The affinities of antibodies (Abs) for their target antigens (Ags) gradually increase in vivo following an infection or vaccination, but reach saturation at values well below those realisable in vitro. This ‘affinity ceiling’ could in many cases restrict our ability to fight infections and compromise vaccines. What determines the affinity ceiling has been an unresolved question for decades. Here, we argue that it arises from the strength of the chain of protein complexes that is pulled by B cells (...) during the process of Ag acquisition. The affinity ceiling is determined by the strength of the weakest link in the chain. We identify the weakest link and show that the resulting affinity ceiling can explain the Ab affinities realized in vivo, providing a conceptual understanding of Ab affinity maturation. We explore plausible evolutionary underpinnings of the affinity ceiling, examine supporting evidence and alternative hypotheses and discuss implications for vaccination strategies. (shrink)

In the course of an immune response, antibodies undergo affinity maturation in order to increase their efficiency in neutralizing foreign invaders. Affinity maturation occurs by the introduction of multiple point mutations in the variable region gene that encodes the antigen binding site. This somatic hypermutation is restricted to immunoglobulin genes and occurs at very high rates. The precise molecular basis of this process remains obscure. However, recent studies using a variety of in vivo and in vitro (...) systems have revealed important regulatory regions, base motifs that are preferred targets of mutation and evidence that transcription may play an active role in hypermutation. BioEssays 20:227–234, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

In the course of an immune response, antibodies undergo affinity maturation in order to increase their efficiency in neutralizing foreign invaders. Affinity maturation occurs by the introduction of multiple point mutations in the variable region gene that encodes the antigen binding site. This somatic hypermutation is restricted to immunoglobulin genes and occurs at very high rates. The precise molecular basis of this process remains obscure. However, recent studies using a variety of in vivo and in vitro (...) systems have revealed important regulatory regions, base motifs that are preferred targets of mutation and evidence that transcription may play an active role in hypermutation. BioEssays 20:227–234, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

In the course of an immune response, antibodies undergo affinity maturation in order to increase their efficiency in neutralizing foreign invaders. Affinity maturation occurs by the introduction of multiple point mutations in the variable region gene that encodes the antigen binding site. This somatic hypermutation is restricted to immunoglobulin genes and occurs at very high rates. The precise molecular basis of this process remains obscure. However, recent studies using a variety of in vivo and in vitro (...) systems have revealed important regulatory regions, base motifs that are preferred targets of mutation and evidence that transcription may play an active role in hypermutation. BioEssays 20:227–234, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

There can be no doubt that a closer study of avidity will be an indispensable step towards understanding the mechanisms of immunity. N. K. Jerne, 1951, p. 1403.

High‐precision tumor targeting with conventional therapeutics is based on the concept of the ideal drug as a “magic bullet”; this became possible after techniques were developed for production of monoclonal antibodies (mAbs). Innovative DNA technologies have revolutionized this area and enhanced clinical efficiency of mAbs. The experience of applying small‐size recombinant antibodies (monovalent binding fragments and their derivatives) to cancer targeting showed that even high‐affinity monovalent interactions provide fast blood clearance but only modest retention time on the target antigen. (...) Conversion of recombinant antibodies into multivalent format increases their functional affinity, decreases dissociation rates for cell‐surface and optimizes biodistribution. In addition, it allows the creation of bispecific antibody molecules that can target two different antigens simultaneously and do not exist in nature. Different multimerization strategies used now in antibody engineering make it possible to optimize biodistribution and tumor targeting of recombinant antibody constructs for cancer diagnostics and therapy. BioEssays 30:904–918, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

The paper is the first of two to be published in Cognitio which explore the hypothesis that the thought of Ralph Waldo Emerson (1803- 1882), brilliantly expounded in the generation before Charles Sanders Peirce (1839-1914), anticipated, if not provided the direct provenance of, Peirce’s mature metaphysical ideas. The papers provide running commentaries on Emerson’s later-phase essays, “Poetry and Imagination” (1854, published in 1876) and “The Natural History of Intellect” (1870). “Poetry and Imagination” is shown to contain the seeds of Peirce’s (...) objective idealism — namely, that “matter is effete mind,” or “mind hide-bound with habits,” — set within an evolutionary cosmology that grounds the human mind’s connaturality or affinity with the laws of nature, a doctrine subtending his abductory logic of scientific discovery. Mutatis mutandis, all these components were already present in Emerson’s essay. Peirce spoke of his “buddhisto-christian religion,” which was another name for Emersonian cosmosemiosis. His originality consisted in applying Emerson’s emphasis on the poetic to the scientific imagination, though the seeds of the latter are present in Emerson’s “The Natural History of Intellect” and other essays as well. (shrink)

