In “Missing the Forest for the Trees: Aduhelm, Accelerated Approvals & the Agency,” Dr. Matthew Herder argues that agency capture and politicized discretion drive delays in confirmatory trials of accelerated approval drugs amongst other concerns at US Food and Drug Administration (FDA). In highlighting this important problem and offering nuanced insight into agency workings based in part on interviews with twenty-three unnamed FDA officials and a three-drug case study, Dr. Herder suggests two innovative solutions. However, amidst broader debates balancing agency (...) expertise, data, and delegation, these proposed policy solutions would benefit from more corroborative evidence and consideration of institutional advantages within constitutional limits. (shrink)

The presence of vegetation on railway tracks threatens track safety and longevity. However, vegetation inspections in Sweden are currently being carried out manually. Manually inspecting vegetation is very slow and time consuming. Maintaining an even quality standard is also very difficult. A machine vision-based approach is therefore proposed to emulate the visual abilities of the human inspector. Work aimed at detecting vegetation on railway tracks has been split into two main phases. The first phase is aimed at detecting vegetation on (...) the tracks using appropriate image analysis techniques. The second phase is aimed at detecting the rails in the image to determine the cover of vegetation that is present between the rails as opposed to vegetation present outside the rails. Results achieved in the current work indicate that the machine vision approach has performed reasonably well in detecting the presence/absence of vegetation on railway tracks when compared with a human operator. (shrink)

The Book Studies The Different Aspects Of Tantrism, Its Vastness And Intricacies, Its Heterogeneous And Contradictory Elements And Gives A Historical Perspective To The Conglomeration Of Ideas And Practices Through Space And Time. It Also Incorporates A Review Of Tantric Art And A Glossary Of Technical Terms.

Description: Jain Philosophy : Historical Outline interprets the fundamentals of Jain philosophy from the viewpoint of their historical genesis and development and shows that the incipient stage of the Jain thought-complex agreed totally with the pythagorean approach to philosophy which was based on observed realities and was quite in harmony with the existing socio-political conditions of the time of Lord Mahavira while the sophisticated stage marked by the a priori doctrines and dogmas it had generated in course of its development (...) and by the traditionally floating ideas in regard to the belief in a eternal moral order in the universe, the law of karma, ignorance as the cause of bondage and knowledge as that of liberation, the efficacy of meditation, and so forth, was a persistent juxtaposition in the evolutionary stages of the former. Since no system of Indian philosophy allows a purely isolated treatment, a comparative study of all the philosophical systems has been made here to determine the real nature of the Jain standpoint with more emphasis on the original dynamism of Jainism which had contributed to the growth of various natural sciences, including those of biology and astronomy, on the total rejection of the concept of a supernatural agent in the form of God, on the theories of valid knowledge and on the unique logical system based on the principles of relativity. Contents Preface of the Second Edition Preface of the First Edition Chap. I : INTRODUCTION : 1. The Jains as they are 2. Researches on Jainism 3. Literary Sources 4. Archaeological Sources : Architecture and Sculpture 5. Archaeological Sources : The Epigraphs 6. Parsva and Mahavira 7. Ecclesiastical History Chap. II : THE INCIPIENT STAGE : 1. The Prehistory of Jainism 2. The Historical Background 3. Material Basis of the Great Intellectual Movement 4. The Conflicts in the History of Indian thought 5. Contemporary Philosophical Schools 6. Purana Kassapa 7. Pakudha Kaccayana 8. Makkhali Gosala 9. Sanjaya Belatthiputta 10. Ajita Kesakambalin 11. Social Experiences of Mahavira 12. The Social Basis of Jain Ethics Chap. III : THE SOPHISTICATED STAGE : 1. Jainism and Indian Philosophical Tradition 2. Jain Atheism 3. Jain Logic 4. Scientific Enquiries : Cosmology 5. Scientific Enquiries : Classification of Jiva 6. Scientific Enquiries : Biology, Physiology, Etc 7. Scientific Enquiries : Diseases and Medicines 8. Scientific Enquiries : Astronomy 9. Scientific Enquiries : Atomism 10. Jain Cosmography 11. The Unfounded Speculations and their Ethical Considerations 12. The Nine Fundamentals and the Doctrine of Karma 13. Classification of Karma and the Gunasthanas 14. A Review of the Jain Metaphysics 15. Theory of Knowledge 16. Psychological Ingredients 17. The Non-Absolutist Standpoint Chap. IV : A COMPARATIVE STUDY : 1. Jainism and Vedic Tradition 2. Jainism and Buddhism 3. Jainism and Ajivikism 4. Jainism and Materialism 5. Jainism and Samkhya 6. Jainism and Yoga 7. Jainism and Mimamsa 8. Jainism and Nyaya-Vaisesika 9. Jainism and Vedanta 10. A Subjectwise Comparative Study of the Systems. (shrink)

