Chemistry of Spontaneous Alkylation of Methimazole with 1,2-Dichloroethane

Spontaneous S-alkylation of methimazole (1) with 1,2-dichloroethane (DCE) into 1,2-bis[(1-methyl-1H-imidazole-2-yl)thio]ethane (2), that we have described recently, opened the question about its formation pathway(s). Results of the synthetic, NMR spectroscopic, crystallographic and computational studies suggest that, under given conditions, 2 is obtained by direct attack of 1 on the chloroethyl derivative 2-[(chloroethyl)thio]-1-methyl-1H-imidazole (3), rather than through the isolated stable thiiranium ion isomer, i.e., 7-methyl-2H, 3H, 7H-imidazo[2,1-b]thiazol-4-ium chloride (4a, orthorhombic, space group Pnma), or in analogy with similar reactions, through postulated, but unproven intermediatethiiranium ion 5. Furthermore, in the reaction with 1, 4a prefers isomerization to the N-chloroethyl derivative, 1-chloroethyl-2,3-dihydro-3-methyl-1H-imidazole-2-thione (7), rather than alkylation to 2, while 7 further reacts with 1 to form 3-methyl-1-[(1-methyl-imidazole-2-yl)thioethyl]-1H-imidazole-2-thione (8, monoclinic, space group P 21/c). Additionally, during the isomerization of 3, the postulated intermediate thiiranium ion 5 was not detected by chromatographic and spectroscopic methods, nor by trapping with AgBF4. However, trapping resulted in the formation of the silver complex of compound 3, i.e., bis-{2-[(chloroethyl)thio]-1-methyl-1H-imidazole}-silver(I)tetrafluoroborate (6, monoclinic, space group P 21/c), which cyclized upon heating at 80 °C to 7-methyl-2H, 3H, 7H-imidazo[2,1-b]thiazol-4-ium tetrafluoroborate (4b, monoclinic, space group P 21/c). Finally, we observed thermal isomerization of both 2 and 2,3-dihydro-3-methyl-1-[(1-methyl-1H-imidazole-2-yl)thioethyl]-1H-imidazole-2-thione (8), into 1,2-bis(2,3-dihydro-3-methyl-1H-imidazole-2-thione-1-yl)ethane (9), which confirmed their structures.

Cardiac diseases following COVID-19 in children and adults: A narrative review on mechanisms and medical implications

Objectives: In December 2019, SARS-CoV2 outbreak from China resulted in Covid-19 worldwide. The involvement of different organs, especially, heart disease can lead to hospitalization and enhance the rate of mortality and morbidity among severe patients. In a narrative review, we aimed to investigate the involvement of heart in adult and children with COVID-19 in critically ill patients. Methods: The clinical and paraclinical manifestation of diseases in adults and children were searched in standard databases, such as PubMed, Google Scholar, Scopus, est. Also, the possible underlying mechanisms were investigated. Results: The CVDs in COVID-19 patients has been characterized by several abnormalities such as myocarditis, acute myocardial injury, acute coronary syndrome, heart failure, arrhythmias, sudden cardiac arrest, coagulation abnormalities, thrombosis, and Kawasaki disease. The most probable mechanisms are attributed to SARS-CoV2 direct and indirect effects. The presence of angiotensin-converting enzyme 2 (ACE2) was confirmed in the cardiac tissue, confirming the direct attack of virus. Moreover, the cytokine storm as a result of enhanced levels of inflammatory mediators and infiltration of inflammatory cells into the cardiac disease, coagulation abnormalities, and endothelial dysfunction contribute to disease. Conclusion: Cardiac diseases are seen in children and adults with COVID-19, related to the different mechanisms, mainly direct attack of virus and cytokine storm. Increasing the knowledge of cardiologists about the cardiac manifestations of COVID-9 in children and adults and underlying mechanisms can improve the consequences and reduce the mortality and morbidity rate among hospitalized patients.