First, there are some striking similarities in the history of reception of Fleck’s and Neurath’s ideas. Due to the style of their writings they were not or often not well welcome in their national philosophical communities, i.e., the Vienna Circle and the Lvov-Warsaw School. This is especially true in the case of Fleck. On the other hand, some prominent logical positivists, like Hempel, are to some extent guilty of making of Neurath a clumsy thinker whose ideas needed to be clear (...) by a more mature philosopher, i.e. Carnap. So their work was often considered as non-scientific. With a lack of response their theories were forgotten for many years, and even if not forgotten they were habitually ridiculed by critics. After a long period of seven thin years they have their renaissance. They are even quite popular. In the last 20 years a number of excellent books and papers on Neurath and Fleck have apperared. But one can hardly find a line of comparison. One might say that this is not surprising at all, as there is nothing to compare there. Neurath was a radical positivist while Fleck’s writing were aimed only against neopositivism. Accordingly, these are poles, and all we can say is that they are completely different. But even if Neurath was a follower of radical neopositivism that Fleck was fighting with, there are some common points in their programmes and I will try to show that even if they are in opposition, their paths intersected at certain points. (shrink)

Interleukin 5 (IL‐5) is a kind of peptide hormone released from T lymphocytes of mammals infected with microorganisms or parasites. It is an acidic glycoprotein with a molecular mass of 40 to 50 kDa that consists of a homodimer of polypeptides. It controls hematopoiesis so that it increases natural immunity. In the mouse, IL‐5 acts on committed B cells to induce differentiation into Ig‐producing cells and on common progenitors for CD5+ pre‐B cells and CD5+ macrophages to support their survival. The (...) antibodies secreted by CD5+ B cells seem to be responsible for the primary protection against the infection with microorganisms or parasites. It also supports the growth and/or differentiation of eosinophil precursor and mature eosinophils, which can be effective for the removal of parasites in combination with the antibodies against them. Murine IL‐5 receptor (IL‐5R) consists of two different polypeptide chains; αL chain and β chain. The IL‐5R α chain is 60 kDa protein that binds IL‐5 with low affinity. The IL‐5R β chain is a 130 kDa protein which does not bind IL‐5 by itself but is necessary to form the high affinity IL‐5R. The β chain was identified by using one of the anti‐IL‐5R mAb and anti‐IL‐3R mAb as the IL‐3R homologue. This β chain is also used as the β chain of GM‐CSF receptor. This fact suggests that there is a common signaling mechanism among these cytokines and efficient cooperation among them. At the same time, these findings may explain the overlapping role of these cytokines in the development of granulocytes. (shrink)

The role of antibody-antigen affinity and concentrations in adaptive antibody response is analyzed in a framework of probabilistic inventory model for antibody production. Our results indicate significant differences in optimal behaviours of low, moderate and high affinity groups and offer important implications. Interestingly, the involved approach is also of relevance in other production systems. Directions for its applications in industries and information sciences are also presented.

Human hybridomas secreting monoclonal antibodies (MoAb) reactive with tumor cell antigens were produced in our laboratory by the immortalization of UC 729‐6 with B lymphocytes isolated from regional draining lymph nodes of cancer patients. MoAbs were purified from the hybridoma supernates by standard biochemical procedures for in vivo studies and by affinity methods for in vitro experiments. Using a novel method in the preparation of slides containing adherent tumor cells, immunoreactivities of the MoAbs were evaluated by an indirect immunofluorescence (...) assay. Based on this data, human MoAbs can, therefore, be used as research reagents. (shrink)

Niels Kaj Jerne has proposed the “immune network theory” of interactions among anti‐idiotypic antibodies, able to interfere with humoral responses to certain antigens. After the occurrence of the primary generation of antibodies, against an antigenic epitope, idiotypes of these antibodies induce anti‐idiotypic antibodies that modulate the intensity of the first response, and so on. Adverse effects following SARS‐COV‐2 COVID‐19 vaccines are occasionally similar to the symptoms of COVID‐19 infection. Rare events linked to SARS‐CoV‐2 vaccines also resemble some rarely reported COVID‐19 (...) complications. Safety data from product information by European Medicines Agency suggest that spectra do overlap for four main vaccines. The proposition is that vaccine events and COVID‐19 complications are related to anti‐idiotypic antibodies whose spatial shape can lead to interactions with ACE2 molecules, in individuals with a prolonged Spike protein synthesis. The vaccines target cells by their affinity to the vaccine vector, or to engulf lipid nanoparticles. Anti‐idiotypic antibodies shaped similarly to the Spike protein possibly interact with ACE2 molecules and cause diverse signs and symptoms. (shrink)

The random nature of immunoglobulin gene segment rearrangement inevitably leads to the generation of self‐reactive B cells. Avoidance of destructive autoimmune reactions is necessary in order to maintain physiological homeostasis. However, current central and peripheral tolerance concepts fail to explain the massive number of autoantibody‐borne autoimmune diseases. Moreover, recent studies have shown that in physiological mouse models autoreactive B cells were neither clonally deleted nor kept in an anergic state, but were instead able to mount autoantibody responses. We propose that (...) activation of autoreactive B cells is induced by polyvalent autoantigen complexes that can occur under physiological conditions. Repeated encounter of autoantigen complexes leads to the production of affinity‐matured autoreactive IgM that protects its respective self‐targets from degradation. We refer to this novel mechanism as adaptive tolerance. This article discusses the discovery of adaptive tolerance and the unexpected role of high affinity IgM autoantibodies. (shrink)

