On Solving the Maximum Betweenness Problem Using Genetic Algorithms

In this paper a genetic algorithm (GA) is applied on Maximum Betweennes Problem (MBP). The maximum of the objective function is obtained by finding a permutation which satisfies a maximal number of betweenness constraints. Every permutation considered is genetically coded with an integer representation. Standard operators are used in the GA. Instances in the experimental results are randomly generated. For smaller dimensions, optimal solutions of MBP are obtained by total enumeration. For those instances, the GA reached all optimal solutions except one. The GA also obtained results for larger instances of up to 50 elements and 1000 triples. The running time of execution and finding optimal results is quite short

Genetic Algorithm Approach for Solving the Machine-Job Assignment with Controllable Processing Times

This paper considers a genetic algorithm (GA) for a machine-job assignment with controllable processing times (MJACPT). Integer representation with standard genetic operators is used. In an objective function, a job assignment is obtained from genetic code and for this, fixed assignment processing times are calculated by solving a constrained nonlinear convex optimization problem. Additionally, the job assignment of each individual is improved by local search. Computational results are presented for the instances from literature and modified large-scale instances for the generalized assignment problem (GAP). It can be seen that the proposed GA approach reaches almost all optimal solutions, which are known in advance, except in one case. For large-scale instances, GA obtained reasonably good solutions in relatively short computational time

Neurobiology of Schizophrenia

Složena priroda poremećaja iz spektra shizofrenije nije dopustila nastanak jednostavnih objedinjenih bioloških modela koji bi objasnili točan mehanizam nastanka. Unatoč tome, od samih početaka konceptualizacije tih poremećaja identificirane su jasne strukturne promjene mozga oboljelih s općenitim gubitkom volumena i proširenjem moždanih komora, koje su pokazivale i longitudinalnu dinamiku te imale određenu prediktivnu vrijednost. Neke od navedenih promjena volumena sive tvari povezuju se i sa specifičnim domenama simptoma. Iako postoji više neurokemijskih teorija psihotičnih poremećaja, teorija dopaminske disfunkcije (hiperdopaminergije) u mezolimbičkom putu i dalje se smatra dominantnom i objašnjava nastanak pozitivnih simptoma psihoze te terapijski učinak lijekova koji blokiraju dopaminske D2 receptore. Glutamatna teorija koja se zasniva na mogućoj disfunkciji glutamatnih NMDA receptora te upalna teorija shizofrenije objašnjavaju određene mehanizme koji mogu prethoditi dopaminskoj disfunkciji kao „konačnome zajedničkom putu“ u psihozu. Ništa ne pokazuje složenost prirode poremećaja koliko podaci o genskim lokusima povezanima s rizikom za nastanak shizofrenije. Istraživanja su, u skladu s općeprihvaćenim poligenskim modelom poremećaja, identificirala više od 100 lokusa povezanih s rizikom, među kojima i one koji kodiraju bitne komponente dopaminske i glutamatne neurotransmisije. Zanimljivo je da snažnu povezanost pokazuju lokusi na 6. kromosomu vezani uz sustav uključen u imuni odgovor, potvrđujući na taj način i značajno mjesto upalne teorije shizofrenije. Upalna teorija promatra intrauterine infekcije, ali i kasnije infekcije, kao udarce koji na podlozi postojeće vulnerabilnosti sustava dovode do njegove disfunkcije i nastanka poremećaja. Prema većini prihvaćenih modela, osnova za nastanak poremećaja postoji prenatalno te s naknadnim „udarcima“ tijekom života dovodi do javljanja poremećaja.The complexity of disorders in the schizophrenia spectrum thwarted the emergence of simple unified biological models that would explain the concrete mechanism of their occurrence. However, from the inception of the disorders, distinct structural changes have been identified in patients’ brains. We see an overall loss of volume and enlargement of the cerebral ventricles, which also showed a longitudinal dynamic with certain predictive value. Some volume changes in the gray matter are also associated with specific symptoms. Although several neurochemical theories of psychotic disorders exist, the theory of dopamine dysfunction (hyperdopaminergia) in the mesolimbic pathway still dominates and explains the emergence of positive symptoms of psychosis and the therapeutic effect of dopamine D2 receptor blockers. The glutamate theory based on the possible dysfunction of glutamate NMDA receptors, and the inflammatory theory explain certain mechanisms that may precede dopamine dysfunction as the “final common path” to psychosis. Nothing displays the complexity of the disorder as much as data on gene loci as a risk for developing schizophrenia. Research, in accordance with the generally accepted polygenic model of the disorder, has identified more than 100 risk-related loci, including those encoding essential components of dopamine and glutamate neurotransmission. It is interesting that loci on the 6th chromosome associated with immune response confirm the inflammation model. It sees ITUs and other infections as blows to the already vulnerable system that leads to dysfunction and the emergence of disorders. According to accepted models, disorders exist prenatally and circumstances in life bring about its emergence

