Traditional drug discovery strategies are usually focused on occupancy of binding sites that directly affect functions of proteins. Hence, proteins that lack such binding sites are generally considered pharmacologically intractable. Modulators of protein activity, especially inhibitors, must be applied in appropriate dosage regimens that often lead to high systemic drug exposures in order to maintain sufficient protein inhibition in vivo. Consequently, there is a risk of undesirable off-target drug binding and side effects. Recently, PROteolysis TArgeting Chimera (PROTAC) technology has emerged as a new pharmacological modality that exploits PROTAC molecules for induced protein degradation. PROTAC molecule is a heterobifunctional structure consisting of a ligand that binds a protein of interest (POI), a ligand for recruiting an E3 ubiquitin ligase (an enzyme involved in the POI ubiquitination) and a linker that connects these two. After POI-PROTAC-E3 ubiquitin ligase ternary complex formation, the POI undergoes ubiquitination (an enzymatic post-translational modification in which ubiquitin is attached to the POI) and degradation. By merging the principles of photopharmacology and PROTAC technology, photocontrollable PROTACs for spatiotemporal control of induced protein degradation have recently emerged. The main advantage of photocontrollable over conventional PROTACs is the possible prevention of off-target toxicity thanks to local photoactivation.

ISSN 2620-0406 Citation: Šikman, M. M, & Grujić, M. (2021). Relationship of AntiMoney Laundering Index with GDP, financial market development, and Human Development Index. NBP. Nauka, bezbednost, policija, 26(1), 21–33. doi:10.5937/nabepo26-29725 Abstract: Money laundering has a direct impact, among other things, on the economic development of a country. The aim of this research is to determine the correlation between money laundering and economic development expressed through GDP, as well as between financial market development (FDI) and the Human Development Index (HDI). The results of the research show that there was a significant relationship between the observed variables, i.e. that there is a relation of the Anti-Money Laundering Index (AMLI) on GDP, financial market development and the HDI. Namely, given that medium-strong links between the observed variables have been established, it can be claimed that there is reason to believe that “copying the behaviour” of a certain country in the fight against money laundering can further develop the financial market, influence human development or an increase in GDP per capita. In particular, a decrease in the AMLI was expected to increase the FDI (R2 = 0.2601). A decrease in the AMLI was expected to increase the HDI (R2 = 0.5747). In that way, financial institutions are directly affected, which negatively relates to economic and political stability.

This paper presents an empirical verification of the effectiveness and usefulness of investment diversification using the main stock exchange indices and Bitcoin. The objective is to determine the effects applying the Markowitz portfolio optimization theory, i.e., the advantages of applying the modern portfolio theory for institutional investors. The research offers an answer to the following question: what are the advantages and disadvantages of using Bitcoin in portfolio optimization? The paper contributes to the representation of the reach and limitations of the modern portfolio theory for institutional investors. The conclusion is that rational behaviour of institutional investors requires consideration of portfolio optimization using the Markowitz model, because it is possible to create portfolios which, on the basis of historical returns, provide desired returns alongside certain risks. The methodology includes the analysis of high frequency data, i.e., daily trading data were used. The results indicate that the use of the Markowitz portfolio selection method, with all its limitations, is desirable, possible and applicable, but that it entails serious flaws in the sense of neglecting transaction costs, foreign exchange differences and the real value in the stock market. The results of the research show that Bitcoin is a good source of diversification in a portfolio that contains traditional financial instruments both for the risk-averse investor as well as for those investors who have a greater appetite for risk. The conclusion is that rational behavior of institutional investors requires consideration of investing in Bitcoin using the Markowitz model. However, given the high degree of volatility, investors should be very careful when making decisions about including Bitcoin in the portfolio.

Cardiovascular diseases are known to be treated with anticoagulants lifelong. Warfarin is one of the most commonly used medications for anticoagulation despite causing serious side effects in some patients. Different single nucleotide polymorphisms (SNPs) that have a role in the cytochrome P450 system can also affect the metabolism, as well as dosing, of warfarin. The purpose of this review is to look into the prevalence of this SNP in the past research and screen for possible correlations with age, place of origin, family history of cardiovascular and cerebrovascular diseases, or other medical conditions possibly present in various populations. In total, 20 scientific articles falling under the inclusion criteria were reviewed and found usable, and the rest of the cases will be highly beneficial in the upcoming years to determine the role of the recently discovered CYP4F2 rs2108622 variant, as well as the previously known CYP2C9 and VKORC1 SNPs, in the variance of warfarin dose requirement. These findings may also point researchers in the right direction for qualifying and validating these genetic variants for use as GBs (genomic biomarkers) in the clinical and medical practice of treatment with warfarin.

Coronary artery disease remains among the leading causes of morbidity and mortality in the world. Percutaneous coronary interventions PCI have become the leading mode of revascularization in patients with single-vessel or double-vessel coronary disease, as well as in patients with acute coronary syndrome. For the purpose of optimal treatment of patients in the Republic of Srpska, a cath lab was opened at the Clinic for Cardiovascular Diseases of the University Medical Center of the Republic of Srpska in June 2007. Retrospective data collection in the period from 2007 to 2021 revealed that 33,183 procedures were performed. The opening of the cath lab of the Clinic for Cardiovascular Diseases of the University Medical Center of the Republic of Srpska enabled the application of the most modern methods for diagnosis and treatment of ischemic coronary heart disease, which led to significantly lower mortality rates from STEMI and NSTEMI infarction in Republika Srpska, with significant progress in treating patients with other forms of ischemic heart disease.