Observations suggesting the existence of natural antibody prior to exposure of an organism to the corresponding antigen, led to the natural selection theory of antibody formation of Jerne in 1955, and to the two signal hypothesis of Forsdyke in 1968. Aspects of these were not only first discoveries but also foundational discoveries in that they influenced contemporaries in a manner that, from our present vantage point, appears to have been constructive. Jerne's later hypothesis (1971, European Journal of Immunology (...) 1: 1-9), that antibody-like receptors on lymphocytes were selected over evolutionary time for reactivity with the major histocompatibility complex (MHC) antigens of the species, was a first, but it was incorrect, and was foundational only to the extent that it emphasized the need to explain the Simonsen phenomenon. Although easily construed as derivative of Jerne (1971), the affinity/avidity model of Forsdyke (1975, Journal of Theoretical Biology 52: 187-198), which predicted that cell-surface components, including MHC antigens, would restrict antigen-reactivity by somatically shaping lymphocyte repertoires, was actually an extension of the two signal hypothesis. While presenting a mechanism for the positive selection of lymphocyte repertoires, and explaining the Simonsen phenomenon, the affinity/avidity model was not foundational in that it had to be independently rediscovered. For science to advance optimally we must seek to close temporal gaps so that first discoveries are also foundational. Listening to young scientists may be part of the solution. (shrink)

The book reconstructs the history of Western ethics. The approach chosen focuses the endless dialectic of moral codes, or different kinds of ethos, moral doctrines that are preached in order to bring about a reform of existing ethos, and ethical theories that have taken shape in the context of controversies about the ethos and moral doctrines as means of justifying or reforming moral doctrines. Such dialectic is what is meant here by the phrase ‘moral traditions’, taken as a name for (...) threads of moral discourse, made in turn of other interwoven threads, including transmission of shared codes, appeals to reform of prevailing custom, rational argument about the justification of some precept on the basis of some shared general teaching or principle, and rational argument about the ultimate basis for principles and justification of authoritative teaching. That is, the approach adopted to the reading of ethical texts depends on a firm belief in the fact that philosophers hardly created any ethical doctrine out of nothing. The main point this book tries to highlight is how different philosophical theories emerged and followed each other as a result of attempts at accounting for what was going on in the world of moral traditions. Changes were propelled by controversies between different schools, and highly abstract arguments were the unintended effects of moves made by controversialists forced to transform (and occasionally to turn upside down) their own doctrines in order to face the challenge posed by other arguments. This is the reason why the book examines not only texts that already enjoy pride of place in the history of philosophy (Aristotle, Kant, Hegel), but also other texts usually treated in the histories of religions (the Bible, the Talmud, the Quran), and others considered to be much less philosophical (Plutarchus, Pufendorf). -/- 1. Plato and a response to ethical scepticism. Two different traditions of morality in VI-V century Greece are described. The birth of philosophical questioning of traditional morality and temporal and spatial variation of custom is described within the context of the v century crisis, the demise of traditional aristocratic and tyrannical rule and the birth of democracy. Two conflicting answers to the challenge are reconstructed, namely conventionalist or immoralist theories formulated by the Sophists and the eudemonist and intellectualist Socratic theory. Plato’s own reformulation of Socrates answer to the Sophists is reconstructed. His psychological views, his classification of the four cardinal virtues and his political theory are described as parts of a unitary system, culminating in an extremely realist moral ontology identifying the idea of the good with the essence of the (moral and extra-moral) world itself. -/- 2. Aristotle and the invention of practical philosophy. Aristotle’s invention of practical philosophy as a field separated from first philosophy is shown to be an implication of his break with Plato moral ultra-realism. Aristotle’s agenda in his moral works is arguably dependent on a polemical intention, namely dismantling Socratic intellectualism. The semi-inductive or virtuously circular method of practical philosophy is illustrated, starting with the received opinions of the better and wiser individuals and trying dialectically to sift what is left of mistake and inconsistence in such opinions, finally trying to correct mistakes and make the overall practical science more consistent. The chapter illustrates then the relationship of individual ethics, or ‘monastics’, with the art and the science of the pater familias, or ‘economics’, and the science of the ruler and citizen, or politics. The nature of virtues, or better, excellences of character, is discussed, highlighting the basic role of hexis, or ‘disposition’. Prudence, or better practical wisdom, is the focus of the chapter. Its relationship with bouleusis or deliberation is examined, and its autonomous status vis-à-vis theoretical knowledge is stressed. -/- 3. Diogenes and philosophy as a way of life. The chapter provides an overview of Hellenistic ethics, which almost amounts to Hellenistic schools of philosophy, in so far as ‘philosophy’ became in these centuries primarily the name