Methodological framework for shrinking cities case study research: northwest region of Bosnia and Herzegovina

Urban shrinkage is an increasingly global phenomenon that equally affects large cities and small towns, as a result of complex social, economic and spatial changes, thereby causing the emergence of the so-called shrinking cities. This paper presents a model for the analysis of shrinking cities tailored to the needs of research in circumstances of insufficiently developed statistical systems for monitoring the complex structure of changes affecting cities. The model is based on an analysis of international research projects focused on this research problem, analysis of the legislative framework in Bosnia and Herzegovina (B&H) and analysis of available data. The proposed model is tested on the territory of northwest B&H (Republic of Srpska - RS) and aims at mapping, analysis and typological classification of shrinking cities. It is assumed that the process of urban shrinkage is more prevalent than that of urban growth, and that most of the cities and towns in northwest B&H (RS) are faced with this problem, which is considerably more acute when it comes to small and medium-sized towns of this region

A systematic review of protocol studies on conceptual design cognition: design as search and exploration

This paper reports findings from the first systematic review of protocol studies focusing specifically on conceptual design cognition, aiming to answer the following research question: What is our current understanding of the cognitive processes involved in conceptual design tasks carried out by individual designers? We reviewed 47 studies on architectural design, engineering design and product design engineering. This paper reports 24 cognitive processes investigated in a subset of 33 studies aligning with two viewpoints on the nature of designing: (V1) design as search (10 processes, 41.7%); and (V2) design as exploration (14 processes, 58.3%). Studies on search focused on solution search and problem structuring, involving: long-term memory retrieval; working memory; operators and reasoning processes. Studies on exploration investigated: co-evolutionary design; visual reasoning; cognitive actions; and unexpected discovery and situated requirements invention. Overall, considerable conceptual and terminological differences were observed among the studies. Nonetheless, a common focus on memory, semantic, associative, visual perceptual and mental imagery processes was observed to an extent. We suggest three challenges for future research to advance the field: (i) developing general models/theories; (ii) testing protocol study findings using objective methods conducive to larger samples and (iii) developing a shared ontology of cognitive processes in design

Can Galactic Cosmic Rays Account for Solar 6Li Without Overproducing Gamma Rays?

Cosmic-ray interactions with interstellar gas produces both 6Li, which accumulates in the interstellar medium (ISM), and $\pi^0$ mesons, which decay to gamma-rays which propagate throughout the cosmos. Local 6Li abundances and extragalactic gamma-rays thus have a common origin which tightly links them. We exploit this connection to use gamma-ray observations to infer the contribution to 6Li nucleosynthesis by standard Galactic cosmic-ray (GCR) interactions with the ISM. Our calculation uses a carefully propagated cosmic-ray spectrum and accounts for 6Li production from both fusion reactions ($\alpha \alpha \to ^6Li$) as well as from spallation channels ({p,\alpha+CNO \to ^6Li). We find that although extreme assumptions yield a consistent picture, more realistic ones indicate that solar 6Li cannot be produced by standard GCRs alone without overproducing the hadronic gamma rays. Implications for the primordial 6Li production by decaying dark matter and cosmic rays from cosmological structure formation are discussed. Upcoming gamma-ray observations by GLAST will be crucial for determining the resolution of this problem.Comment: 4 pages, 1 figure To be published in ApJ

Urban shrinkage in a 'shrinking' serbia - the approach to a global phenomenon in a local context

The initial purpose of this research was to understand the basic patterns of urban shrinkage in Serbia. Urban shrinkage, a common phenomenon in post-socialist countries, is a novelty, albeit very present in Serbia today. Despite presenting a huge challenge for the future of the country, it has not been studied sufficiently at any level. To understand this situation, the first "task" would certainly be to identify which cities in Serbia can be considered as shrinking in a local context. The research will focus on this issue through the development of four models of shrinking cities in Serbia according to globally based factors of urban shrinkage. The aim of the paper is to clarify the potential of their use and to explore the possible locally-based factors of urban shrinkage

Understanding the diffuse gamma ray emission of the milky way - from supernova remnants to dark matter