Study of four works of Sri Krishna Prem, 1898-1965, a Vaishnavite teacher; includes a bibliographical sketch.

Spatially and temporally restricted expression of Hox genes requires multiple mechanisms at both the transcriptional and the post-transcriptional levels. New insight into this precise expression mechanism comes from recent findings of a novel sense–antisense miRNA combination from the bithorax complex of Drosophila melanogaster.1-4 These two miRNAs encoded from the same locus target 3′ untranslated regions of anterior hox genes, Antp, Ubx and abd-A to establish the dominance of posterior hox gene Abd-B in its expression domain. Such double-edge tools, sense–antisense miRNA (...) combinations, also operate at multiple loci in the genome implicating their wider impact on the post-transcriptional gene regulation in eukaryotes. BioEssays 30:1058–1061, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:NEWMAN'S PSYCHOLOGICAL DISCOVERY: THE ILLATIVE SENSE (V. Continued) 15. The Universals. A long and vehement dispute once raged about the reality of universals. Are they only mental creations, forged by the human brain, without any reality outside them, or have they some independent existence apart from their mental reality? Anyhow, there was an apparent contradiction between die universal character of our ideas and the individual character of concrete things. (...) The Scholastics solved this problem by drawing clear distinctions. An idea is an abstraction; as soon as it becomes applicable to a number of objects or things in the same sense, it is a universal idea. The "direct universal" (universale directum seu metaphysicum) as such has no existence apart from our minds, because an existing thing is always bound up with concrete, determining, individualizing notes, and it is these very circumstances or accidents which are ignored by the mind as it strips the thing of its individual characteristics. When the mind reflects on this "direct universal," i.e., on the abstract essence of the thing, it sees that this is to be found in many more things and that it is identical in all those things, and in this way the "reflex or logical universal" is formed (universale reflexum seu logicum). This same essence or quiddity is not really different from the thing itself, but the mind makes abstraction of all accidents, and this foundation makes it possible to apply this idea in die same sense to all other beings of the same kind, whether they are actually existing or not. In other words the universal as a universal has only reality in the mind but it has a foundation or a ground in the thing itself. Newman was not so well acquainted with Scholasticism that he knew and mastered the solution of the problem. As a matter of fact he approached it from quite another angle. Hence when scholastically trained minds read some of his statements on universals, they may feel shocked. They sound very curious, they seem incon418 DR. ZENO, O.F.M. CAP.419 sistent with each other, they apparenüy imply a negation of the objective reality of universals. This makes it necessary to compare the texts and to explain his meaning. a. Newman Inconsistent. We should never lose sight of the fact that Newman had no intention at all to enter the province of philosophy in the restricted sense of the word. "I am only contemplating the mind as it moves in fact, by whatever hidden mechanism,"1 that is what could be put as a heading to every page of the Grammar of Assent. And when he virtually deals with metaphysics, he wants us to consider his statements as hypotheses, or as propositions stated only by the way, and in this department he always wishes "to speak under correction." This explains how he could refer to the universale metaphy sicum and the universale directum in a very correct way without realizing he was teaching Scholastic doctrine. As far as I know, it is Professor Walgrave who has first drawn attention to this fact,2 when he dealt with Newman's alleged conceptualism. Newman states that "even one act of cruelty, ingratitude, generosity or justice reveals to us at once intensive the immutable distinction between those qualities and their contraries; that is, in that particular instance and pro bac vice."3 The same holds for the opposites: right and wrong, true and false, just and unjust, beautiful and deformed.4 In one experience, therefore, he sees a thing as an immutable, absolute quiddity, which objectively and in the same sense belongs to all possible things of the same kind, although the mind does not yet explicidy confirm this universal applicability. The contemplated quality remains limited to the particular case; but in its absoluteness it is stripped of all individual, changeable and concrete characteristics. This is the metaphysical universal of the Scholastics. But Newman also mentions the logical universal when he says: "As we form our notion of whiteness from the actual sight of snow, a lily or a cloud, so, after experiencing the sentiment of approbation which arises in us on the sight of certain... (shrink)