for a way of life. The typical character of the Cynical movement is highlighted, that of a school of life, not a school aimed at providing any kind of intellectual training was to be provided. -/- 4. Epicurus and ethics as self-care. The peculiar character of the Epicurean school is described, a combination of a science of well-being aiming, more than at pleasure as in the popular view, at reduction of useless suffering, of unnecessary needs, and at a balanced selection of pleasures of the best and most durable kind. -/- 5. Epictetus and ethics as therapy of the passions. The various phases of Stoicism are described, and the shifting place given to ethics in the Stoic system of idea, culminating in the paradoxical view of ethics, its impossibility in principle notwithstanding, as the only truly significant and necessary part of philosophy. Cicero is treated, showing how his own synthesis of various Hellenistic trends is as a truly philosophical enterprise, deserving serious consideration after one or two centuries when he was confined to the role of literate. Epictetus is chosen as the best example of what the Stoic tradition could yield, an art of living based on sophisticated introspection, in turn aimed at making a kind of cognitive therapy possible, dismantling obnoxious passions at their root by systematically correcting false representations. -/- 6. Philo and the reconciliation of Torah and Platonism. A reconstruction of basic ideas from a few books of the Hebrew Bible is provided, starting with the Prophetic tradition and the focus on God’s mercy as the source of motivation and standard for human behaviour. Then a comparative analysis is undertaken of a parallel tradition, namely the three codifications of the Torā (Law or, better, Instruction), highlighting how a core of moral ideas may be recognized as a basis and preamble of codification of civil law, cultural practice, and regulation of ritual purity. The importance of Leviticus is stressed as the turning point when emphasis mercy, typical of the Prophetic tradition, is combined with the legal tradition, yielding the change in sensibility of the Second Temple time. Philo of Alexandria is described as one of the three leading figures – together with Rabbi Hillel and Rabbi Yeshua – at the apex the emergence of the mentioned new sensibility, gradually including mercy as an essential part of justice and establishing the starting point of both the Rabbinic and the Christian tradition. This consists precisely in the precept of one’s neighbour’s love or of the golden rule, two eventually identical precepts whose meaning is arguably more sober and sensible than the long-lasting Christian tradition deriving from John and Augustine has made us believe and no novelty vis-à-vis so-called Ancient-Testament teachings. -/- 7. Augustine and Christianity as Neo-Platonism. The first section examines the moral doctrines of so-called 'ethical Treaties' from the Talmud, a group of treaties, among which the best known is Pirqé Avot, that were left out of the six "orders" of the canon as they did not fit in any of the six groups of issues ritual or legal on which the division was based. According to Maimonides, their peculiar theme is provided by the Deòt, 'opinions', i.e., mental dispositions, that is, the translation of the Greek term hexeis and Arab akhlak (in turn providing in this language the name for ethics as such). The three topics I reconstruct are: i) the notion of Torah: The Torah is understood as the world order itself, or as the ‘Wisdom’ that existed even before creation and was ‘the tool by which the world was built’; however, the Torah is an earthly and human entity, as it was "received" by humans, and from that very moment belongs to them; ii) the relationship between love of God and love of neighbour; the treaties require us to study and practice the Torah ‘for its own sake’, that is, require us to act out of love, not out of fear or hope of reward; iii) the idea of sanctification of daily life: having disappeared with the destruction of the Temple the possibility of any conflict between liturgical service and everyday life, the latter is assumed to be in itself divine service: to give food to the poor has the same value as sacrifices in the Temple, and as an implication, the insistence become recurrent on the goodness of created things in themselves along with a polemic against ascetic currents. The conclusions drawn are: i) the moral teachings of the Talmud and those of Yeshua are, rather than similar, virtually identical; one may safely say that the precept of love and the golden rule are central ones for all Talmudic rabbis, that mercy plays an indispensable role alongside with justice, and the latter is not a different thing from one’s neighbour’s love; ii) a peculiarity of Talmud rabbis facing Yeshua is the idea of study as worship, and knowledge as a source of justice; but this is an idea of Judaism after the Temple's destruction that cannot be attributed to the Pharisees of Yeshua’s time; iii) the relation of study and practice in the Talmud parallels that between faith and deeds in Paul's epistles, that is, respectively faith or learning are a necessary and sufficient condition to be recognized as righteous , but deeds are the inevitable effect of either faith or learning. The sayings ascribed to Yeshua are examined first, yielding the conclusion that a close equivalent may be found for every saying in Talmudic literature and yet the whole is ascribed to one rabbi, with rather consistent stress on God’s mercy and unconditional forgiving as the mark of true imitation of God. Thus, Yeshua’s teaching is pure Judaism. The third section describes briefly the galaxy of Gnostic currents and Manichaeism, trying to sketch the profile of moral teachings resulting from an encounter of Asian spiritual traditions, Hellenistic lore and sparks of teachings from apocalyptic Jewish currents. The last section summarizes the turbulent history of several encounters between Christian currents and Hellenistic philosophical schools. The first one was