Here we review concepts related to an ensemble description of G-protein-coupled receptors. The ensemble is characterized by both inactive and active states, whose equilibrium populations and exchange rates depend sensitively on ligand, environment, and allosteric factors. This review focuses on the adenosine A2 receptor, a prototypical class A GPCR. 19F Nuclear Magnetic Resonance studies show that apo A2AR is characterized by a broad ensemble of conformers, spanning inactive to active states, and resembling states defined earlier for rhodopsin. In keeping with (...) ideas associated with a conformational selection mechanism, addition of agonist serves to allosterically restrict the overall degrees of freedom at the G protein binding interface and bias both states and functional dynamics to facilitate G protein binding and subsequent activation. While the ligand does not necessarily “induce” activation, it does bias sampling of states, increase the cooperativity of the activation process and thus, the lifetimes of functional activation intermediates, while restricting conformational dynamics to that needed for activation. GPCRs represent a ubiquitous class of transmembrane receptors, responsible for cell signaling and cell homeostasis. Their activation gives rise to conformational changes that allow the receptor to engage downstream partners. Activation can be thought of in terms of a free energy landscape associated with distinct conformers, responsible for the process. Here, the action of ligands is seen to alter this landscape by enabling transitions between key intermediates. (shrink)

that Buddhism is best understood as a philosophy of practice-or a.

As the world keeps advancing, the need for automated interconnected devices has started to gain significance; to cater to the condition, a new concept Internet of Things has been introduced that revolves around smart devicesʼ conception. These smart devices using IoT can communicate with each other through a network to attain particular objectives, i.e., automation and intelligent decision making. IoT has enabled the users to divide their household burden with machines as these complex machines look after the environment variables and (...) control their behavior accordingly. As evident, these machines use sensors to collect vital information, which is then the complexity analyzed at a computational node that then smartly controls these devicesʼ operational behaviors. Deep learning-based guessing attack protection algorithms have been enhancing IoT security; however, it still has a critical challenge for the complex industries’ IoT networks. One of the crucial aspects of such systems is the need to have a significant training time for processing a large dataset from the networkʼs previous flow of data. Traditional deep learning approaches include decision trees, logistic regression, and support vector machines. However, it is essential to note that this convenience comes with a price that involves security vulnerabilities as IoT networks are prone to be interfered with by hackers who can access the sensor/communication data and later utilize it for malicious purposes. This paper presents the experimental study of cryptographic algorithms to classify the types of encryption algorithms into the asymmetric and asymmetric encryption algorithm. It presents a deep analysis of AES, DES, 3DES, RSA, and Blowfish based on timing complexity, size, encryption, and decryption performances. It has been assessed in terms of the guessing attack in real-time deep learning complex IoT applications. The assessment has been done using the simulation approach and it has been tested the speed of encryption and decryption of the selected encryption algorithms. For each encryption and decryption, the tests executed the same encryption using the same plaintext for five separate times, and the average time is compared. The key size used for each encryption algorithm is the maximum bytes the cipher can allow. To the comparison, the average time required to compute the algorithm by the three devices is used. For the experimental test, a set of plaintexts is used in the simulation—password-sized text and paragraph-sized text—that achieves target fair results compared to the existing algorithms in real-time deep learning networks for IoT applications. (shrink)

Pandey, V. Introduction.--Kalelkar, K. S. Jainism, a familyhood of all religions.--David, M. D. From Risabha to Mahavira.--Chalil, J. E. Glimpses of Southern Jainism.--Gopani, A. S. Life and culture in Jaina narrative literature, 8th, 9th and 10th century A.D.--Gopani, A. S. Position of women in Jaina literature.--Ranka, R. Evolution of Jaina thought.--Pandey, V. Jaina philosophy and religion.--Shah, C. C. Jainism and modern life.--Sankalia, H. D. The great renunciation.--Shah, U. P. Jaina contribution to Indian art.--Gorakshkar, S. Early metal images of (...) the Jainas.--Bhagwati, U. Bibliographical aids for the study of Jainism. (shrink)

Among psychologists and vision scientists,binocular rivalry has enjoyed sustainedinterest for decades dating back to the 19thcentury. In recent years, however, rivalry''saudience has expanded to includeneuroscientists who envision rivalry as a tool for exploring the neural concomitants ofconscious visual awareness and perceptualorganization. For rivalry''s potential to berealized, workers using this tool need toknow details of this fascinating phenomenon,and providing those details is the purpose ofthis article. After placing rivalry in ahistorical context, I summarize major findingsconcerning the spatial characteristics and thetemporal dynamics (...) of rivalry, discuss two majortheoretical accounts of rivalry ( eye vs stimulus rivalry) and speculate on possibleneural concomitants of binocular rivalry. (shrink)

The high precision attained by cosmological data in the last few years has increased the interest in exact solutions. Analytic expressions for solutions in the Standard Model are presented here for all combinations of Λ = 0, Λ ≠ 0, κ = 0, and κ ≠ 0, in the presence and absence of radiation and nonrelativistic matter. The most complete case (here called the ΛγCDM Model) has Λ ≠ 0, κ ≠ 0, and supposes the presence of radiation and dust. (...) It exhibits clearly the recent onset of acceleration. The treatment includes particular models of interest such as the ΛCDM Model (which includes the cosmological constant plus cold dark matter as source constituents). (shrink)