Identifying characteristics of thalamo-cortical changes and their relationship with symptoms in schizophrenia [Utvrđivanje obilježja talamo-kortikalnih promjena i njihovog odnosa sa simptomima u shizofreniji]

Hypothesis of the doctoral thesis was that, using resting-state functional magnetic resonance imaging (fMRI), patients diagnosed with schizophrenia would exhibit stable and specific patterns of thalamic connectivity changes that will show different relationship with specific symptoms of psychotic disorders. The aims of the study were to characterize in a more detailed way changes in thalamo-cortical connectivity (over- and under-connectivity) in a clinical sample compared to healthy controls, by using state-of-the-art resting-state functional resonance and Human Connectome Project protocols, as well as to more specifically determine within-thalamus differences and their relative contribution to described connectivity changes. Finally, the aim was to determine relationship between identified connectivity changes and specific symptoms of the disorder. Subjects for the study were pooled from multiple centers, as part of an existing initiative, Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium, created with a goal of investigating intermediate phenotypes across psychotic disorders. Study procedures and data analyses were done under the approved Yale University project Characterizing Clinical and Pharmacological Neuroimaging Biomarkers. Following identification of subjects that passed stringent quality controls for fMRI data, and matching with the clinical and healthy control populations, study included 436 psychosis probands (167 schizophrenia patients, 119 schizoaffective disorder patients, and 150 patients diagnosed with bipolar disorder with history of psychosis) and 219 matched healthy controls. Whole-thalamus seed-based analyses were used to determine thalamic connectivity changes, followed by parcellation of thalamus using a priori defined functional subnuclei, and data-driven clustering, to define details of the thalamo-cortical dysconnectivity in schizophrenia and psychotic disorders. Both in schizophrenia, and in the wider psychosis spectrum, there was a robust pattern of thalamic over-connectivity with sensory and motor regions, as well as with associative areas tasked with integration of lower-level inputs, and under-connectivity with cerebellar regions. Interestingly, previously reported under-connectivity with prefrontal regions was evident only in dorsal attention functional thalamic subnucleus connectivity map. Nine functional thalamic subnuclei showed relatively different thalamic connectivity changes, ranging from altogether missing effects to wide-spread over- /under-connectivity, but overall followed same general dysconnectivity pattern described for the whole thalamus. Clustering analyses revealed that the data-driven clustering, released from constraints of a priori defined thalamic subnuclei, resulted in solutions that significantly differed from existing functional subnuclei or anatomical divisions, with areas centered on mediodorsal nucleus and ventral lateral areas driving the dysconnectivity effect. In schizophrenia, thalamo-cortical connectivity changes showed relationship with negative symptoms, as well as with excitation and disorganization subscale scores, suggesting that a more pronounced over- or under-connectivity effect predicted more pronounced specific symptoms. Under-connectivity effect of the dorsal attention functional subnucleus (including reduced connectivity with prefrontal cortical regions) also correlated with disorientation. In conclusion, thalamo-cortical dysconnectivity patterns of seemingly correlated over- and under-connectivity effects seems to be robustly present in schizophrenia, but also across the psychosis spectrum. Although the same general pattern exists across different thalamic regions, its extent differs among different thalamic functional subnuclei suggesting that the effect is driven by specific associative functional subnuclei. Finally, although thalamo-cortical connectivity changes might be linked to a more non-specific disease severity or trait indicators, negative symptoms, disorganization, and excitation seem to be connected more directly to those changes than positive symptoms or emotional dysregulation