with late Cynicism. Recent, rather controversial, literature discovered the jargon and a few topics from the Stoic-Cynical popular philosophy in a few books from the New Testament itself. This, far from proving that Rabbi Yeshua had been influenced by cynic preachers, is a proof of the necessity felt by Christian preachers to translate the original ‘Christian’ teaching into a Greek lexicon deeply impregnated with cynic terminology. The second was with Platonism, yielding the mild and temperate moral teaching of Clemens of Alexandria, teaching the sanctity of nature and the human body, the joy of moderate fruition of ‘natural’ kinds of pleasures, and the beauty of the marital life – in short, the opposite of the standard picture of Medieval Christianity. Ambrose of Milan brings about a different kind of synthesis, namely with Middle Platonism, where Stoic themes prevail. The most shocking case is Augustine, where an early Manichean education is overcome in a former phase by a synthesis of Plotinian Neo-Platonism and Christian preaching, yielding a sustained polemic with the Manicheans and rather optimistic views on life and Creation, the body and sexuality, and Hebrew-Judaic tradition not far from Clemens of Alexandria. In a later phase, occasioned by controversy on the opposite front, with such Christian currents as the Pelagians and Donatists, Augustine comes back to heavily anti-Judaic and world-denying ascetic attitudes where is earlier Manichean upbringing seems to emerge again. The tragedy of medieval Christianity will be the later Augustine’s overwhelming influence. A final section is dedicated to the monastic tradition where a curious mixture of world-denying asceticism with an astonishingly penetrating ‘science’ of introspection emerges. -/- 8. Al Farabi and the reconciliation of Islam and Platonism. The Qurān and the qadit, that is, collections of sayings ascribed to the prophet Muhammad contain a wealth of precepts and catalogues of virtues mirroring moral contents from the Jewish and the Christian traditions, among them the basic notion of imitation of the Deity, where mercy is assumed to be its basic trait. An important tradition within Islam, namely Sufism, stressed to the utmost degree the role of mercy, turning Islam into a mystic doctrine centred on retreat from the world, abandonment to God’s will, and a peaceful and fraternal attitude to our fellow-beings. A secular literary tradition originating in the Sassanid Empire, the literature of advice to the Prince had for a time a widespread influence in the newly constituted Arabic-Islamic commonwealth. In a later phase, the legacy of Hellenic philosophy made its way into the intellectual elite of the Islamic world. The first important legacy was Platonic, and the Republic became the main text for Islamic Platonism. Al-Farabi wrote an enjoyable remake of the Platonic Republic, arguing that the citizen’s virtues were the basis on which the political building needs to rest. The secular lawgiver is enlightened by the light of reason in his everyday practice of governance, but room is made for the Prophet as the voice of revealed truth that confirms and completes the rational truth that philosophy may afford. In a second phase also Aristotelian and Stoic influence were assimilated. Miskawayh’s treatise was the masterwork at the time Arabic philosophy reached its Zenith. It is a treatment of the soul’s diseases and their remedies, combining the Aristotelian doctrine of the golden mean with the Stoic doctrine of the passions and elements of Galenic medicine. Towards the eleventh-twelve centuries a war raged among theologians and philosophers, finally won by the former with disappearance of philosophy as such. The newly established mainstream, yet, was no kind of intolerant fanaticism. It drew from the work of mystic theologian Al-Ghazālī, the best heir of Sufism, teaching a tolerant and peaceful attitude to our fellow-beings and a passive attitude to destiny as an expression of the Divine will. -/- 9. Moshe ben Maimon and the reconciliation of Torah and Aristotelian ethics. The encounter between the Talmudic tradition and Hellenic philosophy had taken place a first time in Alexandria at the time of Philo but the two traditions had parted way again. In fact, the kind of Platonic Judaism founded by Philo survived only within Christianity, in the fourth Gospel and then in writings by Clemens of Alexandria. The Talmudic literature had absorbed just less striking traits from the Hellenic Philosophy, namely an idea of ethics as care of the self and a role for the education of character as propaedeutic to theoretical knowledge. In the Arabic-Islamic world, a second round started when Jewish authors writing in Arabic undertook the task to prove the full compatibility of the tradition deriving from Torah and Platonic philosophy. The culmination of this attempt is provided by Moshe ben Maimon who tried to use Aristotelian ethics as a language into which the teaching from the Pirké Avot could be translated. -/- 10. Thomas Aquinas and the reconciliation of Christian morality and Aristotelian ethics. In the first section the fresh start is described of philosophical ethics in Latin Europe at the turn of the Millennium. In a first phase, Anselm and Peter Abelard built on a Platonic and Augustinian legacy. In this phase. remarkable innovations are introduced, including Abelard’s claim of the obliging character of erring consciousness. In a second phase, the rediscovery of Nicomachean Ethics thanks to Latin translation of Arabic versions gives birth to a new wave of ethical studies, recovering the very idea of Aristotelian practical philosophy, with the potential implication of full legitimization of natural morality, i.e. ethics without Revelation. Aquinas’s ethics is a theological ethics out of which it would be vain to try to extract a self-contained philosophical ethics. His treatment of topics in philosophical ethics, yet, does not boil down to repetition of Aristotelian arguments but is rather a creative reshaping of such arguments. For example, he