Built environment fractality as a criterion of space management

U skladu sa holografskom paradigmom univerzuma, novija istraživanja ukazuju na važnost fraktalnosti ljudskog okruženja za njegovo mentalno i fizičko dobro stanje. Primjeri starijih naselja, gdje je fraktalni koncept primjenjen, pokazuju da je u prošlosti postojala svijest o tome, a koja je u konvencionalnim metodama planiranja gradova zaboravljena. Nedostatak hijerarhičnosti i čovjekomjerne razmjere, geometrijski pravilni oblici i zaravnjene linije modernih gradova, vezuju se za negativne društvene pojave. Stoga ovaj rad ima za cilj da ukaže na važnost fraktalnosti građene sredine i da predloži mogućnosti njenog korišćenja kao kriterijuma upravljanja prostorom.In accordance with the holographic paradigm of the universe, recent studies indicate the importance of fractality of the human environment for his mental and physical well-being. There was awareness of that in the past, but the conventional methods of planning cities have forgotten that. The lack of hierarchy and human scale in modern cities, as so as its geometrically regular shapes and flattened lines, are associated with some negative social phenomena. Therefore, this paper aims to highlight the importance of fractality of built environment and to suggest the possibilities of its use as a criterion of space management

Built environment fractality as a criterion of space management

U skladu sa holografskom paradigmom univerzuma, novija istraživanja ukazuju na važnost fraktalnosti ljudskog okruženja za njegovo mentalno i fizičko dobro stanje. Primjeri starijih naselja, gdje je fraktalni koncept primjenjen, pokazuju da je u prošlosti postojala svijest o tome, a koja je u konvencionalnim metodama planiranja gradova zaboravljena. Nedostatak hijerarhičnosti i čovjekomjerne razmjere, geometrijski pravilni oblici i zaravnjene linije modernih gradova, vezuju se za negativne društvene pojave. Stoga ovaj rad ima za cilj da ukaže na važnost fraktalnosti građene sredine i da predloži mogućnosti njenog korišćenja kao kriterijuma upravljanja prostorom.In accordance with the holographic paradigm of the universe, recent studies indicate the importance of fractality of the human environment for his mental and physical well-being. There was awareness of that in the past, but the conventional methods of planning cities have forgotten that. The lack of hierarchy and human scale in modern cities, as so as its geometrically regular shapes and flattened lines, are associated with some negative social phenomena. Therefore, this paper aims to highlight the importance of fractality of built environment and to suggest the possibilities of its use as a criterion of space management

Application of fractal geometry in urban pattern design

Fraktalna geometrija proučava objekte koje karakterizira ponavljanje istih principa raspodjele elemenata promatranjem na više nivoa, a to se prepoznaje u slučaju gradova. Budući da holistički pristup planiranju uključuje uvođenje novih procesa i postupaka u odnosu na razmatranje svih relevantnih faktora koji mogu utjecati na izbor rješenja gradskog obrasca, naglašavamo koliko je za ljudsko blagostanje potrebna svijest o važnosti fraktalnosti u prirodnom i izgrađenom okolišu. U ovom radu podsjećamo na fraktalnost gradskog okoliša kao kvalitete urbanog područja i ističemo nedostatke uobičajenih koncepata planiranja, koji ne uzimaju u obzir fraktalnost obrasca kao kriterij za poboljšanje okoliša. Nakon kratkog pregleda osnova fraktalne teorije i prethodnih istraživanja, predstavljamo ranije poznate mogućnosti i sugeriramo nove za primjenu fraktalne geometrije u projektiranju gradskog obrasca.Fractal geometry studies the structures characterized by the repetition of the same principles of element distribution on multiple levels of observation, which is recognized in the case of cities. Since the holistic approach to planning involves the introduction of new processes and procedures regarding the consideration of all relevant factors that can influence the choice of urban pattern solutions, we point to the awareness of the importance of fractality in natural and built environment for human well-being. In this paper, we have reminded of the fractality of urban environment as a quality of an urban area and pointed on the disadvantages of conventional planning concepts, which do not consider pattern fractality as criterion for environmental improvement. After a brief review of the basis of fractal theory and the review of previous studies, we have presented previously known and suggested new possibilities for the application of fractal geometry in urban pattern design