. Speaker recognition has been an active research area for many years. Methods to represent and quantify information embedded in speech signal are termed as features of the signal. The features are obtained, modeled and stored for further reference when the system is to be tested. Decision whether to accept or reject speakers are taken based on parameters of the data modeling techniques. Real world offers various degradations to the signal that hamper the signal quality. The degradations may be due (...) to ambient background noise, reverberation or multispeaker scenario. This paper presents a survey of various feature extraction, data modeling methods, metrics that are used to take the decisions and methods that can be used to preprocess the degraded data that have been used to perform the task of speaker recognition. (shrink)

Recording and manipulating neuronal ensemble activity is a key requirement in advanced neuromodulatory and behavior studies. Devices capable of both recording and manipulating neuronal activity brain-computer interfaces should ideally operate un-tethered and allow chronic longitudinal manipulations in the freely moving animal. In this study, we designed a new intracortical BCI feasible of telemetric recording and stimulating local gray and white matter of visual neural circuit after irradiation exposure. To increase the translational reliance, we put forward a Göttingen minipig model. The (...) animal was stereotactically irradiated at the level of the visual cortex upon defining the target by a fused cerebral MRI and CT scan. A fully implantable neural telemetry system consisting of a 64 channel intracortical multielectrode array, a telemetry capsule, and an inductive rechargeable battery was then implanted into the visual cortex to record and manipulate local field potentials, and multi-unit activity. We achieved a 3-month stability of the functionality of the un-tethered BCI in terms of telemetric radio-communication, inductive battery charging, and device biocompatibility for 3 months. Finally, we could reliably record the local signature of sub- and suprathreshold neuronal activity in the visual cortex with high bandwidth without complications. The ability to wireless induction charging combined with the entirely implantable design, the rather high recording bandwidth, and the ability to record and stimulate simultaneously put forward a wireless BCI capable of long-term un-tethered real-time communication for causal preclinical circuit-based closed-loop interventions. (shrink)

