and therapeutic purposes. It has to measurethe radioactivity of gamma and beta with different energies precisely for high quality imaging and for applying the right amount of radiation to treat disease. Initial accuracy (uncertainty 5% or less) may change with time as a result of changing pressureof the chamber gas and slow electrical drift. The quality controls should be undertaken on a routine basis to ensure the accuracy and traceability of measurements of the activities of radiopharmaceuticals.The paper presents the results of estimation of uncertainty in the measurement of the activity in the dose calibrator in the Laboratory for radioisotopes. The uncertainty components, that are important for these measurements, are identified and taken into account while estimating the uncertainty of measurement. Understanding the source of uncertainty and using appropriate techniques can minimize inaccurate measurements.Proceedings: [http://vinar.vin.bg.ac.rs/handle/123456789/8681]XXX симпозијум ДЗЗСЦГ (Друштва за заштиту од зрачења Србије и Црне Горе), 2- 4. октобар 2019. године, Дивчибаре, Србиј

Validation of an ITLC Method for the Determination of Radiochemical Impurities C in 99mTc-MIBI Injection

Prisustvo radiohemijske nečistoće C u 99mTc-MIBI injekciji utiče na kvalitet skena, jer se radiofarmaceutik nedovoljno nakuplja u organu od interesa, dok je aktivnost okolnih organa i tkiva velika. Zbog toga je i doza zračenja koju prime okolni organi i tkiva iznad propisanih granica. Da bi se obezbedilo da je planirano izlaganje zračenju pacijenata svedeno na minimum, farmakopeja zahteva ispitivanje sadržaja radiohemijske nečistoće C u 99mTc-MIBI injekciji neposredno pre primene radiofarmaceutika u pacijenta. Za ova ispitivanja se koriste metode hromatografije. U radu je predstavljena brza i osetljiva ITLC metoda namenjena za rutinsko ispitivanje sadržaja radiohemijske nečistoće C u 99mTc-MIBI injekciji. ITLC metoda je validirana, a ispitivani su pogodnost sistema, tačnost, preciznost, ponovljivost, specifičnost, limit detekcije, limit kvantifikacije, linearnost, robustnost i osetljivost metode. Dobre "recovery" vrednosti i niska relativna standardna devijacija potvrđuju da je predložena ITLC metoda pogodna za rutinsko određivanje nečistoće C u 99mTc-MIBI u injekciji.The European Pharmacopoeia mandates that all radiopharmaceuticals used in nuclear medicine for diagnostic and therapeutic purposes must be of the correct radiochemical and radionuclidic purity and have the correct radioactivity present at the stated time of injection to ensure that the intended radiation exposure of patients is kept to a minimum. These factors have an effect on the overall radiation dose to the patient, as impurities of the radionuclide and/or its chemical composition may affect the biodistribution of the injected radiopharmaceutical and consequently the radiation dose to any one particular organ or the whole body dose. The presence of radiochemical impurity C in 99mTc-MIBI injection affects the quality of the image, because 99mTc-MIBI accumulates insufficiently in the organ of interest, while the activity of the surrounding organs and tissues is high. Therefore, the radiation dose received by the surrounding organs and tissues is above the permitted level. In order to avoid unnecessary irradiation of surrounding organs and tissues, the pharmacopoeia requires examination of the content of radiochemical impurity C immediately before administering of 99mTc-MIBI to the patient. Chromatographic methods are used for these tests. The paper presents a fast and sensitive ITLC method intended for routine examination of the content of radiochemical impurity C in 99mTc-MIBI injection. The ITLC method was validated, and the suitability of the system, accuracy, precision, repeatability, specificity, limit of detection, limit of quantification, linearity, robustness and sensitivity of the method were examined. Good "recovery" values and low relative standard deviation confirm that the proposed ITLC method is suitable for routine determination of impurity C in 99mTc-MIBI in injection.XXXII Simpozijum Društva za zaštitu od zračenja Srbije i Crne Gore, 4-6. oktobar 2023; Budva, Crna GoraProceedings: [https://vinar.vin.bg.ac.rs/handle/123456789/11602

