Educational visualization of physical phenomena in the science park and school space

Tоком последњих деценија, значајан број физичара, астронома, географа, педагога, филозофа и архитеката истакли су потребу да се настава и учење физике и других природних наука одвијају у ширем простору, од учионице и лабораторије. Један сегмент овог рада указује на потребу да студенти добију прилику да понове искуства и резоновања научника, која су водила како до правилних, тако и она, која су водила до погрешних решења. У тези је истакнуто да су наставнику потребни ходник, двориште, кров, фасада, тераса да би се уградили уређаји и елементи који омогућују пресликавање, демонстрацију и проучавање физичких појава. Теза даје смернице и решења професорима и студентима како могу да реализују поменуте ситуације коришћењем ширег простора од учионице и лабораторије за физику. У истраживањима везаним за тему докторске дисертације проучаван је скуп конкретних спознајних инсталација погодних за ширење физичке лабораторије у комплекснији школски простор. Парк науке у Шапцу представља простор у којем је аутор тезе заједно са стручним тимом предложио, изградио, осмислио инсталације које су база едукационе визуелизације. Један сегмент тезе се бави усавршавањем оних учила која су раније већ предложена у литератури. Описан је и пут изградње инсталација и њиховог постављања у парку науке у Шапцу. Приказана је корисност Торичелијеве фонтане (која је изграђена у Шапцу) у учењу и примени у физици и математици и могућности примене квадратне функције и корена квадратне једначине. Њена употребљивост се заснива на визуелизацији математичких могућности облика индивидуалних водених млазева и групе млазева из суда напуњеног водом са бочним отворима. Рад сугерише да би наставници и аутори уџбеника требало да користе фонтану да би показали везу између физике и математике и да искористе ову везу у интегрисаном учењу две наведене науке. Један део рада је посвећен и грешкама у разматрању Торичелијеве фонтане у уџбеницима физике. Поред Торичелијеве фонтане анализиран је и Паралелни Глобус (Дан Ноћ и Година Глобус - ДИНГ). Овај Глобус је такође као саставни део докторског рада, осмишљен и исталиран у парку науке у Шапцу. ДИНГ је идеалан објекат за едукациону визуeлизацију знања о облику Земље, Земљиној ротацији око Сунца, дужини годишњих солстиција, еквиноција, локалног меридијана, дистрибуцију Сунчевог зрачења на Земљи, утицају овог зрачења на климу Земље, и како то зрачење користити ефикасно. ДИНГ је вишеструко користан за предавање физике, геофизике, астрономије и у развијању искуствено проблемског учења у подстицајној околини за ученика и јавност. У оквиру докторског рада изграђен је још један значајан број инсталација које едукационом визуелизацијом, пружају ученицима спознају о истраживачком путу научника и правилном резоновању кроз критичко мишљење. Са развојем информационо-комуникационих технологија едукациона визуелизација је постала посебна област научних истраживања са више нових праваца изучавања и развоја. У том контексту, теза истиче и анализира веома корисно повезивање визуелизације у реалном и виртуелном простору, а све у сврху наставе и учења. Такође, у раду и у складу са савременим тренутком описана је имплементација паметних телефона у посматрањима и мерењима како у физичкој лабораторији тако и у широј околини. У тези је такође урађено истраживање мисконцепције ученичких знања и промена њихових научних знања и ставова приликом рада у учионици на отвореном. Анализиран је едукативни утицај визуелно богате околине на наставу, успех, учење и популаризацију науке. На крају, представљена је тренутна позиција физике у образовању, стратегија развоја паркова науке и школских лабораторија на отвореном, као и мерљив утицај које могу направити у образовним програмима са циљем повећања интересовања ученика за бављење физиком и природним наукама.During last decades, considerable number of physicists, astronomers, geographers, pedagogues, psiholophers and architects have stressed the need that the physics and science teaching should be carried out in a broader space than the usual classrooms and labaratories. One segment of this work indicates the neceessity of providing students the opportunity to recreate experience and reasoning of scientists which led them to both, correct and incorrect solutions. In a thesis it is pointed out that a teacher needs a hall, a school yard, a roof, a facade, a terrace to install devices and elements for enabling mapping, demonstrations and studying physical phenomena. This thesis gives guidelines and keys to professors and students to realize mentioned situations by using broader space than a usual classroom and labratory for physics. In research related to the PhD reserach a group of concrete/authentic cognitive installations convinient for extending physics labaratory into more complex school space. Šabac Science Park is an example of space where the thesis author, with the expert team, suggested conteptualised installations based on educational visualization. One segment of thesis is devoted to advancing of teaching aids which were recommended earlier in the literature. The endeavour of the installations construction and its assembling in Šabac Science Park was described. The usefullness of Torriceli’s fountain in teaching applicability in physics of mathematical properties of the quadratic function and of the roots of the quadratic equation is demonstrated. The usefulness is based on the visualization of mathematical properties of the forms of individual water jets and of the sets of jets from the water tank with holes. Physics teachers and textbooks writers should use this fountain to show the interplay of physics and mathematics and to exploit this interplay in integrating physics and mathematics teaching and learning. Besides Torichelli`s fountain The Parallel Globe (Day Night Year Globe - DING) was built. Having the same orientiation in space as the Earth, DING shows in real time the pattern of illumination of the Earth’s surface and its diumal and seasonal variations. It is an ideal object for visualization of knowledge and rise of knowledge about the form of the Earth, Erath’s rotation around the Sun, the lenght of seasons solstices, equinoxes, the longitude problem, the distribution of Sun’s radiation over the Earth, the impact of these radiation on Earth’s climate, and how to use it efficiently. DING is simultaneously useful for teaching physics, geophysics, astronomy usage of solar energy and for experiencing inquiry learning environment by students and public. As a part of the PhD research, more than twenty installations were constructed. The installations provide to students the insight on research route of scientists and their correct reasoning through analytic thinking. Following the progress of communication technology, educational visusalisation has become a special field of scientific research branching into new ways of studies and development. Furthermore this work stresses and analyses very beneficial correlation of visualisation in real and virtual space aiming at efficient teaching and learning corresponding to actual trends to implement smartphones in observation and measuring in the physics laboratory as well as in the open space. The thesis also comprises the research of misconceptions in students’ knowledge and the change of their science knowledge and attitudes in classes in outdoors classrooms. Educational influence of visually enriched environment on teaching and learning progress, and popularisation of science has been analysed. Finally, current status of physics in educational system was presented. Strategy of developing science parks and outdoors school labaratories, and measurable impact they may have in curriculum aimed at motivating students to get more interested in styding physics and science in general, are present, as well