Potential anti-melanoma activity of Imidazoline I1 receptor agonists

Melanoma is the deadliest form of skin cancer. Despite the advancements in targeted BRAF and MEK therapy and immunotherapies, metastatic melanoma patients still have poor prognosis with a median survival of 9 months and a long-term survival rate of 10%. There is an urgent need for novel treatment modalities that target metastatic melanoma. Imidazoline I1 receptor (IR1, IRAS, NISCH) is a scaffolding protein that has been shown to be a tumor suppressor in breast cancer through regulation of cancer cell survival, motility and invasion. IR1 role in metastatic melanoma has not been investigated to date. Of importance, several IR1 agonists are clinically approved for treatment of hypertension. The aim of this study was to examine the IR1 expression in melanoma and the effects of IR1 agonists on melanoma cell viability. To confirm the target expression, we first determined IR1 levels in primary and metastatic melanoma patient samples by qRT-PCR and immunohistochemistry. We found that it is expressed in primary tumors and liver metastases and, to a lesser extent, in metastatic lymph nodes. Next, we examined the activity of IR1 agonists – rilmenidine, clonidine and moxonidine – in a panel of metastatic melanoma cell lines (HTB140, FemX-1, A375 and 518a2) and found that rilmenidine most potently inhibited cell viability. Notably, it was not toxic towards human dermal fibroblasts and keratinocytes. Furthermore, rilmenidine time- and dose- dependently induced cell cycle arrest in G2/M phase and consequent apoptosis. Our results imply that imidazoline I1 receptor is potentially novel anti-melanoma target, and that its already clinically approved agents have promising anti-cancer activity

Nischarin expression may have differing roles in male and female melanoma patients

Due to the development of resistance to previously effective therapies, there is a constant need for novel treatment modalities for metastatic melanoma. Nischarin (NISCH) is a druggable scaffolding protein reported as a tumor suppressor and a positive prognostic marker in breast and ovarian cancers through regulation of cancer cell survival, motility and invasion. The aim of this study was to examine the expression and potential role of nischarin in melanoma. We found that nischarin expression was decreased in melanoma tissues compared to the uninvolved skin, and this was attributed to the presence of microdeletions and hyper-methylation of the NISCH promoter in the tumor tissue. In addition to the previously reported cytoplasmic and membranous localization, we observed nischarin in the nuclei in melanoma patients’ tissues. NISCH expression in primary melanoma had favorable prognostic value for female patients, but, unexpectedly, high NISCH expression predicted worse prognosis for males. Gene set enrichment analysis suggested significant sex-related disparities in predicted association of NISCH with several signaling pathways, as well as with different tumor immune infiltrate composition in male and female patients. Taken together, our results imply that nischarin may have a role in melanoma progression, but that fine-tuning of the pathways it regulates is sex-dependent.This is the submitted version of the article: Ostojić, M.; Jevrić, M.; Mitrović-Ajtić, O.; Živić, K.; Tanić, M.; Čavić, M.; Srdić-Rajić, T.; Grahovac, J. Nischarin Expression May Have Differing Roles in Male and Female Melanoma Patients. J Mol Med 2023, 101 (8), 1001–1014. https://doi.org/10.1007/s00109-023-02339-y

Primena metaheuristika na optimizaciju raspodele opterećenja kod mašinskih elemenata i sklopova

In this Phd thesis, heuristic, meta-heuristic and predictive methods are considered. Meta-heuristics optimisation of the transverse load distribution factor of helical and spur gears is conducted. The multi-objective optimisation problem of the planetary gear train is done using Genetic Algorithm method. A comparative study of several meta-heuristic methods is given for solving the problem of dynamic load capacity and working life at radial ball bearings. Bayesian network, as a predictive method, is implemented in the software to support the decision making in complex mechanical plants.Докторска дисертација се бави темама везаним за хеуристичке, метахеуристичке и предикционе методе. Извршена је метахеуристичка оптимизација проблема трансверзалног фактора расподеле оптерећења код цилиндричног зупчастог пара. Вишекритеријумски проблем геометрије планетарног преносника је решаван применом генетских алгоритама. Поређење неколико метахеуристичких метода је дато на решавању оптимизационог проблема радног века и динамичке носивости код котрљајних кугличних лежаја. Бајесове мреже, као предикциона метода, су уграђене у софтвер за подршку одлучивању у комплексним машинским постројењима.Doktorska disertacija se bavi temama vezanim za heurističke, metaheurističke i predikcione metode. Izvršena je metaheuristička optimizacija problema transverzalnog faktora raspodele opterećenja kod cilindričnog zupčastog para. Višekriterijumski problem geometrije planetarnog prenosnika je rešavan primenom genetskih algoritama. Poređenje nekoliko metaheurističkih metoda je dato na rešavanju optimizacionog problema radnog veka i dinamičke nosivosti kod kotrljajnih kugličnih ležaja. Bajesove mreže, kao predikciona metoda, su ugrađene u softver za podršku odlučivanju u kompleksnim mašinskim postrojenjima

