Cyclotides are plant-derived disulfide-rich peptides comprising a cyclic cystine knot, which confers remarkable stability against thermal, proteolytic, and chemical degradation. They represent an emerging class of G protein-coupled receptor (GPCR) ligands. In this study, utilizing a screening approach of plant extracts and pharmacological analysis we identified cyclotides from Carapichea ipecacuanha to be ligands of the κ-opioid receptor (KOR), an attractive target for developing analgesics with reduced side effects and therapeutics for multiple sclerosis (MS). This prompted us to verify whether [T20K]kalata B1, a cyclotide in clinical development for the treatment of MS, is able to modulate KOR signaling. T20K bound to and fully activated KOR in the low μM range. We then explored the ability of T20K to allosterically modulate KOR. Co-incubation of T20K with KOR ligands resulted in positive allosteric modulation in functional cAMP assays by altering either the efficacy of dynorphin A1–13 or the potency and efficacy of U50,488 (a selective KOR agonist), respectively. In addition, T20K increased the basal response upon cotreatment with U50,488. In the bioluminescence resonance energy transfer assay T20K negatively modulated the efficacy of U50,488. This study identifies cyclotides capable of modulating KOR and highlights the potential of plant-derived peptides as an opportunity to develop cyclotide-based KOR modulators.

This paper presents some of our first experiences and findings in the ARPA-E project ReNew100, which is to develop an operator support system to enable stable operation of power system with 100% non-synchronous (NS) generation. The key to 100% NS system, as found in many recent studies, is to establish the grid frequency reference using grid-forming (GFM) inverters. In this paper, we demonstrate in Electro-Magnetic-Transient (EMT) simulations, based on Hawai'i big island system with 100% NS capacity, that a system can be operated stably with the help of GFM inverters and appropriate controller parameters for the inverters. The dynamic security optimization (DSO) is introduced for optimizing the inverter control parameters to improve stability of the system towards N-1 contingencies. DSO is verified for five critical N-1 contingencies of big island system identified by Hawaiian Electric. The simulation results show significant stability improvement from DSO. The results in this paper share some insight, and provide a promising solution for operating grid in general with high penetration or 100% of NS generation.

This paper presents two spheres of public engagement of women in the contemporary society of Bosnia and Herzegovina (BiH): politics and the academic community. An insight into the first sphere, the political one, provides an introductory, succinct overview of the development of societal roles and positions of women during the period of Jugloslawia (1945-1992). Afterward, it focuses on the current position of women in another public sphere, the academic community. The applied method was a test (questionnaire). The first challenge was to determine the exact number of women engaged in the teaching process at the chosen public university in BiH (University of Zenica) since it was not possible to obtain data through the official internet websites or from the relevant published documents. According to these official documents, the total number of employees based on contracts for full-time or piece-work engagements in 2017 was 520. But, these documents did not contain data on the number of men and women who are engaged as teachers. Based on data available on the internet websites of faculties of this University, there were 65 women engaged as teachers; all were full-time employees since these websites did not present persons engaged as teachers on other legal bases. Results confirmed, while women were not taking the managing positions, men were undoubtedly dominant in higher education institutions managing positions. Although women fairly successfully graduate from all three university study cycles, afterward they face the so-called „glass ceiling“, disabling them or making it very hard to officially enter the education institutions as employees, which limits any future advancement. Women who managed to become faculty members were very often faced with gender-based stigmatization and/or segregation. Further analyses should establish why women, as employees of HEIs, hesitate and decline to accept managing positions. Also, it is necessary to enhance the higher education institution’s methodology of reporting, for HEIs to provide clear data on the number of women engaged in the teaching process, and data on their status (assistants or senior assistants, and assistant, associate or full professors). When a total number of women employed as teaching, administrative and technical staff in an HEI is given, the actual state of gender equality in any of the mentioned three segments is presented. The importance of women’s participation in politics becomes also clear in this point since it is extremely important to have political awareness and readiness for solving problems and creating relevant policies for the above issues.