Investigation of clofazimine acid-base supersolubilization using various weak organic acids

Nowadays, more than two-thirds of potential drugs currently being discovered are practically insoluble in water with solubility <100 μg/mL. Despite that, compounds with even lower solubility (<0.1 μg/mL) are commonly selected for further development which is very challenging, especially in the pharmaceutical formulation process1. Clofazimine (CFZ), an anti-leprosy drug with inhibitory activity against several coronaviruses, has a favourable safety profile2, but it is poorly soluble in aqueous media. Hence, it is important to develop a method for increasing its solubility. In this work, a relatively novel approach of enhancing solubility of weakly basic drugs by using weak acids that would not form salts with the drug (acid-base supersolubilization (ABS)) has been applied. CFZ aqueous solubility was determined in solutions of tartaric, citric, malic, malonic or maleic acid: in set I acid solutions had the same concentration (2.5 mol/L), and in the set II they were scaled to the same pH (1.0). The drug was added in stirred acid solution until a precipitate was noticed and, after filtration, CFZ concentration in samples was determined by HPLC. Based on set I, it was found that the solubility of CFZ had the highest value in the case of tartaric acid (0.46 mg/mL) compared to other acid solutions of the same concentration. In set II the highest CFZ concentration was determined in the malic acid solution which had the highest concentration (2.8 mol/L) among other acids. On contrary, maleic acid solution at pH=1.0 had the lowest molar concentration (0.5 mol/L) and therefore CFZ was minimally dissolved. Further research will be directed toward the examination of acid structure effect on CFZ solubility

