To decode the function and molecular recognition of several recently discovered cytosine derivatives in the human genome – 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine – a detailed understanding of their effects on the structural, chemical, and biophysical properties of DNA is essential. Here, we review recent literature in this area, with particular emphasis on features that have been proposed to enable the specific recognition of modified cytosine bases by DNA-binding proteins. These include electronic factors, modulation of base-pair stability, flexibility, and radical changes (...) in duplex conformation. We explore these proposals and assess whether or not they are supported by current biophysical data. This analysis is focused primarily on the properties of epigenetically modified DNA itself, which provides a basis for discussion of the mechanisms of recognition by different proteins. 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine have recently been discovered in mammalian DNA and appear to have essential regulatory roles. Here, we summarize recent investigations into their effects on the structural, chemical, and biophysical properties of DNA, an understanding of which is essential to decoding their behavior in the genome. (shrink)

Proceedings of the Steklov Institute of Mathematics is a cover-to-cover translation of the Trudy Matematicheskogo Instituta imeni V.A. Steklova of the Russian Academy of Sciences. Each issue ordinarily contains either one book-length article or a collection of articles pertaining to the same topic.

Physicians play a critical role in preventing and treating firearm injury, although the scope of that role remains contentious and lacks systematic definition. This piece aims to utilize the fundamental principles of medical ethics to present a framework for physician involvement in firearm violence. Physicians' agency relationship with their patients creates ethical obligations grounded on three principles of medical ethics — patient autonomy, beneficence, and nonmaleficence. Taken together, they suggest that physicians ought to engage in clinical screening and treatment related (...) to firearm violence. The principle of beneficence also applies more generally, but more weakly, to relations between physicians and society, creating nonobligatory moral ideals. Balanced against physicians' primary obligations to patient agency relationships, general beneficence suggests that physicians may engage in public advocacy to address gun violence, although they are not ethically obligated to do so. A fourth foundational principle — justice — requires that clinicians attempt to ensure that the benefits and burdens of healthcare are distributed fairly. (shrink)

The paper considers the intellectual computer mathematics system InparSolver, which is designed to automatically explore and solve basic classes of computational mathematics problems on multi-core computers with graphics accelerators. The problems of results reliability of solving problems with approximate input data are outlined. The features of the use of existing computer mathematics systems are analyzed, their weaknesses are found. The functionality of InparSolver, some innovative approaches to the implementation of effective solutions to problems in a hybrid architecture are described. Examples (...) of applied usage of InparSolver for processes mathematical modeling in various subject areas are given. Nowadays, new more complex objects and phenomena in many subject areas are constantly emerging, which are subject to mathematical research on a computer. This encourages the development of new numerical methods and technologies of mathematical modeling, as well as the creation of more powerful computers for their implementation. With the advent and constant development of supercomputers of various architectures, the problems of their effective use, expansion of tasks range should be solved, ensuring the reliability of computer results and increasing the level of intellectual information support for users ‒ specialists in various fields. Today, the issues of solving these problems are given special attention by many specialists in the fields of information technology and parallel programming. The world's leadingscientists in the field of computer technology see the solution to the problems of efficient usage of modern supercomputers in algorithmic software creation that easily adapts to different computer architectures with different types of memory and coprocessors, supports efficient parallelism on millions of cores etc. In addition, improving the efficiency of high-performance computing on modern supercomputers is provided by their intellectualization, transferring to the computer to perform a significant part of the functions. The industry of development and usage of intelligent computer technologies is one of the main directions of science and technology development in modern society. (shrink)

Gestational surrogacy relies on a legal agreement between the surrogate and the intended parents to define the roles and responsibilities of the parties, including explicit consent by the surrogate to allow the physician to release all pregnancy-related medical information to the intended parents. In the event of surrogate misconduct, however, physicians may feel conflicted if the surrogate asks the physician to withhold information about potentially dangerous behaviour in pregnancy from the intended parents. While the American Society for Reproductive Medicine guidelines (...) may support disclosure over the objections of the surrogate, the authors argue that such disclosure is a violation of the surrogate’s rights and the physician’s ethical and professional duties. A surrogate’s confidentiality must be maintained as it is an essential element of the physician–patient relationship. (shrink)

Для юристов-практиков и разработчиков законов, студентов, аспирантов и преподавателей юридических вузов и факультетов.