Before the socio-political communities are posted, a very demanding task of defining the subject on whose name will behalf political power is implemented over a given state territory. However, the question about the subject of sovereignty should in no case be misunderstood as an issue of simply theoretical approach. The level of a state’s democracy, as well as its ability to realize internal and external sovereignty, depends entirely on fact: does the power belong to the People and whether it derives from the People. In other words, the issue of popular sovereignty is a substantial, constitutive element of modern democratic states. When we speak about contemporary Bosnia and Herzegovina, the functionality of the entire state government is often hindered by the complex decision-making processes at all state levels which lead to obstruction of the entire decision-making process. Such a dysfunctional decision-making process on the state level poses a threat and disables the Bosnian plural society to respond to the modern challenges of a democratic functioning state. The legal nature of Bosnian society is determined by the existence of constituent people who have “usurped” the entire decision-making process. There is still no end in sight to the struggle that leads to an oligarchy of the ruling elites; furthermore, there is still no appropriate socio-political mechanism that will enhance the accountability of the representatives to their voters; it is still inconceivable that decisions of state authorities are effectively and consistently implemented throughout the national territory. In other words, there is still no appropriate mechanism that will enhance the principle of popular sovereignty. It is necessary to “offer” Bosnia and Herzegovina’s pluralism and its political tradition a form of democratic authority which in no way should be a cliché. Furthermore, it may not be one of the “copy-paste” models of democratic authority. Currently, citizens of B&H are completely suspended (de facto, there are only citizens of entities). In the Federation of Bosnia and Herzegovina Serbs are suspended, while in the Republika Srpska, Bosniacs and Croats cannot equally participate in the decision-making process. An unfinished process of implementation of the Dayton Agreement and, in particular, Annex 4 (the Constitution of B&H), whose provisions permit discrimination against the citizens of Bosnia and Herzegovina (the impossibility of the realization of the principle of equality in the exercise of universal suffrage), as well as the non-application of the Decision of the European Court of Human Rights contributes and is conducive to further segmentation of Bosnian society.

When it comes to providing support to children with disabilities, this role is primarily taken over by the family, and above all by the parents. The research was conducted to determine which protective factors of mental health for parents of children with disabilities facilitate their parenting role. The sample consisted of 17 participants, parents of children with various disabilities who filled out an online questionnaire designed for the needs of the research. The questionnaire was intended to assess the protective factors of the mental health of parents of children with disabilities. The results showed that parents experience moderate to high levels of stress when it comes to their parental role, while they emphasize child care as the main source of stress related to the parental role. They point out social support as one of the leading sources of support, much more often relying on informal sources (family members, friends, neighbors). In addition to social support, significant protective factors include faith in God and personality traits such as patience (calmness), perseverance, strength (resilience), optimism, and hope. Destigmatization also stands out as a significant protective factor, ie the parental role is facilitated by the complete acceptance of the child by the environment. Based on the findings, guidelines and recommendations can be formulated for planning and creating a program to provide support to parents of children with disabilities. In this context, various psychosocial support programs aimed at strengthening parental competencies and protective factors that play an important role in preserving the mental health of parents of children with disabilities would be significant.

With the development of technologies, virtual interaction contributes to the stronger virtual socialization of young people. This paper aims to examine how the virtual world influences the identity of young people. In the introduction, we reviewed the studies that dealt with virtual socialization, and then we presented a brief empirical insight into today’s socialization of young people from 14 to 21 years of age. With the questionnaire, we tried to examine the “quality” of virtual socialization in the lives of young people. The tasks of our research are focused on questioning the values that young people adopt through virtual socialization, an assessment of the “image of their own” that is in the virtual world, and the compatibility of the virtual identity with the one built in the family and peer environment. Respondents expressed views that their lives matched a life that points to social networks, while they felt that their peers did not live a life that they sought to portray on social networks. The results showed that they feel more secure in online communication than in life. Also, opinions are that the values they adopt are influenced by public opinion, etc. We can conclude that educating youths about the virtual world should be in several directions: actuality, truthfulness, privacy, and freedom.

The increasing penetration of inverter-based resources (IBRs) is changing grid dynamics and challenging grid planning, operation, and protection. Particularly, the increasing integration of IBRs may drive the power grid towards weak grid conditions, where potential dynamic stability issues may become significant. Recently, it was reported that the unintended loss of solar generation occurred in Southern California over a large geographic area. One of the major reasons for this generation loss is the tripping of solar generators due to the overvoltage in a less than one cycle time frame (i.e., sub-cycle overvoltage) experienced by solar photovoltaic (PV) inverters, especially when solar PV inverters enter the momentary cessation operation mode in response to abnormal grid disturbances. In this paper, the impact of grid strength on sub-cycle dynamics resulting from momentary cessation is investigated in a power system with distributed solar PV integration. In this investigation, distributed solar PVs are modeled with detailed grid-following inverter models considering inverter switching dynamics and momentary cessation function. It is found that undesired sub-cycle overvoltage has a positive relation to grid strength at points of integration (POIs) of solar PVs. At the weak POIs, server sub-cycle overvoltage occurs not only when momentary cessation starts to cease energy injection but also when momentary cessation restarts to inject energy into the system during the restoration process. Furhtermore, the interaction between solar PVs making POIs weak exacerbates the severity of the sub-cycle overvoltage at the POIs. Thus, in the power system with high penetration of solar PVs, it is important to improve grid strength in power system planning and quickly recover grid strength in power system operation following disturbances.