Gender Imbalance in the Number of PhD Physicists and in Key Decision-Making Positions in the Republic of Serbia

In Serbia, one of the former republics of Socialist Federal Republic of Yugoslavia, men and women have equal access to higher education and professional employment. However, in practice, this equality is not always realized. In this paper we describe the status of women in physics in Serbia, focusing on student gender ratios and on positions held. The financial contributions of the Serbian government to the scientific sector are not sufficient. Many young physicists enter the information technology sector, where they can earn higher salaries. In addition, the lack of career opportunities motivates scientists to go abroad, so each year, more and more young people leave Serbia. Today, many young Serbian physicists plan their departure during their studies and leave the country immediately after graduation. We present statis- tical data for the last several years, reviewing the percentage of women who are pursuing physics as a subject of study or a profession. We report gender ratios at various career stages. Teaching at the primary and high-school level is the main professional activity for female physicists in Serbia. Even though a large percentage (about 50%) of Serbian physicists are female, few women hold positions in which decisions about scientific and educational policy are made. When women achieve leadership positions, their educational attainments often outstrip those required for the positions. Only six women have a high-level management position

Drug solubility enhancement: from buffer complexes formation to acid-base supersolubilization

A majority of the new chemical entities (NCE) that emerged as potential drug candidates in pharmaceutical development during the past 2-3 decades are practically insoluble solids consisting of ionizable molecules [1]. Class II BCS drugs (Biopharmaceutics Classification System) exhibit poor bioavailability due to insufficient absorption in the gastrointestinal tract with slow drug release from the dosage forms and low solubility as the limiting steps for their absorption [2]. Thus, detailed and precise study of compound solubility and the possibilities to increase solubility and dissolution rate, are at the core of the development of bioavailable drug dosage forms and clinically effective pharmaceutical products that would dissolve in gastric and intestinal fluids after oral administration or not precipitate in the blood after intravenous administration. A white paper on consensus recommendations for improving data quality in equilibrium solubility measurement of ionizable drugs [3] emphasizes the importance of precise solubility measurements. As a part of solubility studies of a group of tricyclic antidepressants (TCAs) we have shown the influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and solid-phase transformations on the aqueous solubility of studied drugs [4-5]. A variety of methods to increase solubility and/or dissolution rate, and thereby increase their bioavailability, have been developed. Still, most of them, like particle size reduction, salt formation, conversion to amorphous form, solid dispersion, and solubilization in lipids or lipid-surfactant mixtures have their own limitations. To mitigate some of the above limitations, a novel method of drug solubilization in aqueous media by acid–base interactions has been developed [6]. This novel approach of greatly increasing the solubility is based on interactions of a model low-soluble basic drug in an aqueous medium with acidic species that would not normally form salts with it. Although quite successful, the proposed model still needs additional work and some fine-tuning with additional low-soluble drugs to establish it as a widely accepted method for increasing solubility, dissolution rate and bioavailability of poorly water-soluble drugs. Our research team is working on it

Clofazimine acid-base solubilization: influence of small organic acids’ concentration