Diffuse gamma ray emission from the Galactic center at 2-3 GeV, as well as the 12 TeV gamma ray excess in the Galactic disk, remain open for debate and represent the missing puzzles in the complete picture of the high-energy Milky Way sky. Our papers emphasize the importance of understanding all of the populations that contribute to the diffuse gamma background in order to discriminate between the astrophysical sources such as supernova remnants and pulsars, and something that is expected to be seen in gamma rays and is much more exotic - dark matter. We analyze two separate data sets that have been measured in different energy ranges from the ?Fermi-LAT? and ?Milagro? telescopes, using these as a powerful tool to limit and test our analytical source population models. We model supernova remnants and pulsars, estimating the number of still undetected ones that contribute to the diffuse background, trying to explain both the Galactic center and the 12 TeV excess. Furthermore, we aim to predict the number of soon to be detected sources with new telescopes, such as the ?HAWC?

Antigenotoxic effects of royal jelly in the sex linked recessive lethal test with Drosophila melanogaster

The antitoxic and antimutagenic effect of royal jelly was assayed by a standard testing procedure on Drosophila melanogaster. The similarity of metabolic pathways between Drosophila and mammals makes the test widely applicable for detecting the impact of various potential promutagens and antimutagenic effects could be recognized accordingly. The flies were treated with the potent mutagen MMS, alone and combined with royal jelly. The frequency of sterile males and sex linked recessive lethal mutations increased significantly after MMS treatment and decreased after combined treatment. The results strongly indicate that, in addition to its well documented action on development, life-span and reproductive ability, royal jelly has an antimutagenic potential as well.Antigenotoksični i antimutageni efekat pčelinjeg mleča ispitivan je korišćenjem standardne procedure testiranja pomoću Drosophilae melanogaster. Sličnost metaboličkih puteva između Drosophila i sisara čini ovaj test široko primenljivim u otkrivanju uticaja različitih potencijalnih mutagena i promutagena, a analogno tome se može ispitivati i mogući antimutageni potencijal substanci. Mušice odgovarajućeg genotipa tretirane su jakim mutagenom, metil-metan-sulfonatom (MMS), samostalno i u kombinaciji sa mlečom. Učestalost sterilnih mužjaka i polno vezanih recesivnih letalnih mutacija rasla je značajno nakon tretmana sa MMS i opadala nakon kombinovanog tretmana. Dobijeni rezultati značajno ukazuju da uz već potvrđeni uticaj na razviće, dužinu života i reproduktivnu sposobnost, mleč ima i antimutageni potencijal.Projekat ministarstva br. 152

New mathematical modeling techniques and chromatographic response functions in chemometrical advancement of luquid chromatographic method development