Method for Investigation of Physiological Distribution of 99mTc DPD

Radiofarmaceutici koji se koriste za ispitivanje skeletnog sistema od neprocenjivog su značaja u nuklearnoj medicini, kako za dijagnostiku primarnih tumora koštanog tkiva, tako i metastaza. Pre primene na pacijentima, ovi radiofarmaceutici podležu različitim fizičko-hemijskim i biološkim ispitivanjima. Ispitivanje fiziološke raspodele leka in vivo je od presudnog značaja jer od akumulacije leka u odgovarajućoj meri u ciljnom organu (skeletu) zavisi kvalitet dobijenog scintigrama, kao i doza zračenja koje će primiti pojedinačni organi i tkiva. U evropskoj farmakopeji (Ph.Eur.) date su metode kontrole kvaliteta kao i parametri kvaliteta sa granicama prihvatljivosti (specifikacijske granice) za 99mTc-metilendifosfonat (99mTc-MDP). Cilj ovog rada je prikaz metode ispitivanja fiziološke raspodele 99mTc-DPD koja je razvijena u Laboratoriji za radioizotope po smernicama evropske farmakopeje za 99mTc-MDP, uz manje modifikacije. Rezultati biodistribucije na Wistar pacovima su pokazali da je 99mTc-DPD proizveden u Laboratoriji za radioizotope zadovoljio sve postavljene kriterijume, kako odmah nakon proizvodnje, tako i nakon šest i dvanaest meseci od proizvodnje.Radiopharmaceuticals used to examine the skeletal system are of invaluable importance in nuclear medicine, both for the diagnosis of primary bone tissue tumors and metastases. Before administration to patients, these radiopharmaceuticals undergo various physico-chemical and biological tests. Investigation of the physiological distribution of the drug in vivo is of crucial importance because the quality of the obtained scintigram depends on the accumulation of the drug in the target organ (skeleton), as well as the radiation dose received by individual organs and tissues. The European pharmacopoeia (Ph.Eur.) provides quality control methods and quality parameters with acceptance limits (specification limits) for 99mTc-methylenediphosphonate (99mTc-MDP). The method of testing the physiological distribution of 99mTc-DPD in the Laboratory for Radioisotopes, which is presented in this paper, is done according to the guidelines of the European Pharmacopoeia for 99mTc-MDP, with minor modifications. Results of biodistribution on Wistar rats showed that 99mTc-DPD produced in the Laboratory for Radioisotopes met all the set criteria, both immediately after the production and after six and twelve months from production.XXXII Simpozijum Društva za zaštitu od zračenja Srbije i Crne Gore, 4-6. oktobar 2023; Budva, Crna GoraProceedings: [https://vinar.vin.bg.ac.rs/handle/123456789/11602

LABORATORY CNC MACHINE FOR EDUCATION OF STUDENTS IN CONTROL SYSTEMS ENGINEERING

Modern states seek to build a society based on knowledge, and in this sense, the IPA project ADRIA HUB aims to connect students, universities and companies into a single entity in which each party realizes many benefits. Practical part of this project consists of the pilot projects related to the improvements in the woodworking industry. For the purpose of the project realization, a specific laboratory CNC machine was designed and implemented by the Laboratory for Modeling, Simulation and Control Systems at the Faculty of Electronic Engineering in Niš. CNC machine, presented in this paper, is now actively used in laboratory work. Students have the opportunity to gain practical knowledge and master the techniques of controlling this machine as part of their studies in Control Systems Engineering

DATA DENOISING PROCEDURE FOR NEURAL NETWORK PERFORMANCE IMPROVEMENT

This paper will present training data denoising procedure for neural network performance improvement. Performance improvement will be measured by evaluation criterion which is based on a training estimation error and signal strength factor. Strength factor will be obtained by applying denoising method on a default training signal. The method is based on a noise removal procedure performed on the original signal in a manner which is defined by the proposed algorithm. Ten different processed signals are obtained from the performed method on a default noisy signal. Those signals are then used as a training data for the nonlinear autoregressive neural network learning phase. Empirical comparisons are made at the end, and they show that the proposed denoising procedure is an effective way to improve network performances when the training set possesses the significant noise component