introduces also in the practical philosophy a first principle parallel to the principle of non-contradiction; and he also carries out a synthesis of Aristotelianism, Stoicism, and neo-Platonism. Even though it is essentially moral theology, Aquinas’s doctrine - unlike Augustine – grants full citizenship to "natural" morality, firstly by rejecting the claim that the corruption of human nature due to the original sin is so radical as to leave "pure nature" incapable of moral goodness. The doctrine is presented in a more sophisticated formulation in a few of the Quaestiones, such as De Malo and De Veritate, in the Summa contra Gentes and in the commentaries to Aristotle than in the famous Summa Theologica, but the latter work includes the only or the largest exposition of some decisive part of the theory. Thus, the Summa Theologica should be read for what it is more than criticized for not being what it was not meant to be. It was not meant to be the brilliant synthesis of all that Reason he had been able to produce with what Revelation had added about which the Neo-Thomists used to dream, but rather a manual for the training of preachers and confessors, where theoretical claims are not too demanding and a few serious tensions are left. Besides a jump between the Prima Secundae and the Secunda Secundae, being the former an essay in virtue theory and the latter a handbook for confessors, the most serious tension is perhaps the one between the ethics of right reason presented in most of Ia-IIae and the eudemonistic ethics developed in quaestiones 1-5 of the same part; the alternative ethical theory which also may be found in Augustine, the Stoic view of a cosmic reason eventually coincident with the moral law, was believed by Anselm (followed by John Duns Scotus and William of Ockham) to be incompatible with eudemonism. It is questionable whether Thomas could reduce the tension proving that it is just an apparent tension, in so far as the right reason and bliss derived from knowledge of God tend to coincide, but this is just a conjecture. Thomas’s ethics is a virtue ethic, not a law-based one, and moral judgment focuses on the virtues, particularly charity, not on the commandments and even less on absolute prohibitions; Thomas, however, would not have considered a drastic alternative between law and the virtues such as the one which has been advanced in late twentieth-century philosophy to be justified. Nonetheless, when it discusses ‘special’ virtues, it ceases to be an ethics of virtue and becomes a disappointing and often contradictory discussion of legal and illegal acts. Such a discussion takes most of the time ‘reasonable’ middle positions on controversial issues but not the alternative approach that Aristotelianism would have made possible; even when some occasional Aristotelian claim shows up, such as money’s barrenness as a reason against usury, this seems to be made by an author who apparently ignores the Aristotelian Thomas of the Prima Secundae. It is an ethic of human autonomy which recognizes the binding character of the individual conscience and, potentially, even a duty to disobey unjust laws. It is true that what Thomas writes in his discussion of death penalty and persecution of heretics is simply disgusting, and yet we should blame Thomas the man, not Thomist ethical theory. Finally, Thomas’s ethics is not ethical ‘absolutism’, as both traditionalist Catholic theologians and secularist enemies of dogmatic morality tend to believe. It is instead an ethic of prudential judgment. Exceptions to this approach – or better results of logical fallacies – are such claims as the absolute character of negative precepts and of the existence of "intrinsically evil acts", claims that simply cease to make sense in the light of Thomas’s own distinction between human act and natural act, carrying consequences Thomas did not live long enough to draw or was not consistent enough to dare to draw. -/- 11. Francisco de Vitoria and casuistry. The first topic illustrated is the discussion about the notion of pura natura, namely the human condition after the original sin and before divine revelation. The core notion was already there in Aquinas but was later developed by Caietanus (Thomas de Vio) with a number of interesting implications: firstly a view of human nature as such much more positive than Augustine’s and his followers’ view, including both Calvinists and Jansenists; secondly, the implication that the philosopher’s morality, as opposed to the Christian’s morality, is a quite respectable kind of morality; thirdly, that theocracy and prosecution of the unfaithful lacked justification, with more far-fetching consequences than Aquinas himself had dared to draw. The second topic is casuistry, a new name for a comparatively older way of thinking, which was already there in late Stoicism and Cicero as well as in the Talmudic literature. This is an approach aimed at yielding probable enough solutions for doubtful cases even in absence of completely safe staring points. The genre developed from medieval reference books for confessors and became by the sixteenth-century a sophisticated tool-box for dealing with various fields of applied ethics. Francisco Vitoria, the main authority of Baroque Scholasticism, was a controversial figure, among the proponents of the new discipline of casuistry and a consistent proponent of more separation between the religious and the civil authority, stricter limits to the legitimacy of war, innate rights of non-Christian nations in the New World based on the notion of pura natura, providing a standard of ‘natural’ goodness, previous to revelation, on which the Indian nations were judged to live in a naturally good condition, provided with the institutions of family, justice, and religion had accordingly a right to full respect by Christian sovereigns. Bartolomé de Las Casas, arguing along similar lines, was the leader of a historical battle in defence of the rights of the Indios. -/- 12. Michel de Montaigne and the art of living. A short description of one of the Renaissance