Growing evidence suggests that pathological overactivation of the endocannabinoid system (ECS) is associated with dyslipidemia, obesity and diabetes. Indeed, this signalling system acting through cannabinoid receptors has been shown to function both centrally and peripherally to regulate feeding behaviour as well as energy expenditure and metabolism. Consequently, modulation of these receptors can promote significant alterations in body weight and associated metabolic profile. Importantly, blocking cannabinoid receptor type 1 function has been found to prevent obesity and metabolic dysfunction in various murine (...) models and in humans. Here we provide a detailed account of the known physiological role of the ECS in energy balance, and explore how recent studies have delivered novel insights into the potential targeting of this system as a therapeutic means for treating obesity and related metabolic disorders. (shrink)

With special reference to Punjab, India; a study.

Langerhans cells (LCs), residing in the epidermis, are able to induce potent immunogenic responses and also to mediate immune tolerance. We propose that tolerogenic and immunogenic responses of LCs are directed by signaling from the epidermis and involve counter‐acting gene circuits that are coupled to a core maturation gene module. We base our analysis on recent genetic and genomic findings facilitating the understanding of the molecular mechanisms controlling these divergent immune functions. Comparing gene regulatory network (GRN) analyses of various types (...) of dendritic cells (DCs) including LCs we integrate signaling‐dependent (TGFβ, EpCAM, β‐Catenin) and transcription factor (IRF4, IRF1, NFκB) regulated gene circuits that appear to orchestrate the distinctive LC functional states. Our model proposes, that while epidermal signaling in the steady‐state promotes LC tolerogenic function, the disruption of cell‐cell contacts coupled with inflammatory signaling induces LC immunogenic programing. The conceptual framework emphasizes the sensing of discrete epidermal and inflammatory cues by resident LCs in dictating their genomic programing and cell state dynamics. (shrink)

Ocherk 1. Voprosy ontologii -- Ocherk 2. Voprosy ėtiki i ėstetiki -- Ocherk 3. Voprosy gnoseologii i aksiologii.

Prologue, invitation to thinking about God In the Hebrew Bible? -- Part I, questions about God? -- Why does God in the Bible have a body? -- What do God's body parts in the Bible mean? -- Why is God angry in the Bible? -- Does God in the Bible have gender or sexuality? -- Part II, questions about God in the world? -- What can creation tell us about God? -- Who-or what-is the Satan? -- Why do people suffer (...) according to the Hebrew Bible? -- Epilogue, God in the Bible and beyond. (shrink)

Many books explain what is known about the universe. This book investigates what cannot be known. Rather than exploring the amazing facts that science, mathematics, and reason have revealed to us, this work studies what science, mathematics, and reason tell us cannot be revealed. In The Outer Limits of Reason, Noson Yanofsky considers what cannot be predicted, described, or known, and what will never be understood. He discusses the limitations of computers, physics, logic, and our own thought processes. Yanofsky describes (...) simple tasks that would take computers trillions of centuries to complete and other problems that computers can never solve; perfectly formed English sentences that make no sense; different levels of infinity; the bizarre world of the quantum; the relevance of relativity theory; the causes of chaos theory; math problems that cannot be solved by normal means; and statements that are true but cannot be proven. He explains the limitations of our intuitions about the world -- our ideas about space, time, and motion, and the complex relationship between the knower and the known. Moving from the concrete to the abstract, from problems of everyday language to straightforward philosophical questions to the formalities of physics and mathematics, Yanofsky demonstrates a myriad of unsolvable problems and paradoxes. Exploring the various limitations of our knowledge, he shows that many of these limitations have a similar pattern and that by investigating these patterns, we can better understand the structure and limitations of reason itself. Yanofsky even attempts to look beyond the borders of reason to see what, if anything, is out there. (shrink)

Study of Hans-Georg Gadamer's and Julius Stenzel's interpretations of Plato.