Automation of the Production of Radiopharmaceutical with the Aim to Reduce the Operator's Radiation Dose

Laboratorija za radioizotope Instituta Vinča je jedinstven centar u regionu koji poseduje Rešenja Ministarstva zdravlja Republike Srbije i Direktorata za radijacionu i nuklearnu sigurnost i bezbednost Srbije za proizvodnju radiofarmaceutika. Radiofarmaceutik koji se proizvodi više od 40 godina u Laboratoriji za radioizotope, a primenjuje u terapiji tumora štitaste žlezde, kao i hipertireozi su kapsule natrijum-jodida (I-131). Radijacioni efekti I-131 na ćelije štitaste žlezde potiču od beta-zračenja koje emituje I-131 tokom radioaktivnog raspada u samoj štitastoj žlezdi jer se I-131 nakon oralne primene nakuplja prvenstveno u štitastoj žlezdi u kojoj ima dugu retenciju. Za efikasnu terapiju, ali u isto vreme u cilju smanjenja izloženosti nepotrebnim dozama, za svakog pacijenta određuje se odgovarajuća doza I-131 koju je neophodno da primi, odnosno primenjuje se tzv. personalizovana terapija. U radu je opisan postupak proizvodnje kapsula I-131 u Laboratoriji za radioizotope putem manuelnog punjenja kapsula rastvorom I-131, kao i osnovni zahtevi koje je neophodno da sistem za automatsku proizvodnju radiofarmaceutika ispuni, a to su pre svih, odgovarajuća zaštita operatera od zračenja, jednostavna upotreba i kompjuterska kontrola.The Laboratory for radioisotopes of the Vinča Institute is a unique center in the region with licences of the Ministry of Health of the Republic of Serbia and the Directorate for Radiation and Nuclear Safety and Security of Serbia for the production of radiopharmaceuticals. Sodium iodide (I-131) capsules are radiopharmaceuticals that have been produced for more than 40 years in the Laboratory for Radioisotopes, and are used in the treatment of tumors of thyroid gland, as well as in hyperthyroidism. The radiation effects of I-131 on thyroid cells originate from beta-radiation emitted by I-131 during radioactive decay in the thyroid gland itself because I-131 after oral administration accumulates primarily in the thyroid gland where it has a long retention. For the effective therapy, but at the same time in order to reduce exposure to unnecessary high doses, the appropriate dose of I-131 is determined for each patient, in the so-called personalized therapy. The paper describes the current procedure for the production of I-131 capsules in the Laboratory for Radioisotopes by manually filling the capsules with I-131 solution and the basic requirements for design the system for automating the production of radiopharmaceuticals, which above all must provide adequate protection for the operator from radiation, must be user friendly and computer-controlled.XXXII Simpozijum Društva za zaštitu od zračenja Srbije i Crne Gore, 4-6. oktobar 2023; Budva, Crna GoraProceedings: [https://vinar.vin.bg.ac.rs/handle/123456789/11602

Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT

Background: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5%-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of families with melanoma and whether performance improvements can be achieved. Methods: In total, 2116 familial melanoma cases were ascertained by the international GenoMEL Consortium. We recapitulated the MELPREDICT model within our data (GenoMELPREDICT) to assess performance improvements by adding phenotypic risk factors and history of pancreatic cancer. We report areas under the curve (AUC) with 95% confidence intervals (CIs) along with net reclassification indices (NRIs) as performance metrics. Results: MELPREDICT performed well (AUC 0.752, 95% CI 0.730-0.775), and GenoMELPREDICT performance was similar (AUC 0.748, 95% CI 0.726-0.771). Adding a reported history of pancreatic cancer yielded discriminatory improvement (P < .0001) in GenoMELPREDICT (AUC 0.772, 95% CI 0.750-0.793, NRI 0.40). Including phenotypic risk factors did not improve performance. Conclusion: The MELPREDICT model functioned well in a global data set of familial melanoma cases. Adding pancreatic cancer history improved model prediction. GenoMELPREDICT is a simple tool for predicting CDKN2A mutational status among melanoma patients from melanoma-prone families and can aid in directing these patients to receive genetic testing or cancer risk counseling