Neurobiology of Schizophrenia

Složena priroda poremećaja iz spektra shizofrenije nije dopustila nastanak jednostavnih objedinjenih bioloških modela koji bi objasnili točan mehanizam nastanka. Unatoč tome, od samih početaka konceptualizacije tih poremećaja identificirane su jasne strukturne promjene mozga oboljelih s općenitim gubitkom volumena i proširenjem moždanih komora, koje su pokazivale i longitudinalnu dinamiku te imale određenu prediktivnu vrijednost. Neke od navedenih promjena volumena sive tvari povezuju se i sa specifičnim domenama simptoma. Iako postoji više neurokemijskih teorija psihotičnih poremećaja, teorija dopaminske disfunkcije (hiperdopaminergije) u mezolimbičkom putu i dalje se smatra dominantnom i objašnjava nastanak pozitivnih simptoma psihoze te terapijski učinak lijekova koji blokiraju dopaminske D2 receptore. Glutamatna teorija koja se zasniva na mogućoj disfunkciji glutamatnih NMDA receptora te upalna teorija shizofrenije objašnjavaju određene mehanizme koji mogu prethoditi dopaminskoj disfunkciji kao „konačnome zajedničkom putu“ u psihozu. Ništa ne pokazuje složenost prirode poremećaja koliko podaci o genskim lokusima povezanima s rizikom za nastanak shizofrenije. Istraživanja su, u skladu s općeprihvaćenim poligenskim modelom poremećaja, identificirala više od 100 lokusa povezanih s rizikom, među kojima i one koji kodiraju bitne komponente dopaminske i glutamatne neurotransmisije. Zanimljivo je da snažnu povezanost pokazuju lokusi na 6. kromosomu vezani uz sustav uključen u imuni odgovor, potvrđujući na taj način i značajno mjesto upalne teorije shizofrenije. Upalna teorija promatra intrauterine infekcije, ali i kasnije infekcije, kao udarce koji na podlozi postojeće vulnerabilnosti sustava dovode do njegove disfunkcije i nastanka poremećaja. Prema većini prihvaćenih modela, osnova za nastanak poremećaja postoji prenatalno te s naknadnim „udarcima“ tijekom života dovodi do javljanja poremećaja.The complexity of disorders in the schizophrenia spectrum thwarted the emergence of simple unified biological models that would explain the concrete mechanism of their occurrence. However, from the inception of the disorders, distinct structural changes have been identified in patients’ brains. We see an overall loss of volume and enlargement of the cerebral ventricles, which also showed a longitudinal dynamic with certain predictive value. Some volume changes in the gray matter are also associated with specific symptoms. Although several neurochemical theories of psychotic disorders exist, the theory of dopamine dysfunction (hyperdopaminergia) in the mesolimbic pathway still dominates and explains the emergence of positive symptoms of psychosis and the therapeutic effect of dopamine D2 receptor blockers. The glutamate theory based on the possible dysfunction of glutamate NMDA receptors, and the inflammatory theory explain certain mechanisms that may precede dopamine dysfunction as the “final common path” to psychosis. Nothing displays the complexity of the disorder as much as data on gene loci as a risk for developing schizophrenia. Research, in accordance with the generally accepted polygenic model of the disorder, has identified more than 100 risk-related loci, including those encoding essential components of dopamine and glutamate neurotransmission. It is interesting that loci on the 6th chromosome associated with immune response confirm the inflammation model. It sees ITUs and other infections as blows to the already vulnerable system that leads to dysfunction and the emergence of disorders. According to accepted models, disorders exist prenatally and circumstances in life bring about its emergence