Phosphatidylinositol 4,5‐bisphosphate (PI4,5P2) is a key lipid signaling molecule that regulates a vast array of biological activities. PI4,5P2 can act directly as a messenger or can be utilized as a precursor to generate other messengers: inositol trisphosphate, diacylglycerol, or phosphatidylinositol 3,4,5‐trisphosphate. PI4,5P2 interacts with hundreds of different effector proteins. The enormous diversity of PI4,5P2 effector proteins and the spatio‐temporal control of PI4,5P2 generation allow PI4,5P2 signaling to control a broad spectrum of cellular functions. PI4,5P2 is synthesized by phosphatidylinositol phosphate kinases (...) (PIPKs). The array of PIPKs in cells enables their targeting to specific subcellular compartments through interactions with targeting factors that are often PI4,5P2 effectors. These interactions are a mechanism to define spatial and temporal PI4,5P2 synthesis and the specificity of PI4,5P2 signaling. In turn, the regulation of PI4,5P2 effectors at specific cellular compartments has implications for understanding how PI4,5P2 controls cellular processes and its role in diseases. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:NEWMAN'S PSYCHOLOGICAL DISCOVERY: THE ILLATIVE SENSE (Continued) VI THE FACULTIES OF COGNITION AND APPETITION Since the Grammar of Assent gives us a phenorhenological analysis of the art of thinking and often refers to the influence of other faculties in our reasoning processes, it will be very instructive to examine what the author holds about our faculties of cognition and appetition. This will make us better acquainted with the nature (...) of the illative sense. I. THE SENSES 1. The External Senses and their Objects. We had already arrived at the conclusion that Newman rejects the mere subjectivity of our knowledge. When he writes about this matter he explicitly deals with sensation or sensuous cognition. Although he takes exception to the word "immediate perception," 1 we may nevertheless call him an adherent of direct or immediate realism according to Scholastic terminology, because he emphatically excludes the intervention of a reasoning process from sense perception and uses the term "mediate perception" only to express the instrumentality of experience. In this meaning our perception of external objects is mediate or indirect indeed.2 The fact is that as early as 1839 he wrote in his University Sermons: "Of the material we have direct knowledge through the senses"3 and in 1843: "The senses are direct, immediate, and ordinary informants, and act spontaneously without any will or effort on our part."4 On the importance of sense perception for our mental activities he writes in a series of hitherto unpublished notes, entitled Elements of Thought:6 "I grant or I assume that the soul would not think without some external stimulus; that if it were cut off from all communication from the external world, it would pass this life in a sort of torpor... But then, as soon as it is roused, it reflects upon itself, and thereby gains a number of ideas..." 1. See supra V, 14.2. Supra V, 14.3. P. 205. 4.P. 303 ; cf. Gramm., p. 260. 5.See the unpublished Philosophical Papers, note Fcbr. 24, 1859. 40 DR. ZENO, OJM. CAP.41 Apart from the passages already referred to, Newman nowhere enlarges on the doctrine about the senses. He does not speak about the distinctions between sensible objects; he does not explain the difference between sensation and perception, and uses those terms promiscuously.6 There are no statements on the subject which contradict current Scholastic notions, although sometimes his vague terminology may be an occasion for misunderstandings. For instance, some passages in connection with "images" and "impressions," when read apart from the context, would appear to imply that he identifies them with the Scholastic species a sensibili accepta. However, we shall show further on that. Newman means something quite different. He deals with these species and the so-called sensibilia per acci· dens by the way when describing our knowledge of God7 and teaching that we have evidence of the presence of individuals or substances in the phenomena which occur to our senses. We picture those things to ourselves in those phenomena. They are like pictures, he says, but at the same time "they give us no exact measure or character of the unknown things beyond them." "Therefore when we speak of our having a picture of the things which are perceived through the senses, we mean a certain representation, true as far as it goes, but not adequate." 2. The Internal Senses and their Objects. Newman nowhere gives a distinction between external and internal senses, but nevertheless he speaks about those faculties of the mind which by the Scholastics are called the internal senses. These philosophers distinguish a common sense or rather a central sense (sensus communis), which unites the impressions of the external senses into one whole, makes us conscious of the conditions of our body and notifies to us the sensations of our external as well as internal senses; — the imagination or the faculty which preserves and reproduces things perceived; — the sensuous memory, i. e., the power to retain and to reproduce sense images; — and the vis aestimativa or the instinctive faculty, which discovers without any intellectual means, what is good and what is bad for our welfare. 6.It would seem that he generally... (shrink)