We present a case of 55-years old man with severe mitral regurgitation with significantly reduced ejection fraction, paroxysmal atrial fibrillation and hypertension, who underwent surgical procedure of the replacement of the mitral valve.

We present a case of 72-years old patients with long standing heart failure with reduced ejection fraction, diabates mellitus with chornic renal failure and previous CRT implantation, in whom initation of new treatment with empaglifozine and sacubitril valsartin in addition to beta-blockers and diuretics significantly improved hic clinical condirion and laboratory status.

There is no doubt that examples from folklore have useful, functional and aesthetic value in music teaching, and that it is preferable to use them for educational purposes. Selected examples of folk songs from Montenegro have their own frame and way of musical thinking, which is not always adaptable to musical didactics in terms of notation standards. However, they are adapted and still show that folk songs can be interpolated into the system of music education. From the selected examples of folk songs from Bosnia and Herzegovina, only a small number of examples can be used for illustration, but not for solving specific elements. The notation of Bosnian sevdalinka often contains a series of passing tones that are the result of freedom of interpretation, as well as unresolved metro-rhythmic elements that are not compatible with elementary notation standards.

The family is the basic cell of every society; in it the life of an individual rises, develops and disappears. Family relations are the basis of every social and state system. As a result, all state systems have been trying to keep family relations in peace for centuries. The death of a family member is one of the many factors that can disrupt family harmony, especially under the additional influence of property rights. Centuries ago, the issue of the testator's property was regulated by customary law, and then by legislation. The paper deals with the institute of bequest, as one of the forms of inheritance, with special reference to the types of bequests in the Republic of Serbia. For centuries, bequest has been the institutional of transferring the property and legal relations of the testator to the heirs. The will as we know it today in its form has its basis in Roman law, which had a great influence on the first European civil codes, the Civil Code and the Austrian Civil Code. These codes are still in use today, and their special significance is that they are a panda to all later adopted civil codes, ie to all later established civil legal bases. The Austrian Civil Code had a dominant influence on the settings of the regulation of civil law in the Republic of Serbia. Today, there are nine types of bequests. Each of them follows the life situations, circumstances and circumstances in which it arises.

Inheritance law is a set of legal norms that regulate the property and legal relations of the testator after his death. The fact of death has haunted all social communities for centuries. The loss of a family member affected community members (family) both emotionally and property-wise. After the death of the testator, his property and legal assets remain, the significance of which is reflected on the heirs as well as on third parties, but also on the state as a successor in case of absence of the heirs. The paper deals with the legal regulation of two legal institutes: the contract on lifetime support and the contract on assignment and distribution for life. The paper follows their legislation with reference to certain issues of practice, legal and ethical dilemmas, and in the very conclusion, in parallel with the legal analysis of these two institutes, which by all their characteristics are characterized as legal obligations. These two contracts are the rights of business that have been present in social systems for centuries, their existence and significance have been minimized, and only in modern times have their legal regulations been obtained. Guided by the fact that they are "new" legal institutes, as well as by the fact that the practice, especially during the 90s of the last century, indicated and showed that these first two institutes are suitable for abuse of legislation, the paper addressed the issues of who and when can be a contracting party. , what are the prejudices of the contract, as well as the circumstances when and why they can be null and void, disputed in court or terminated. Man was born manipulative and easy, and the law, and the law, the state and the entire legal system are there to channel it and sanction bad motives, in order to realize an orderly democratic social system, and thus preserve the family as the basic cell of society.

Violence against children is a dynamic, changing social phenomenon. Every society, regardless of the level of development of democracy, economic and political development, regardless of the level of protection of human rights, encounters violence against children on a daily basis. The first professional interests in violence against children were made between the two world wars, but the first active measures to oppose it appeared in the mid-sixties of the twentieth century, in the most developed countries. In the 21st century, the countries of the "third world" remain in a civilizational, cultural, value cocoon. No matter how impossible and imaginary it may seem, in some countries, violence against children is still denied as a social phenomenon and a deviation. The negation of violence does not stem from the circumstance that the child is not physically and mentally punished, but that this "punishment" is justified for the purpose of good upbringing, tradition and similar found excuses. For many years, this attitude has been held in many post-communist states, states that have been isolated for decades, either because of politics or because of religion. However, with the globalization of society, the inevitable opening of borders, but also under great assets whose affirmation of ordinary organizations, primarily at the global and then at the state level, the topic of "violence against children" slowly gained its epilogue. Today, in 2021, violence against children is an open topic in most communities. There are no more taboos. And no turning heads from violence. Of course, there are exceptions, but the world is full of rules with some exceptions. The paper deals with two aspects: global and national, specifically the Republic of Serbia. The paper deals with the definition of the concept of the child, types of violence, legal acts regulating the rights of the child, applied measures, but also proposals for measures and moves to take exceptions (those who deny the existence of violence against children, those who it doesn't matter…) be if not zeroed, and at least minimized.