BLWith new text and full apparatus criticus The Eudemian Ethics was one of two ethical treatises which Aristotle wrote on the subject of ethica or `matters to do with character'. Although the two works cover much the same ground, the Nicomachean Ethics is better known; the poor manuscript tradition of the Eudemian Ethics has made correct translation and interpretation of the text extremely difficult. The subject of the work is the choice of a certain means of conduct, made by a (...) `man of practical wisdom', between two extremes of behaviour: asceticism and yielding to uncontrolled impulses. Aristotle also stresses the notion of moral intention and the importance of virtue of character. This new Oxford Classical Text of the Eudemian Ethics is the result of many years of work. After Sir David Ross's death, his original text was substantially reworked and revised by his friend and colleague R. R. Walzer, who was aided in the revision by his former pupil Mrs Jean Mingay, who continued his work after his death in 1974. Mrs Mingay was fortunate in being able to make use of previously unpublished contributions from D. J. Allan after his death in the late seventies, and more recently has been helped in her work by the suggestions of Professor D. A. Russell, David Robinson, and Christopher Rowe. (shrink)

Sexual reproduction is a composite, not a singular, phenomenon and as such can be subdivided into a number of componentsi.e. fusion, recombination, fission, and the male-female phenomenon. These components can evolve independently, though any evolutionary change in one component is likely to influence the future evolution of the other components. The ambiguity that surrounds the term ‘sex’ due to a failure to recognise the composite nature of sexual reproduction has led to considerable confusion in past discussions of the evolution of (...) the phenomenon. This paper considers the possible chronological interaction of the components of sexual reproduction both with each other and with the sequence of selective pressures that seem likely to have acted. This chronological approach is used to consider: the origin of sexual reproduction; the evolution of sexual reproduction in the common ancestor of the procaryotes and eucaryotes; the modification of the ancestral system in the procaryote line following the procaryote-eucaryote dichotomy; and the modification of the ancestral system in the eucaryote line up to the origin of the male-female phenomenon.It is suggested that the fusion and recombination of the first living organisms were chronological continuations of the fusion and recombination of complex organic molecules that led up to the origin of life. The evolution of the third major component of sexual reproductioni.e. fission , by definition coincided with the origin of life. Initial selection on the components of sexual reproduction are likely to have been related to the optimum manifestations of size, complexity, diversity, multiplication, and distribution. Resultant early evolutionary trends are likely to have been: selective fusion between more-similar organisms; increase in number of fissions per fusion; and less recombination.The procaryote-eucaryote dichotomy is argued to have evolved in response to the increasing cellular problems of packing and replicating an increasing amount of hereditary material. The evolution of a single circular hereditary organelle in the procaryote line is argued to have led to the loss of total fusion and the specialisation of individuals into either donors or recipients. The donor-recipient phenomenon of procaryotes is directly analogous to the male-female phenomenon of eucaryotes and leads to parallel evolution due to sexual selection in both groups. In the eucaryote line the ancestral mechanism of sexual reproduction is argued to have persisted through, but to have been greatly modified by, the evolution of complex machinery for the handling of multiple hereditary organelles at cell division and reduction division. The evolutionary modification of the ancestral system of sexual reproduction is suggested to have led in eucaryotes to the evolution of: the species phenomenon; allelic recombination; and the male-female phenomenon. (shrink)

The third international conference on classical influences took place in Cambridge in 1977 under the title 'Classical Influences in Western Education, Philosophy and Social Theory'. Dr Bolgar has here collected and edited the proceedings and produced a volume which attempts to relate the progress of classical studies to the general history of ideas from the mid-seventeenth to the mid-nineteenth century. The book should be of interest to specialists in classical studies, to students of the literature of the period, and to (...) students of eighteenth-century French, Italian and American history. (shrink)

Almost all ethical guidelines and legislative policies concerning biomedical research involving human subjects contain provisions about relevance of research for the participating populations, informed consent, adequate care for research induced injuries and several other safeguards but the poor continue to suffer. Globalization has further aggravated poor people’s vulnerability by exposing them to international markets. Since the developing countries are abode of higher population of the poor they have become the unholy mines of this human ore for researchers. In this paper (...) I examine various dimensions of poverty and analyze the international ethical responses in the area of biomedical research involving human subjects in order to determine their adequacy to protect the poor against exploitation and misuse and conclude that in view of the poor’s inherent and extreme vulnerability and the failure of ethical pronouncements to protect them from misuse and exploitation, they should be excluded from being enrolled as research subjects. (shrink)

This invaluable resource is the first one-volume, in-depth, comprehensive history of modern science ever published.

Розкрито сутність поняття «рейтинг». Доведено значущість рейтингової оцінки для суб’єктів фінансового ринку, зокрема для страхових компаній, потенційних страхувальників, інвесторів та кредиторів.

Despite stringent and fine tuned laws most jurisdictions are not able to curb organ trafficking. Nor are they able to provide organs to the needy. There are reports of the kidnapping and murder of children and adults to “harvest” their organs. Millions of people are suffering, not because the organs are not available but because “morality” does not allow them to have access to the organs. Arguments against organ sale are grounded in two broad considerations: sale is contrary to human (...) dignity, and sale violates equity. Both these objections are examined in this article and it is concluded that they reflect a state of moral paternalism rather than pragmatism. It is argued that a live human body constitutes a vital source of supply of organs and tissues and that the possibilities of its optimum utilisation should be explored. Commercialisation should be curbed not by depriving a needy person of his genuine requirements but by making the enforcement agencies efficient. (shrink)

What is xenophobia? Why is xenophobia immoral? How is xenophobia's conceptual and moral meaning diminished? Investigations of these questions would invigorate xenophobia as a topic in public morality and discourage the public's acquiescing to xenophobia's new prominence. This paper focuses on the third question, the diminishment of xenophobia. In the first section, I outline a general conception of xenophobia. In the second, I explain how theories of membership in liberal democratic societies relegate xenophobia to a minor moral concern. And, in (...) the third, that the conflation of xenophobia with racism disadvantages the former. How liberal Democratic nations imagine membership and how those nations imagine racism shelters xenophobia. (shrink)