The COVID-19 pandemic has resulted in more than 524 million cases and 6 million deaths worldwide. Various drug interventions targeting multiple stages of COVID-19 pathogenesis can significantly reduce infection-related mortality. The current within-host mathematical modeling study addresses the optimal drug regimen and efficacy of combination therapies in the treatment of COVID-19. The drugs/interventions considered include Arbidol, Remdesivir, Interferon and Lopinavir/ritonavir. It is concluded that these drugs, when administered singly or in combination, reduce the number of infected cells and viral load. (...) Four scenarios dealing with the administration of a single drug, two drugs, three drugs and all four are discussed. In all these scenarios, the optimal drug regimen is proposed based on two methods. In the first method, these medical interventions are modeled as control interventions and a corresponding objective function and optimal control problem are formulated. In this framework, the optimal drug regimen is derived. Later, using the comparative effectiveness method, the optimal drug regimen is derived based on the basic reproduction number and viral load. The average number of infected cells and viral load decreased the most when all four drugs were used together. On the other hand, the average number of susceptible cells decreased the most when Arbidol was administered alone. The basic reproduction number and viral load decreased the most when all four interventions were used together, confirming the previously obtained finding of the optimal control problem. The results of this study can help physicians make decisions about the treatment of the life-threatening COVID-19 infection. (shrink)

Serial analysis of gene expression (SAGE) is a powerful technique that can be used for global analysis of gene expression. Its chief advantage over other methods is that it does not require prior knowledge of the genes of interest and provides qualitative and quantitative data of potentially every transcribed sequence in a particular cell or tissue type. This is a technique of expression profiling, which permits simultaneous, comparative and quantitative analysis of gene‐specific, 9‐ to 13‐basepair sequences. These short sequences, called (...) SAGE tags, are linked together for efficient sequencing. The sequencing data are then analyzed to identify each gene expressed in the cell and the levels at which each gene is expressed. The main benefit of SAGE includes the digital output and the identification of novel genes. In this review, we present an outline of the method, various bioinformatics methods for data analysis and general applications of this important technology. BioEssays 26:916–922, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Various domains of life widely recognise the concept of human rights. Regardless of one's spiritual beliefs or background, individuals possess an inherent understanding of their fundamental rights. This knowledge of human rights originates from Allah, who has communicated it through various messengers, including the esteemed Prophet Muhammad ﷺ. This study focuses on examining the religious perspective on basic human rights in order to establish a comprehensive understanding of these rights. There are two revelations: This study employs a linguistic descriptive analysis (...) approach to evaluate the Holy Quran and the guidance of the Prophet. The study primarily focuses on conducting a content analysis and descriptive analysis of case studies and literary insights found in the Holy Quran and the Prophet's ﷺ guidance. The goal is to extract as much content as possible about human rights. The study has identified four major themes defined by the Holy Quran and the Prophet's ﷺ guidance. The study has improved our understanding of key human rights concepts and suggests that future scholars concentrate on assessing other fundamental rights that the two revelations under investigation have illuminated. (shrink)

Psychiatrists assert that mental illness is a physiological brain disorder. The anti-psychiatry movement refutes this on grounds of lack of evidence claiming that mental illness is socially defined. Len Bowers offers a rational, objective and philosophical critique of the theories of mental illness as a social construct and concludes that, though sometimes misguided, they cannot be wholly rejected. This critical scrutiny of a controversial and keenly-debated issue will be of interest to psychologists, social workers, psychiatrists, sociologists and professionals in paramedical (...) disciplines. (shrink)

_The Contradictions of Modern Moral Philosophy_ is a highly original and radical critique of contemporary moral theory. Paul Johnston demonstrates that much recent moral philosophy is confused about the fundamental issue of whether there are correct moral judgements. He shows that the standard modern approaches to ethics cannot justify - or even make much sense of - traditional moral beliefs. Applied rigorously, these approaches suggest that we should reject ethics as a set of outdated and misguided claims. Rather than facing (...) up to this conclusion, most recent moral philosophy consists of attempts to find some ways of preserving moral beliefs. This places a contradiction at the heart of moral philosophy. As a resilt it is often impossible to tell whether a contemporary philosopher ultimately rejects or endorses the idea of objective right and wrong. On the basis of a Wittgenstein approach Paul Johnston puts forward an alternative account of ethics that avoids this contradiction and recognises that the central issues of ethics cannot be resolved by conceptual analysis. He then uses this account to highlight the contradictions of important contemporary moral theorists such as Bernard Williams, Alasdair MacIntyre, Thomas Nagel and Charles Taylor. (shrink)