A multi-aspect approach to energy retrofitting under global warming

An average working individual in today\u27s society spends a considerableamount of a typical day in an office environment. This, in turn,can negatively influenceher or his circadian systemif the indoor builtenvironment is not designed to provide adequate luminous conditions. Therefore, the presented paper\u27s main objectivewas to address the extent to whichindoor built environmentparametersinfluence the characteristics of the indoornon-visual and visualluminousenvironment.To answer the stated question,a statistical analysis of parametric simulationsusing multispectral software ALFAwas carried outfora sample cellular office in Ljubljana, Slovenia.The influence ofroom, geometrical(depth, width,andwindow to wall ratio),and optical (reflectance of walls, ceiling, and floor and glazing transmissivity) parameterswasstudied for four cardinaloccupantviewdirections. The results show thatthe windowis the most influential building element as the windowto wall ratio and glazing transmissivityare the most influential geometricaland optical parameters. However, it was exposedthatthisis not entirely true for occupant positionsdeeper in space and facing away from the window, as the influence of all studied building parameters changes according to theview orientation and positionin relation to the window

Association of uPA and PAI-1 tumor levels and 4G/5G variants of PAI-1 gene with disease outcome in luminal HER2-negative node-negative breast cancer patients treated with adjuvant endocrine therapy

Abstract Background The aim of this study was to evaluate the prognostic potential of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) tumor tissue levels and examine the association between these biomarkers and classical prognostic factors in early node-negative luminal breast cancer patients. The clinical value of 4G/5G variants of PAI-1 gene was evaluated. Patients and methods This study involved 81 node-negative, estrogen receptor-positive and/or progesterone receptor-positive and human epidermal growth factor receptor 2-negative operable breast cancer patients who underwent radical surgical resection and received adjuvant endocrine therapy. Determination of uPA and PAI-1 concentrations in the breast cancer tissue extracts was performed using FEMTELLE® uPA/PAI-1 ELISA. An insertion (5G)/deletion (4G) polymorphism at position − 675 of the PAI-1 gene was detected by PCR-RFLP analysis. Results Our research showed that patients with uPA tumor tissue levels higher than 3 ng/mg of protein had significantly reduced disease-free survival (DFS) and overall survival (OS) when compared to patients with uPA tumor tissue levels lower or equal to 3 ng/mg of protein. Patients with PAI-1 tumor tissue levels higher than 14 ng/mg of protein had significantly decreased OS in comparison with patients with PAI-1 tumor tissue levels lower or equal to 14 ng/mg of protein. ROC analysis confirmed the uPA and PAI-1 discriminative potential for the presence/absence of relevant events in these patients and resulted in higher cut-off values (5.65 ng/mg of protein for uPA and 27.10 ng/mg of protein for PAI-1) than standard reference cut-off values for both biomarkers. The prognostic importance of uPA and PAI-1 ROC cut-off values was confirmed by the impact of uPA higher than 5.65 ng/mg of protein and PAI-1 higher than 27.10 ng/mg of protein on poorer DFS, OS and event-free survival (EFS). We observed that patients with dominant allele in PAI-1 genotype (heterozygote and dominant homozygote, − 675 4G/5G and − 675 5G/5G) had significantly increased DFS, OS and EFS when compared with patients with recessive homozygote genotype (− 675 4G/4G). Conclusion Our study indicates that uPA and PAI-1 tumor tissue levels and 4G/5G variants of PAI-1 gene might be of prognostic significance in early node-negative luminal HER2-negative breast cancer patients treated with adjuvant endocrine therapy