Phyrronism, one of the classical philosophies revived in the fifteenth and sixteenth century. Montaigne combines the sceptical epistemology with an understanding of ethics – indeed of philosophy as a whole – in terms of an art of living inspired by two basic ideas, sagesse, that is, practical wisdom as the only kind of rationality available after theology, science, and tradition have declared bankrupt, and an aesthetic ideal of self-transformation through the art of writing and introspection. -/- 13. Pierre Nicole and neo-Augustinianism. The chapter illustrates first the vicissitudes of Augustinianism newly born after the late medieval triumph of Thomist Aristotelianism in the alternative Protestant and Catholic versions processed by the Calvinists and the Jansenists. Then it illustrates the doctrines of Pierre Nicole, Blaise Pascal’s best disciple, on the impossibility of introspection, on the ubiquity of self-deception, on the incurably evil character of the passion of love, and on the two moralities, the one of the man of the world, the morality of honesty which is indispensable for granting peace and order but devoid of any true value for eternal salvation, since the same external behaviour may be prompted by opposite motivations, and the morality of charity, the only true one but also useless to society. The third topic is Pierre Malebranche’s view of self-deception as a ubiquitous phenomenon accounting for human action and responsibility and his reformulated theory of self-love, no less ubiquitous than for Nicole and yet not as incurably evil, given the distinction between morally indifferent and even necessary amour de soi and vicious amour proper, a distinction on which the whole of Rousseau’s moral and political theory rests. -/- 14. Samuel von Pufendorf and the new science of morality. The chapter is dedicated to the discovery of the idea of a ‘new moral science’. Hugo Grotius is discussed first highlighting the real character of his project, much closer to the Thomist idea of a natural law accessible to non-corrupted human reason when human beings are living in a state of pura natura. Then Hobbes’s combination of scepticism, voluntarism, and conventionalism is described and both the continuity with Grotius’s new science, in the search for non-revealed rational morality, and the break with him, in the adoption of voluntarism and refusal of an intellectualist view of natural law, are illustrated. Pufendorf’s work is illustrated as a synthesis of the two previous attempts and the – up to Schneewind underestimated – paradigmatic example of the new science of morality. -/- 15. Richard Cumberland and consequentialist voluntarism. The chapter gives an overview of eighteenth-century Anglican ethics, noticing how the Cambridge tradition gave special weight to natural theology as opposed to positive or revealed theology – and how two Cambridge fellows, John Gay and Thomas Brown, elaborated on Cumberland’s (and Malebranche’s, as well as Leibniz’s) strategy for finding a third way between intellectualist view and voluntarist view of the laws of nature. The result of their elaboration was a kind of a rational-choice account of the origins of natural laws, where a law-giver God chooses among a number possible sets of laws on a maximizing criterion, and God’s maximandum is happiness for his creatures. The chapter notices also how such a solution aimed at solving at once the problem of evil and that of the foundation of moral obligation by proving how God’s choice was justified as far as it was the one minimising the amount of suffering in the world. 16. Richard Price and intuitionism. The chapter describes first the doctrines of the Cambridge Platonists, an example of hyper-rationalist reaction to Calvinism. Secondly it describes the sophisticated and universally ignored – from Sidgwick to Anscombe –version of what was later labelled ‘ethical intuitionism’ – showing how it escapes familiar objections and misrepresentations of intuitionism – from Mill to Rawls – in grounding its argument on transcendental arguments while carefully avoiding recourse to introspection and psychological evidence, which has been taken as a too easy target by critics of intuitionism. Thirdly, the chapter discusses Whewell’s ‘philosophy of morality’, as opposed to ‘systematic morality’, not unlike Kant’s distinction between a pure and an empirical moral philosophy. Whewell worked out a systematization of traditional normative ethics as a first step before its rational justification; he believed that the point in the philosophy of morality is justifying a few rational truths about the structure of morality such as to rule hedonism, eudemonism, and consequentialism; yet a system of positive morality cannot be derived solely from such rational truths but requires consideration of the ongoing dialectics between idea and fact in historically given moralities. Whewell’s intuitionism turns out closer to Kantian ethics than commentators have made us believe until now, and quite different from what Sidgwick meant by intuitionism. -/- 17. Adam Smith and the morality of role-switch. The chapter describes first, Hutcheson’s attempt at basing the ‘new science’ of natural law on different bedrock than Pufendorf and the English Platonists, namely a moral sense, a faculty whose existence is assumed to be proved on an empirical basis. The second step is a reconstruction of Hume’s rejoinder in terms of a new science of man including morality on an ‘experimental’ basis, that is, a ‘Newtonian’ hypothetical-deductive approach, distinguished from Hutcheson’s allegedly uncritical descriptive approach to human nature. The third step is a reconstruction of Adam Smith theory of morality understood as emerging from a spontaneous interplay of exchanges of situations (the most basic meaning of the word ‘sympathy’ as construed by this author). -/- 18. Jeremy Bentham and utilitarianism. The bulk of the chapter is dedicated to the doctrines of Jeremy Bentham. The Enlightenment spirit that suggested the idea of a new morality, free from religion, is