Data from clinical trials suggest that CT-confirmed nondisplaced scaphoid waist fractures heal with less than the conventional 8–12 weeks of immobilization. Barriers to adopting shorter immobilization times in clinical practice may include a strong influence of fracture tenderness and radiographic appearance on decision-making. This study aimed to investigate (1) the degree to which surgeons use fracture tenderness and radiographic appearance of union, among other factors, to decide whether or not to recommend additional cast immobilization after 8 or 12 weeks of immobilization; (2) identify surgeon factors associated with the decision to continue cast immobilization after 8 or 12 weeks. In a survey-based study, 218 surgeons reviewed 16 patient scenarios of CT-confirmed nondisplaced waist fractures treated with cast immobilization for 8 or 12 weeks and recommended for or against additional cast immobilization. Clinical variables included patient sex, age, a description of radiographic fracture consolidation, fracture tenderness and duration of cast immobilization completed (8 versus 12 weeks). To assess the impact of clinical factors on recommendation to continue immobilization we calculated posterior probabilities and determined variable importance using a random forest algorithm. Multilevel logistic mixed regression analysis was used to identify surgeon characteristics associated with recommendation for additional cast immobilization. Unclear fracture healing on radiographs, fracture tenderness and 8 (versus 12) weeks of completed cast immobilization were the most important factors influencing surgeons’ decision to recommend continued cast immobilization. Women surgeons (OR 2.96; 95% CI 1.28–6.81, p  =  0.011), surgeons not specialized in orthopedic trauma, hand and wrist or shoulder and elbow surgery (categorized as ‘other’) (OR 2.64; 95% CI 1.31–5.33, p  =  0.007) and surgeons practicing in the United States (OR 6.53, 95% CI 2.18–19.52, p  =  0.01 versus Europe) were more likely to recommend continued immobilization. Adoption of shorter immobilization times for CT-confirmed nondisplaced scaphoid waist fractures may be hindered by surgeon attention to fracture tenderness and radiographic appearance.

Information communication technologies are evolving rapidly and have huge impact on everyday life. This does not come without dangers, i.e., it is actively followed by wide range of malicious activities that impact the companies forcing them to protect their information at all costs. Cyber attacks today are usually consisting of multiple carefully planned hardly detectable steps causing severe damage to companies. This paper examines the capability of security information and event management (SIEM) system with applied partial rules in detecting the multi-step attacks. Fine tuning was focused on detecting partial attack patterns that were important and specific to environment and positive results were gained. The results show that when using the partial rule approach in SIEM for incident detection, the number of detected advanced multistage cyber attacks has increased, thereby contributing to the overall security in cyber space.

Cold Atmospheric Plasma (CAP) is an ionized gas near room temperature. Its anti-tumor effect can be transmitted either by direct treatment or mediated by a plasma-treated solution (PTS), such as treated standard cell culture medium, which contains different amino acids, inorganic salts, vitamins and other substances. Despite extensive research, the active components in PTS and its molecular or cellular mechanisms are not yet fully understood. The purpose of this study was the measurement of the reactive species in PTS and their effect on tumor cells using different plasma modes and treatment durations. The PTS analysis yielded mode- and dose-dependent differences in the production of reactive oxygen and nitrogen species (RONS), and in the decomposition and modification of the amino acids Tyrosine (Tyr) and Tryptophan (Trp). The Trp metabolites Formylkynurenine (FKyn) and Kynurenine (Kyn) were produced in PTS with the 4 kHz (oxygen) mode, inducing apoptosis in Mel Im melanoma cells. Nitrated derivatives of Trp and Tyr were formed in the 8 kHz (nitrogen) mode, elevating the p16 mRNA expression and senescence-associated ß-Galactosidase staining. In conclusion, the plasma mode has a strong impact on the composition of the active components in PTS and affects its anti-tumor mechanism. These findings are of decisive importance for the development of plasma devices and the effectiveness of tumor treatment.