The Complex Structure of the Pharmacological Drug–Disease Network

The complexity of drug–disease interactions is a process that has been explained in terms of the need for new drugs and the increasing cost of drug development, among other factors. Over the last years, diverse approaches have been explored to understand drug–disease relationships. Here, we construct a bipartite graph in terms of active ingredients and diseases based on thoroughly classified data from a recognized pharmacological website. We find that the connectivities between drugs (outgoing links) and diseases (incoming links) follow approximately a stretched-exponential function with different fitting parameters; for drugs, it is between exponential and power law functions, while for diseases, the behavior is purely exponential. The network projections, onto either drugs or diseases, reveal that the co-ocurrence of drugs (diseases) in common target diseases (drugs) lead to the appearance of connected components, which varies as the threshold number of common target diseases (drugs) is increased. The corresponding projections built from randomized versions of the original bipartite networks are considered to evaluate the differences. The heterogeneity of association at group level between active ingredients and diseases is evaluated in terms of the Shannon entropy and algorithmic complexity, revealing that higher levels of diversity are present for diseases compared to drugs. Finally, the robustness of the original bipartite network is evaluated in terms of most-connected nodes removal (direct attack) and random removal (random failures).

Derivative-free optimization adversarial attacks for graph convolutional networks

In recent years, graph convolutional networks (GCNs) have emerged rapidly due to their excellent performance in graph data processing. However, recent researches show that GCNs are vulnerable to adversarial attacks. An attacker can maliciously modify edges or nodes of the graph to mislead the model’s classification of the target nodes, or even cause a degradation of the model’s overall classification performance. In this paper, we first propose a black-box adversarial attack framework based on derivative-free optimization (DFO) to generate graph adversarial examples without using gradient and apply advanced DFO algorithms conveniently. Second, we implement a direct attack algorithm (DFDA) using the Nevergrad library based on the framework. Additionally, we overcome the problem of large search space by redesigning the perturbation vector using constraint size. Finally, we conducted a series of experiments on different datasets and parameters. The results show that DFDA outperforms Nettack in most cases, and it can achieve an average attack success rate of more than 95% on the Cora dataset when perturbing at most eight edges. This demonstrates that our framework can fully exploit the potential of DFO methods in node classification adversarial attacks.

A Year after - Could we Move beyond Psychosomatics and Dissociation

Living in a global world that is continuously changing while creating the experience of fluidity, we are losing ground and, therefore, stability. It affects mental health across the life span. During the last 12 months from the first WHO notification of the novel coronavirus 2019-nCoV, humanity started to experience a dramatic change in the level of plans, norms, expectations. Besides fear for personal safety and health, the directed distancing increased the gap in everyday quality of possibilities for personal contacts and support. Losing the ground and experience trembling, we were inevitably facing blurred boundaries, insecurity and a direct attack on our will and who we are. Furthermore, a year after, we realize that we are in the fertile ground for the manifestation and experience of anxiety, panic, and numerous psychosomatic disorders. The whole of humanity is suffering. Hence, those coming from helping professions (psychologist, psychotherapists, social workers) dealing with mental health are experiencing the kick even harder. The research we are conducting is checking their wellbeing a year after.

India’s Other Religious Freedom Problems

There is no doubt that India is far from perfect when it comes to religious freedom. Indeed, India’s religious freedom problems have become an increasing focus of scholarly and policy attention. However, almost all of this attention is directed at one particular subset of religious freedom problems—i.e., restrictions imposed on the religious freedom of India’s minority communities, and particularly Muslims and Christians. Meanwhile, serious religious freedom challenges experienced by members of India’s Hindu majority population tend to be ignored. In this article: (1) I first describe the religious freedom situation in India as a complex terrain that requires a multi-dimensional mapping. (2) I then survey existing, influential studies of the religious freedom situation in India and identify their tendency to generate flat, one-dimensional mappings, and their consequent failure to analyze restrictions on the religious freedom of India’s Hindus, including both Hindu individuals and institutions. (3) I briefly analyze India’s regime of “Hindu Erastianism”—i.e., its extensive system of state regulation and control of Hindu institutions—and suggest how and why this regime amounts to a direct attack on core features of institutional religious freedom. (4) I conclude by briefly suggesting that the whole range of India’s religious freedom problems—including its “other”, less discussed problems—can be traced to a longstanding and destructive pattern of ideological polarization that owes as much to an uncompromising statist secularism as to Hindu nationalism. The existence of this now deeply ingrained pattern bodes ill for improvements in India’s religious freedom situation in the short term, and suggests that it is the country’s public culture, rather than its political balance of power, that must change if the world’s largest democracy is to enjoy greater religious freedom and tolerance in the future.