Primena hemometrijskih tehnika u razvoju metoda tečne hromatografije omogućava da se iz minimalanog broja inicijalnih eksperimenata modeluje ponašanje sistema u funkciji različitih faktora i da se zatim, kreirajući odgovarajuće algoritme, generiše veliki broj simuliranih hromatograma koji će omogućiti automatizovano pretraživanje eksperimentalnog prostora s ciljem pronalaženja optimalnih rešenja. Ovaj proces je u potpunosti zavistan od adekvatnosti definisanog matematičkog modela kao i od odabira funkcije cilja. U ovoj disertaciji predlaže se nova funkcija hromatografskog odgovora kao funkcija cilja u optimizacionim procedurama. Funkcija je dizajnirana tako da procenjuje, istovremeno, kvalitet razdvajanja i ukupnu dužinu trajanja hromatografske analize. Individualni članovi funkcije definisani su tako da omoguće maksimalnu pouzdanost merenja kvaliteta hromatograma, a težinski koeficijenti koji su dodati u dizajn funkcije omogućavaju postavljanje željene ravnoteže između individualnih ciljeva. Funkcija je testirana poređenjem sa šest prethodno razvijenih funkcija hromatografskog odgovora na seriji simuliranih hromatograma i eksperimentalno dobijenih u sistemu reverzno–fazne tečne hromatografije (RP–LC) i tečne hromatografije hidrofilnih interakcija (HILIC). Nakon verifikacije adekvatnosti funkcije cilja da karakteriše hromatogram u celini, novorazvijena funkcija inkorporirana je u metodologiju eksperimentalnog dizajna za optimizaciju metoda za analizu smeše raloksifen hidrohlorida i njegovih nečistoća u RP–LC sistemu, kao i smeše agonista i antagonista beta receptora u HILIC sistemu. Za optimizaciju u oba slučaja primenjen je centralni kompozicioni dizajn. Novorazvijena funkcija hromatografskog odgovora modelovana je i praćena kao jedini odgovor sistema, a optimum je definisan primenom metodologije površine odgovora. U nastavku istraživanja funkcija je unapređena tako, da osim kvaliteta razdvajanja i dužine trajanja analize, ima sposobnost da proceni oblik dobijenih pikova što može biti od velikog značaja u farmaceutskoj analizi jer je otežana kvantifikacija pikova neadekvatnog oblika...The application of chemometrical techniques in liquid chromatographic method development enables modeling of system behavior dependence on several factors after performing minimal number of experiments. Further on, by creating the appropriate algorithms, the large number of simulated chromatograms is constructed providing automatized experimental space search and identification of optimal solutions. This process is completely dependent on the accuracy of defined mathematical model and chosen objective function. This dissertation proposes a new chromatographic response function for optimization strategies. The function is designed to simultaneously estimate the quality of separation and the total analysis duration. Individual function terms are defined to provide maximal reliability in chromatograms quality evaluation and weighting factors are added to enable the proper adjustment of balance between individual goals. The function is compared with six previously developed chromatographic response functions on set of simulated chromatograms and experimentally obtained chromatograms in reversed–phased liquid chromatography (RP–LC) and hydrophilic interaction liquid chromatography (HILIC). After the function ability to estimate the chromatograms adequately had been confirmed, it was incorporated in Design of experiments methodology for the optimization of method for the analysis of raloxifene hydrochloride and its impurities in RP–LC system, as well as mixture of agonists and antagonists of beta receptors in HILIC system. The optimization in both cases is performed applying central composite design. The newly developed function was the only output of the system and the optimum is located by response surface methodology. Further on, the function is improved to estimate the peak shape along with separation quality and analysis duration. This is very important in pharmaceutical analysis since the quantification of peaks of inadequate shape is very difficult. Improved function is verified on a set of experimentally obtained chromatograms acquired in the analysis of antidepressants in HILIC system and subsequently applied for method optimization..

Kinetics and the effect of mechanical methods on improving of cross-flow microfiltration and ultrafiltration of synthetic fruit juice.

Fokus ove doktorske disertacije je ispitivanje unakrsne mikrofiltracije i ultrafiltracije. Jedan od glavnih problema pri izvođenju ovih procesa je opadanje fluksa permeata tokom vremena. Svi fenomeni koji dovode do opadanja fluksa permeata obuhvaćeni su fenomenom koncentracione polarizacije i fenomenom „prljanja” membrane...The focus of this doctoral dissertation is the research of cross-flow microfiltration and ultrafiltration. One of the main problems in performing these processes is the decline in flux permeate over time. All phenomena that lead to the decrease in flux permeate are covered by the phenomenon of concentration polarization and the phenomenon of membrane fouling..

Pray drying process characterization and modelling in the solid dosage forms development by application of quality by design concept