Tri filosofskikh "opravdanii︠a︡" (teodit︠s︡ei︠a︡, antropodit︠s︡ei︠a︡, kosmodit︠s︡ei︠a︡ Serebri︠a︡nogo veka) -- Russkai︠a︡ sofiologii︠a︡ i kabbala -- S. Bulgakov : nauka sofiologii︠a︡ (ili konet︠s︡ religii) -- Tretiĭ Zavet o. Sergii︠a︡ Bulgakova -- Tretʹezavetnai︠a︡ misterii︠a︡ ("malai︠a︡" trilogii︠a︡ Bulgakova).

Precision agriculture is a breakthrough in digital farming technology, which facilitates the application of precise and exact amount of input level of water and fertilizer to the crop at the required time for increasing the yield. Since agriculture relies on direct rainfall than irrigation and the prediction of rainfall date is easily available from web source, the integration of rainfall prediction with precision agriculture helps to regulate the water consumption in farms. In this work, an edge computing model is developed (...) for predicting soil moisture in real time and managing the water usage in accordance with rain prediction. A soil moisture prediction hybrid algorithm has been developed that revolves around the decision-making techniques with live environmental parameters including weather parameters for the prediction of soil moisture through the impact of precipitation. Numerous algorithms with the combination of regression + clustering are estimated, and it is inferred that XGBoost + k-means outperforms other algorithmic combinations that is deployed in edge model. This model is used as an intermediary between the end IoT devices and cloud that results in the saving of computationally intensive processing performed on cloud servers. The servers located on a local edge network perform the developed algorithmic computations. Avoiding transmission over the cloud results in significant latency, response time, and computation power savings and therefore increases the efficiency of data transfer. The proposed edge computing model is implemented in Raspberry Pi as an edge, Heroku as cloud, and edge nodes as the combination of Pi with actuators and sensors. The monitored data from Pi are stored in MongoDB webserver that is controlled by Web dashboard. Finally, the developed model is implemented in cloud and edge where the edge server implementation performs better in terms of latency, bandwidth, throughput, response time, and CPU memory usage. (shrink)

When we hear about a transgression, we may consider whether the perpetrator’s individual circumstances make their transgression more understandable or excusable. Mitigating circumstances may reduce the severity of punishment that is deemed appropriate, both intuitively and legally. But importantly, in courts of public opinion and of law, mitigating information is typically presented only after information about a perpetrator’s transgression. We explore whether this sequence influences the force of mitigating evidence. Specifically, in two studies, we examined whether presenting evidence about a (...) perpetrator’s background before or after evidence of their violation influenced how severely U.S. participants punished perpetrators. In Study 1 (N = 132), evidence about the perpetrator’s mitigating circumstances reduced punishment only when it was presented before evidence about the perpetrator’s violation. Study 2 (N = 316) additionally revealed this moderating effect of presentation order across a variety of premeditated and impulsive violations. These findings are consistent with person-centered theories of punishment and with the Story Model of adjudication. (shrink)

Background: Family members are often required to act as substitute decision-makers when health care or research participation decisions must be made for an incapacitated relative. Yet most families are unable to accurately predict older adult preferences regarding future health care and willingness to engage in research studies. Discussion and documentation of preferences could improve proxies' abilities to decide for their loved ones. This trial assesses the efficacy of an advance planning intervention in improving the accuracy of substitute decision-making and increasing (...) the frequency of documented preferences for health care and research. It also investigates the financial impact on the healthcare system of improving substitute decision-making. Methods/DesignDyads (n = 240) comprising an older adult and his/her self-selected proxy are randomly allocated to the experimental or control group, after stratification for type of designated proxy and self-report of prior documentation of healthcare preferences. At baseline, clinical and research vignettes are used to elicit older adult preferences and assess the ability of their proxy to predict those preferences. Responses are elicited under four health states, ranging from the subject's current health state to severe dementia. For each state, we estimated the public costs of the healthcare services that would typically be provided to a patient under these scenarios. Experimental dyads are visited at home, twice, by a specially trained facilitator who communicates the dyad-specific results of the concordance assessment, helps older adults convey their wishes to their proxies, and offers assistance in completing a guide entitled My Preferences that we designed specifically for that purpose. In between these meetings, experimental dyads attend a group information session about My Preferences. Control dyads attend three monthly workshops aimed at promoting healthy behaviors. Concordance assessments are repeated at the end of the intervention and 6 months later to assess improvement in predictive accuracy and cost savings, if any. Copies of completed guides are made at the time of these assessments. DiscussionThis study will determine whether the tested intervention guides proxies in making decisions that concur with those of older adults, motivates the latter to record their wishes in writing, and yields savings for the healthcare system. Trial RegistrationISRCTN89993391. (shrink)