Introduction: Active aging is a process of optimizing of opportunities for health, participation, and safety to improve the quality of life as people age. Therapeutic exercises to strengthen muscles are especially important for the elderly, and the results of such exercises are positive in people with functional limitations. The aim of the study was to assess functional mobility of people in the 3rd age of life after programmed therapeutic exercises.Methods: The prospective study included two groups of 130 respondents over the age of 65 who came to the “Centre for Healthy Aging” in Novo Sarajevo in the period from September 1, 2014, until March 1, 2015. Using the time up and go test (TUG), the basic functional mobility was assessed and it represents the minimum time the respondent needs to get up from the armchair, walk a distance of three meters, turn around, and sit back in the armchair. We tested the respondents at the beginning, in the middle, and at the end of the study, which lasted for 6 months.Results: Analysis of the gender structure of the control and the test groups, using the Chi-square test, found a statistically significant difference, and in the test group, there were more female subjects than in the control group, χ2 = 50.620; p = 0.001. Analysis of the functional mobility of the respondents of the test groups using the TUG at the end of the study found that the respondents of the test group needed statistically significantly less time to perform the test (8.84 seconds) compared to the control group (9.59 seconds) and test Group B (9.41 seconds), F = 4.711; p = 0.041.Conclusion: Programmed therapeutic exercise leads to a significant improvement in functional mobility of persons in the 3rd age of life.

Following the idea of sustainability in food production, a yogurt premix based on beetroot (Beta vulgaris) pomace flour (BPF) was developed. BPF was granulated with lactose solution containing lactic acid bacteria (LAB) by a fluidized bed. Particle size increased ~30%. A decrease in Carr Index from 21.5 to 14.98 and Hausner ratio from 1.27 to 1.18 confirmed improved flowability of granulated BPF, whereas a decrease in water activity implied better storability. Yogurts were produced weekly from neat starters and granulated BPF (3% w/w) that were stored for up to one month (4 °C). High viability of Streptococcus thermophilus was observed. Less pronounced syneresis, higher inhibition of colon cancer cell viability (13.0–24.5%), and anti-Escherichia activity were ascribed to BPF yogurts or their supernatants (i.e., extracted whey). Acceptable palatability for humans and dogs was demonstrated. A survey revealed positive consumers’ attitudes toward the granulated BPF as a premix for yogurts amended to humans and dogs. For the first time, BPF granulated with LAB was used as a premix for a fermented beverage. An initial step in the conceptualization of a novel DIY (do it yourself) formula for obtaining a fresh yogurt fortified with natural dietary fiber and antioxidants has been accomplished.

Although functional asymmetry is very common and normal in professional athletes, the better interlimb symmetry between dominant and nondominant sides (bilateral symmetry) could contribute to successful performance in basketball. The aim of this study was to evaluate the importance of bilateral symmetry of the one-leg jumping and agility performances in differentiating basketball players according to their (i) playing position (guards, forwards, and centers) and (ii) performance levels (first division vs. second division). The participants were 102 professional male basketball players, with all members of the teams competing in the two highest national divisions at the moment of testing (height: 194.92 ± 8.09 cm; body mass: 89.33 ± 10.91 kg; 21.58 ± 3.92 years of age). Performance levels (first division, N = 58 vs. second division, N = 44) and playing positions (guards, N = 48; forwards, N = 22; centers, N = 32) were observed as dependent variables. We measured one-leg jumping capacities (running vertical jump and lay-up vertical jump), basketball-specific preplanned agility (CODS), and basketball-specific reactive agility (RAG), all executed on dominant and nondominant sides. Accordingly, the bilateral symmetry of jumping and agility was calculated by calculating the ratio of the corresponding performances on the dominant and nondominant sides. Factorial analysis of variance (performance levels × positions) indicated that the bilateral symmetry of one-leg jumping differentiated players according to their playing position, with better bilateral symmetry among guards (F-test = 6.11 (medium effect size) and 5.81 (small effect size), p < 0.05 for lay-up and running-jump symmetry, respectively). Performance levels significantly differed in the bilateral symmetry of lay-up jump, with better symmetry for first-division players (F-test = 10.11 (medium effect size), p < 0.001), which was mostly influenced by significant differences among guards. Playing positions and performance levels did not differ in bilateral symmetry of the CODS and RAG. The study reveals the importance of bilateral symmetry of the sport-specific performance in differentiating playing positions and performance levels in basketball. Further studies in other multidirectional sports and other sport-specific performances are warranted.