Koncept dizajniranja kvaliteta predstavlja sistematski pristup farmaceutskom razvoju proizvoda koji podrazumeva procenu, unapređenje razumevanja i optimizaciju formulacije i proizvodnog procesa kombinovanom primenom prethodnog znanja, analize rizika i izvođenja eksperimenata. Tehnologija sušenja raspršivanjem našla je primenu u farmaceutskoj industriji zahvaljujući jednostavnosti i fleksibilnosti procesa, kao jednostepeni proces kojim se tečnost pretvara u prašak čije se brojne osobine mogu kontrolisati manipulacijom procesnih promenljivih. Razumevanje kako promene procesnih parametara mogu uticati na fizičkohemijske osobine dobijenog proizvoda posebno je važno u proizvodnji čvrstih doziranih oblika koja ima za cilj obezbeđenje predviđanja i kontrole performansi. Cilj ovog istraživanja je unapređenje razumevanja sušenja raspršivanjem kroz karakterizaciju i modelovanje procesa, primenom koncepta dizajniranja kvaliteta. Istraživanje se sastoji iz dva dela sa ciljevima: razvoja procesa sušenja raspršivanjem kao tehnologije pogodne za obezbeđivanje homogenosti praškova i, posledično, ujednačenosti doziranja nisko doziranih lekovitih supstanci (model supstanca naratriptan hidrohlorid); i razvoja procesa sušenja raspršivanjem u postupku proizvodnje praška sa teško rastvorljivim model supstancama, u cilju poboljšanja rastvorljivosti formiranjem kompleksa sa ciklodekstrinima (model supstance vorikonazol i aripiprazol). Istraživanje takođe obuhvata ispitivanje mogućnosti primene dva derivata beta-ciklodekstrina: 2-hidroksipropilbeta- ciklodekstrina (HPBCD) i 2-O-metil-beta-ciklodekstrina (2-O-MBCD) u razvoju formulacije rastvora za raspršivanje sa ciljem poboljšanja rastvorljivosti i brzine rastvaranja odabranih model supstanci. Tokom razvoja, u skladu sa ciljanim profilom praška kao međuproizvoda definisanom u smislu kvaliteta, identifikovani su kritični atributi kvaliteta međuproizvoda, zatim definisani kritični atributi kvaliteta ulaznih parametara (osobine materijala, procesni parametri) i određivane su njihove funkcionalne veze sa kritičnim atributima kvaliteta proizvoda. U prvom delu istraživanja ispitivani su efekti procesnih parametara sušenja raspršivanjem (temperatura ulaznog vazduha, brzina pumpe, brzina aspiratora, koncentracija rastvora) na karakteristike procesa i kompozitnog praška naratriptan/laktoza/maltodekstrin (proizvodni prinos, sadržaj vlage i srednja veličina čestica). U drugom delu istraživanja sprovedene su studije rastvorljivosti teško rastvorljivih model supstanci sa ciklodekstrinima, simulacije molekularnog vezivanja, izvršena je karakterizacija praškova dobijenih sušenjem raspršivanjem rastvora lek:ciklodekstrin. Na odabranoj formulaciji sa aripiprazolom i HPBCD, izvršena je karakterizacija i modelovanje sušenja raspršivanjem. Ispitivani su efekti procesnih parametara sušenja raspršivanjem (temperatura ulaznog vazduha, brzina pumpe, koncentracija rastvora) na karakteristike procesa i kompozitnog praška lek:ciklodekstrin (proizvodni prinos, sadržaj vlage). U karakterizaciji i modelovanju procesa primenjeni su eksperimentalni dizajn, metodologija površine odgovora (RSM) i veštačka neuronska mreža tipa višeslojnog perceptrona (MLP). Primena frakcionog faktorijalnog dizajna (24-1) kao skrining metode omogućila je procenu značajnosti ispitivanih parametara, na osnovu koje je iz daljeg istraživanja isključena brzina aspiratora. Primena centralnog kompozitnog dizajna (CCD), RSM i MLP omogućila je modelovanje i karakterizaciju procesa sušenja raspršivanjem ispitivanih formulacija sa sve tri model supstance, tako što su razvijeni značajni modeli (p-vrednost<0.05)...Quality by design concept represents systematic approach to pharmaceutical product development which consists of assessment, improvement of formulation and process understanding and optimization by combined use of previous knowledge, risk analysis and experimental work. Spray drying technology has found its use in pharmaceutical industry thanks to process simplicity and flexibility, as a single-step process in which liquid is transferred into powder with properties easily controlable by process variables manipulation. Understanding how changes in process parameters can influence the physicochemical properties of resulting product, is especially important in production of solid dosage forms where assurance of predictions and control of performance are the main goals. Main goal of this research is spray drying understanding improvement through process characterization and modelling performed by quality by design concept. The research consists of two sections with following goals: spray drying process development as technology suitable for providing homogeneous powders and subsequently, dose uniformity of low-dose drug substances (model substance naratriptan hydrochloride); and spray drying process development in production of powders with poorly soluble drug substances (model substances voriconazole and aripiprazole). The research is also dealing with examination of potential use of two beta-cyclodextrin derivatives: 2- hydroxypropyl-beta-cyclodextrin (HPBCD) and 2-O-methyl-beta-cyclodextrin (2-O-MBCD) for the purpose of solubility and dissolution improvement of selected model substances. Within the development process, according to quality target product profile for powder as a intermediate product, critical product quality attributes were identified, and then critical quality attributes for input parameters (material properties, process parameters) were defined and their functional relationships with critical product quality attributes were determined. In first section of research, effects of spray drying process parameters (inlet air temperature, pump speed, aspirator, feed concentration) on process and powder characteristics (production yield, moisture content and mean particle size) were examined. In the second section of research solubility studies with poorly soluble substances and cyclodextrins were conducted, as well as molecular docking simulations, and characterisation of spray dried drug:CD powders was performed. For selected formulation with aripiprazole and HPBCD, spray drying process characterisation and modelling was performed. Effects of spray drying process parameters (inlet air temperature, pump speed, feed concentration) on process and powder characteristics (production yield and moisture content) were examined. Design of experiments, response surface methodology (RSM) and artificial neural networks multilayer perceptron (MLP) were used in process characterisation and modelling. Fractional factorial design (24-1) applied as a screening method enabled examined parameters significance assessment, based on which parameter aspirator was excluded from further study. Use of central composite design (CCD), RSM and MLP helped in spray drying process characterisation and modelling for formulations with all threee model drug substances, and significant models were developed (p-value<0.05). RSM results analysis resulted in definition of functional relationships between input parameters and monitored responses. In case of naratriptan hydrochloride and aripiprazole formulation, observations were similar. Parameter that had the greates influence on each investigated response was pump speed..