Methods for drug solubilization have become important part of modern drug discovery and development due to increasing number of extremely insoluble drugs and drug candidates. One of such methods is acid-base supersolubilization (ABS) [1]. Clofazimine (CFZ) is weakly basic antibiotic and anti-inflammatory drug, most notably used in the treatment of leprosy and tuberculosis, with recently proven inhibitory activity against several coronaviruses [2]. We have recently unraveled its aqueous pKa value and its unique cosolvent dependence [3]. The aim of the present study was to investigate CFZ solubilization using the ABS approach. Eight small organic acids were tested for the ABS effect (glutaric, malic, tartaric, citric, malonic, maleic, succinic, adipic) but only glutaric (GA), malic (MA), and tartaric (TA) acids showed some solubilization effect. The effect of their concentration (and the solution pH value) was further tested. The solubility of CFZ was determined in GA, MA, and TA solutions in wide concentration (1.0×10-2 – 5.0 M) and pH range (~0.2 – 4.8). Equilibration time was 24 hours (6 h of stirring + 18 h of sedimentation). Phases were separated by filtration. The CFZ concentration in supernatant was determined by HPLC-UV/VIS. Results show that CFZ solubility increases as acid concentration increases: from 3.04×10-3 to 10.68 mg/mL (in GA), from 9.06×10-3 to 1.23 mg/mL (in MA) and from 4.76×10-3 to 0.32 mg/mL (in TA). The effect of CFZ solubilization is much more pronounced when the acid concentration is raised above 2 M. These results can be used as the basis for further CFZ formulation optimization. Furthermore, our ongoing research is focused on the type of interactions and other possible factors that can influence CFZ and other prectically insoluble drugs, embracing (super)solubilization as a general methodology in drug design and development

Clofazimine acid-base solubilization: influence of small organic acids’ concentration

Methods for drug solubilization have become important part of modern drug discovery and development due to increasing number of extremely insoluble drugs and drug candidates. One of such methods is acid-base supersolubilization (ABS) [1]. Clofazimine (CFZ) is weakly basic antibiotic and anti-inflammatory drug, most notably used in the treatment of leprosy and tuberculosis, with recently proven inhibitory activity against several coronaviruses [2]. We have recently unraveled its aqueous pKa value and its unique cosolvent dependence [3]. The aim of the present study was to investigate CFZ solubilization using the ABS approach. Eight small organic acids were tested for the ABS effect (glutaric, malic, tartaric, citric, malonic, maleic, succinic, adipic) but only glutaric (GA), malic (MA), and tartaric (TA) acids showed some solubilization effect. The effect of their concentration (and the solution pH value) was further tested. The solubility of CFZ was determined in GA, MA, and TA solutions in wide concentration (1.0×10-2 – 5.0 M) and pH range (~0.2 – 4.8). Equilibration time was 24 hours (6 h of stirring + 18 h of sedimentation). Phases were separated by filtration. The CFZ concentration in supernatant was determined by HPLC-UV/VIS. Results show that CFZ solubility increases as acid concentration increases: from 3.04×10-3 to 10.68 mg/mL (in GA), from 9.06×10-3 to 1.23 mg/mL (in MA) and from 4.76×10-3 to 0.32 mg/mL (in TA). The effect of CFZ solubilization is much more pronounced when the acid concentration is raised above 2 M. These results can be used as the basis for further CFZ formulation optimization. Furthermore, our ongoing research is focused on the type of interactions and other possible factors that can influence CFZ and other prectically insoluble drugs, embracing (super)solu bilization as a general methodology in drug design and development

The impact of educational reform and categorization of scientific journals and scientists on physics in Serbia

The trend of the increasing participation and importance of female physicists in Serbia continues. Many women have taken leading position in research and faculty governance and are contributing significantly to educational reform and the improvement of physics education in the primary and secondary schools

Revealing the story of an orphan drug: clofazimine speciation and solubilization as a function of pH