Platinum and ruthenium complexes as promising molecules in cancer therapy

Cancer is one of the most common fatal diseases in humans nowadays. About 20 million new cancer cases are expected in the next two decades worldwide. The development of new chemotherapeutic agents with improved properties is presently the main challenge in the medicinal chemistry. Cisplatin was introduced to oncology in 1978 as first chemotherapeutic agent regarding its specific interaction with DNA, leading to its damage and causing the cell death. Since the first application of cisplatin in cancer therapy, there has been a growing interest in new metal-based compounds, in particular platinum and ruthenium complexes, with better anticancer activity and less side-effects compared to cisplatin. Carboplatin and oxaliplatin have shown promising action against some types of cancer, which are resistant to cisplatin. With the aim to overcome cross-resistance to these Pt(II) drugs, bioavailable platinum complexes (satraplatin and picoplatin) firstly found application as orally administered drugs, as well as some combined therapies of Pt(II) drugs (cisplatin, picoplatin) with specific resistant modulators. In recent years, novel polymer and liposomal formulations of platinum drugs (prolindac, lipoplatin, lipoxal, aroplatin) have been designed with strategy to improve drug delivery to target cancer cells and reduce toxicity. Complexes based on ruthenium have great potential to become leading candidates for the medical use in anticancer therapy. Some of these compounds have shown good anticancer activity, both in vitro and in vivo and two of them (KP1019 and NAMI-A) have passed clinical trials and given promising results

SPECIFICITY OF PERFORMANCE MEASUREMENT IN THE MINISTRY OF DEFENSE AND THE SERBIAN ARMED FORCES

The purpose of this paper is to investigate the specific characteristics of performance measurement on the example of the Ministry of Defense and the Serbian Armed Forces. The calculation of financial and non-financial performance measures of the Ministry of Defense and the Serbian Armed Forces contributes to constant improvement or maximization of their ability to provide goods and services through the effective and efficient acquisition and use of different types of resources. The research was conducted using the data on selected financial and nonfinancial performances from the 31st Infantry Battalion reports in the period from 2012 to 2018. In order to confirm the hypothesis, the method of analysis, the synthesis method and the correlation analysis method were used. The empirical results of this study show that there is a high degree of interdependence between the financial management and control systems, on the one hand, and increased training of people and more adequate maintenance of motor vehicles, weapons and combat techniques, on the other. The main contribution of this paper is to emphasize the importance of performance measurement in the Ministry of Defense and the Serbian Armed Forces and their contribution to creating a certain level of socialwelfare

Solidified waste water treated sludge as partial replacement of cement in concete composites

In this research, tests of mortar and porous concrete made with solidified waste water treatment sludge (SWWTS) used in two forms as a partial replacement of cement were carried out. SWWTS mainly consisted out of CaCO3 and Ca(OH)2, having no pozzolanic properties. For this reason, it was used both, as produced, and modified by adding Al2O3 and Mg3Si4O10(OH)2 in certain percentages. One mortar type and two types of porous concrete were tested. For each of the three products two mixtures were prepared: the reference mixture and the mixture made with 30% replacement of cement, while the other components remained the same. Based on the given comparative analysis, conclusions were drawn regarding the structure of porous concrete slabs, which refer to individual analyzed properties, but also to the possibility of applying energy-efficient materials. The obtained results point to the conclusion that the use of SWWTS reduces the values of almost all tested properties of porous concrete (flexural and compressive strength, pull-off strength, abrasion resistance), but also that the modification of SWWTS led to a smaller difference in the results of the samples made with 30% of cement replacement and the reference samples. Although, the use of SWWTS led to the reduction of mechancal properties of concretes, the most important benefit is development of possible way for reuse of this waste material and avoid its disposal in the landfills