Direct Participation in Hostilities and Its Effect on Proportionality

Unlike members of the armed forces and combatants who can be targeted, civilians are protected from direct attack. However, civilians do not always enjoy protection. When civilians take a direct part in the hostilities, such as by taking up arms against the enemy, they lose their civilian protection and can be lawfully targeted. Classifying a civilian who is directly participating in hostilities as such is relevant to proportionality as well as to the principle of distinction, as it changes the proportionality analysis in two complementary ways. First, an attack on a civilian that is taking a direct part in hostilities would arguably augment the expected military advantage of the strike. Second, such civilians do not enjoy protection from attack and are also not considered civilians in the proportionality assessment. This means that classifying civilians as direct participants in hostilities might make an otherwise disproportionate attack proportionate, and vice versa. This chapter explains the concept of direct participation in hostilities, and its relevance to the proportionality analysis.

Analysis and Implementation of Honeyd as a Low-Interaction Honeypot in Enhancing Security Systems

Every computer connected to a wide computer network is vulnerable to the occurrence of data, information, resources and services that exist in the system from actions such as intrusion, wiretapping, theft and misuse of important data to damage to network systems, which are carried out by irresponsible intruders, wiretapping, theft and misuse of important data by individuals, groups, within a company/government agency or private sector, even damage to computer network systems may occur. in a company, which is done by an intruder or attacker who is not responsible. Honeypot honeyd is a method that can be applied, implemented in medium to large scale companies, especially those that have implemented computer-based systems and technology, to prevent, anticipate bad actions before they occur and take quick action when bad impacts occur. Honeypot honeyd with low-interaction, which is to interact indirectly with the attacker, because honeyd positions itself as a bait or a shadow server that is deliberately attacked so that the results of the attack can be known and analyzed. In this research, honeyd honeypot is a shadow server that resembles a real server, which has several services along with ports that are deliberately opened for attack. The results of this research can be seen that there is an infiltration or direct attack, seen from the increase in network traffic above normal on the monitor system, and also can be seen log files from Honeyd in detail what the attackers have done or are currently doing to be analyzed and then take precautions, anticipation, socialization of security in carrying out activities that are directly related to the outside world through the network, improving both servers, network systems and existing services. Thus the honeyd honeypot can help save important data, resources and can improve computer network security systems.

Mission and reception of St Justin Popović

This review essay brings a closer look at two books about Serbian saint and theologian Justin Popović, both were published in 2019 in Serbian. The first one, presented and analysed in this review, is the international thematic conference proceedings Mission and thought of St Justin Popović, edited by Vladimir Cvetković and Bogdan Lubardić from the Orthodox Theological Faculty in Belgrade (Serbia). The second one, presented in the next review, is Justin of Ćelije and England: Ways of Reception of British Theology, Literature and Science, written by Bogdan Lubardić. There is no need to introduce the life and work of Justin Popović (1894–1979) to the readers of this journal as it is generally known: monk and saint of the Orthodox Church (St Justin the New of Ćelije), professor at the University of Belgrade, co-founder of the Serbian Philosophical Society, one of the most prominent and important Orthodox theologians of the twentieth century. In my modest opinion, these two books open a new chapter in the research of Justin Popović’s legacy, in contrast to revival-apologetic and descriptive approach that previously dominated the reception of Justin Popović’s thoughts. This new approach is characterized by a non-ideological approach to Justin’s work and balances between two extremes, in a certain sense it proposes a middle path. The first extreme, pietistic and defensive-panegyric, considers any criticism of Justin’s work to be a direct attack on his holiness. The second extreme finds in Justin’s work a justification to reject the Serbian Church and all Orthodoxy due to their anti-modern and retrograde nature. Both extremes had fed each other for years and insist on the objectivity and complete truthfulness of their own interpretation of Justin’s work. The proposed middle ground no longer has as the starting point of whether Justin’s views are correct or not, but it considers the reasons and circumstances in which Justin’s work occurs.