Noninvasive research of arterial splanchnic circulation in liver cirrhosis:correlation with serum nitric oxide (NO) and ammonia

Hiperdinamski splanhnicni i sistemski protok krvi je tipican za bolesnike sa cirozom jetre. Kombinacija arterijske vazodilatacije i povecanog intravaskularnog volumena je neophodna za potpuno ispoljavanje hiperdinamskog cirkulatornog stanja. Ciroza jetre je udružena sa perifernom vazodilatacijom koja je posledica efekata sistemskih vazodilatatornih supstanci, zbog cega je ciroza jetre sistemska bolest. Mnoge vazoaktivne supstance ucestvuju u nastanku portne hipertenzije. Meu njima, azot-monoksid (NO) je kljucni medijator koji, paradoksalno, reguliše sinusoidnu (intrahepaticku) i sistemsku/splanhnicnu cirkulaciju. Osnovni ciljevi ove doktorske disertacije bili su: 1. Merenje nivoa azotnih produkata metabolizma, kao potentnih vazo-aktivnih medijatora: serumskog azot-monoksida (NO) i serumskog amonijaka (NH3) kod bolesnika sa cirozom jetre i zdravih kontrola. 2. Pokazati promene NO i NH3 u odnosu na klinicke parametre kod bolesnika sa cirozom jetre. 3. Poreenje vrednosti serumskog NO i NH3 sa podacima izmerenih protoka krvi u visceralnim krvnim sudovima jetre, bubrega, slezine i creva kod bolesnika sa cirozom jetre u poreenju sa zdravim kontrolama (ultrasonografska merenja takoe ukljucuju merenje dijametra krvnih sudova, brzine protoka krvi i zapreminski protok). Ucesnike ove prospektivne studije cinilo je 70 pacijenata sa prethodno dijagnostikovanom cirozom jetre, sa i bez ascitesa, koji su leceni u Urgentnom centru KCS, na Klinici za gastroenterologiju i hepatologiju KCS i ambulantno u Hepatološkoj ambulanti Klinike za gastroenterologiju i hepatologiju KCS. Vazodilatatorni fenomen se ispitivao na osnovu merenja lumena i protoka u splanhnicnim arterijama (a.hepatica, a.lienalis, a.renalis, a.mesenterica superior) metodom ultrasonografije i kolor Doppler tehnikom. Kod svih pacijenata su bila uraena neinvazivna ispitivanja koja su obuhvatala: merenje nivoa NO i NH3 u serumu bolesnika sa cirozom jetre..