Since the introduction of combinatorial chemistry and high-throughput screening in drug discovery in the early 1990s, the solubility of new chemical entities (NCE) decreased drastically while their lipophilicities increased greatly. Characterizing physicochemical properties of low soluble molecules can be especially challenging, since such molecules can undergo complicated reactions in aqueous solution, such as forming precipitates or complexes with buffer species or undergoing self-aggregation (dimer, trimer, etc.)1,2 or micelle formations. Most drugs are ionizable. Foremost to the rational interpretation of solution behavior of ionizable drugs in a physiologically-relevant pH domain requires an accurate aqueous pKa, determined by a suitable method. In a pH-dependent measurement of a property (e.g. solubility-, lipophilicity-, permeability-pH), when the apparent pKa value is different from the true aqueous pKa value, it may be an early clue that nonideal solution behavior may be taking place. In pharmaceutical research, it may seem cost-effective to use calculated pKa instead of measured values, but paradoxically, such preference can lead to inaccurate rationalization of the pH-dependent behavior of the drug molecule. For simple molecules, calculated values can be useful, but for today’s new drugs or for molecules prone to complicated solution behavior, the use of calculated pKas can substantially wrench the interpretation of solution properties. Clofazimine (CFZ), although discovered about 66 years ago, and used therapeutically for nearly 40 years, exhibits some of the properties of relatively recent drug molecules by being extremely water insoluble and having variable pKa values reported. We have recently combined potentiometric titrations and UV/Vis spectrophotometry in methanol-water cosolvent media, accompanied by DFT calculations, to assess the hypothesis of CFZ free base dimerization. We reasoned that a soluble dimer might form from drug-drug adhesion along the hydrophobic molecular surface. With lessened exposure of the hydrophobic surface to water, the dimer would be more water soluble than the monomeric free base. In saturated solutions, the apparent solubility in alkaline pH would be elevated due to the presence of the dimer. The effect of that would be a lower pKa and reverse pKa cosolvent dependence – the behaviour we have noticed in CFZ aqueous solutions. These findings are of paramount importance for understanding of CFZ speciation and the future progress in developing its improved formulations which is the subject of our ongoing studies

Revealing the story of an orphan drug: clofazimine speciation and solubilization as a function of pH

Since the introduction of combinatorial chemistry and high-throughput screening in drug discovery in the early 1990s, the solubility of new chemical entities (NCE) decreased drastically while their lipophilicities increased greatly. Characterizing physicochemical properties of low soluble molecules can be especially challenging, since such molecules can undergo complicated reactions in aqueous solution, such as forming precipitates or complexes with buffer species or undergoing self-aggregation (dimer, trimer, etc.) or micelle formations. Most drugs are ionizable. Foremost to the rational interpretation of solution behavior of ionizable drugs in a physiologically-relevant pH domain requires an accurate aqueous pKa, determined by a suitable method. In a pH-dependent measurement of a property (e.g. solubility-, lipophilicity-, permeability-pH), when the apparent pKa value is different from the true aqueous pKa value, it may be an early clue that nonideal solution behavior may be taking place. In pharmaceutical research, it may seem cost-effective to use calculated pKa instead of measured values, but paradoxically, such preference can lead to inaccurate rationalization of the pH-dependent behavior of the drug molecule. For simple molecules, calculated values can be useful, but for today’s new drugs or for molecules prone to complicated solution behavior, the use of calculated pKas can substantially wrench the interpretation of solution properties. Clofazimine (CFZ), although discovered about 66 years ago, and used therapeutically for nearly 40 years, exhibits some of the properties of relatively recent drug molecules by being extremely water insoluble and having variable pKa values reported. We have recently combined potentiometric titrations and UV/Vis spectrophotometry in methanol-water cosolvent media, accompanied by DFT calculations, to assess the hypothesis of CFZ free base dimerization. We reasoned that a soluble dimer might form from drug-drug adhesion along the hydrophobic molecular surface. With lessened exposure of the hydrophobic surface to water, the dimer would be more water soluble than the monomeric free base. In saturated solutions, the apparent solubility in alkaline pH would be elevated due to the presence of the dimer. The effect of that would be a lower pKa and reverse pKa cosolvent dependence – the behaviour we have noticed in CFZ aqueous solutions. These findings are of paramount importance for understanding of CFZ speciation and the future progress in developing its improved formulations which is the subject of our ongoing studies