In 2018, the Chinese scientist He Jiankui presented his research at the Second International Summit on Human Genome Editing in Hong Kong. While it was intended that he facilitate a workshop, he was instead called on to present his research in heritable human genome editing, where he made the announcement that he had taken great strides in advancement of his research, to the extent that he had gene-edited human embryos and that this had resulted in the live births of two (...) children. While his research ethic and methodology was interrogated, he insisted that two children, twin girls, had been born healthy and that there was another pregnancy (at the time) where birth of a third gene edited child would be imminent. This announcement generated a ripple effect in the scientific community and exposed the gaps in regulation and absence of law relating to the technology. This resulted in a flurry of activity and conversation around regulation of the technology, which scientists stated was not ready for human trials. This article reviews the Third Summit which was held in London in March 2023 and comments on the latest developments in the regulation of heritable human genome editing. (shrink)

The phenomenon of ambivalence is an important one for any philosophy of action. Despite this importance, there is a lack of a fully satisfactory analysis of the phenomenon. Although many contemporary philosophers recognize the phenomenon, and address topics related to it, only Harry Frankfurt has given the phenomenon full treatment in the context of action theory - providing an analysis of how it relates to the structure and freedom of the will. In this paper, I develop objections to Frankfurt's account, (...) all revolving around the charge that his account contains a serious ambiguity between willing and identifying. With such objections in place, I then develop an analysis that avoids the difficulties and ambiguities that Frankfurt's analysis is prey to. I briefly distinguish ambivalence from other types of internal conflict. This paper aims to offer conceptual clarification on the phenomenon of ambivalence, which will then allow for discussions about the normative merits and demerits of ambivalence, the effects of ambivalence on autonomous action, and methods of resolution of ambivalence. (shrink)

Study of Tārkikarakṣā of Varadarāja Miśra, 11th cent., work on Nyaya and Vaiśeṣika philosophy.

The first major work in the history of philosophy to bear the title "Metaphysics" was the treatise by Aristotle that we have come to know by that name. But Aristotle himself did not use that title or even describe his field of study as 'metaphysics'; the name was evidently coined by the first century C.E. editor who assembled the treatise we know as Aristotle's Metaphysics out of various smaller selections of Aristotle's works. The title 'metaphysics' -- literally, 'after the Physics' (...) -- very likely indicated the place the topics discussed therein were intended to occupy in the philosophical curriculum. They were to be studied after the treatises dealing with nature (ta phusika). In this entry, we discuss the ideas that are developed in Aristotle's treatise. (shrink)

Richard Janko's acclaimed translation of Aristotle's _Poetics_ is accompanied by the most comprehensive commentary available in English that does not presume knowledge of the original Greek. Two other unique features are Janko's translations with notes of both the _Tractatus Coislinianus_, which is argued to be a summary of the lost second book of the Poetics, and fragments of Aristotle’s dialogue On Poets, including recently discovered texts about catharsis, which appear in English for the first time.

Walter Glannon argues that our proposal for routine recovery of transplantable cadaveric organs is unacceptable After carefully reviewing his counterarguments, we conclude that, although some of them have merit, none are sufficiently strong to warrant abandoning this plan. Below we respond to each of Glannon's concerns.

Marshall and colleagues (2024) contribute to the literature on autonomy and decision-making capacity by focusing on the case of individuals with opioid use disorder who refuse to remain in the hosp...

"Sir Hermann Bondi, NatureThe late S. Chandrasekhar was best known for his discovery of the upper limit to the mass of a white dwarf star, for which he received ...

Smysl zhizni -- Statʹi raznykh let : Staryĭ i novyĭ nat︠s︡ionalʹnyĭ messianizm. Umozrenie v kraskakh. Dva mira v drevnerusskoĭ ikonopisi. "Inoe t︠s︡arstvo" i ego iskateli v russkoĭ narodnoĭ skazke.

Many religious people are alarmed about features of the current age - violence in the media, a pervasive hedonism, a marginalization of religion, and widespread abortion. These concerns influence politics, but just as there should be a separation between church and state, so should there be a balance between religious commitments and secular arguments calling for social reforms. Robert Audi offers a principle of secular rationale, which does not exclude religious grounds for action but which rules out restricting freedom except (...) on grounds that any rational citizen would accept. The book describes the essential commitments of free democracy, explains how religious and secular moral considerations can be integrated to facilitate co-operation in a world of religious pluralism, and proposes ideals of civic virtue that express the mutual respect on which democracy depends. Audi offers a balanced and sophisticated treatment of the relations between religion and politics in a modern, secular society. (shrink)