illustrated. The notion of utility is illustrated as well as the subsequent formulations of the principle of utility. The idea of felicific calculus is discussed, showing how its inner difficulties prompted several reformulations of the principle of utility in order to avoid undesirable implications of proposed formulations. The role of the thesis of spontaneous convergence between interest and duty is discussed, showing how it left numberless questions open, and the distinction between the virtues of prudence, justice and beneficence is described as a way out of the deadlocks of classical utilitarianism. After Bentham, Mill’s reformed utilitarianism is reconstructed, showing how it is a kind of mixed system – as closer to common sense as it gives up Bentham’s claims to consistency and simplicity – resulting as unintended consequences from the controversies in which Mill was too keen to engage. The hidden agenda of the controversy between Utilitarianism and Intuitionism, going beyond the image of the battle between Prejudice and Reason, is described, showing how both competing philosophical outlooks turn out to be more research programs than self-contained doctrinal bodies, and such programs appear to be implemented, and indeed radically transformed while in progress thanks to their enemies no less than to their supporters. -/- 19. Immanuel Kant, practical reason and judgment. The chapter argues that Kant took from Moses Mendelssohn the idea of a distinction between geometry of morals and a practical ethic. He was drastically misunderstood by his followers precisely on this point. He had learned from the sceptics and the Jansenists the lesson that men are prompted to act by deceptive ends, and he was aware that human actions are also empirical phenomena, where laws like the laws of Nature may be detected. His practical ethics made room for judgment as a holistic procedure for assessing the saliency of relevant moral qualities in one given situation; this procedure yields the same results as the geometry of morals does for abstract cases but does so immediately and without balancing conflicting duties with each other, since what makes for the salient quality of a situation is perceived from the very beginning. Kant's practical philosophy is richer than the received image, making room for an ‘empirical moral philosophy’ or moral anthropology including treatment of commerce, needs, value and price, happiness and well-being; the overall social theory and philosophy of history is less different from Adam Smith's than the received image makes believe; the paradox of happiness is central to Kant's philosophy; a distinction between happiness and well-being is clearly drawn; the distinction plays a basic role in establishing a link between the economic and the moral life. -/- 20. Georg Wilhelm Friedrich Hegel and the critique of abstract universalism. The chapter describes first the Romantic movement and the implications some of its concerns, rescuing passions, community, tradition, the individual as the bearer of a unique destiny, and the longing for organic unity between the individual, mankind and nature. Hegel’s contribution is discussed then, highlighting how, on the one hand, he shared a number of these concerns and on the other he had more rationalist leanings. The notion of morality is the pivotal point of the reconstruction, highlighting how Hegel construes this notion as a key to his own diagnosis of the malaise of modernity – the separation of individual and Gemeinschaft – and how his attack on Kant turns around this very idea. -/- 21. Friedrich Nietzsche against Christianity and the Enlightenment. The chapter illustrates first the idea of deconstruction of the back-world of values. Nietzsche claims to be legitimate heir of the French moralists, Leibniz, Kant and Hegel, in so far as he allegedly carries out to its deepest implications their discovery of what lies behind traditional naïve belief in the existence of an objective realm of values just waiting for description by the philosopher. The two exemplars form which genealogy draws inspiration are the classical philologist’s historical reconstructions of lost meanings and the chemist’s decomposition of elements. Then the genealogy of the notions of good and evil carried out in the first dissertation of Genealogy of morals is illustrated with its paradoxical conclusion that will to power is in fact the only ‘genuine’ kind of goodness. The third point illustrated is the dialectic of ascetism and self-realization with its ambiguous outcome. The suggested interpretation of such outcome is that Nietzsche’s normative ethics is a kind of virtue ethics taking an aesthetic ideal as a normative standard -/- 22. George Edward Moore and ideal utilitarianism. The chapter discusses the ideas of common sense and common-sense morality in Sidgwick. I argue that, far from aiming at overcoming common-sense morality, Sidgwick aimed purposely at grounding a consist code of morality by methods allegedly taken from the natural sciences to reach, also in ethics, the same kind of “mature” knowledge as in the natural sciences. His whole polemics with intuitionism was vitiated by the a priori assumption that the widespread ethos of the educated part of humankind, not the theories of the intuitionist philosophers, was what was worth considering as the expression of intuitionist ethics. In spite of a naïve positivist starting-point, Sidgwick was encouraged by his own approach in exploring the fruitfulness of coherentist methods for normative ethics. Thus, Sidgwick left an ambivalent legacy to twentieth-century ethics: the dogmatic idea of a “new” morality of a consequentialist kind, and the fruitful idea that we can argue rationally in normative ethics albeit without shared foundations. Then it reconstructs the background of ideas, concerns and intentions out of which Moore’s early essays, the preliminary version, and then the final version of Principia Ethica originated. I stress the role of religious concerns, as well as that of the Idealist legacy. I argue that PE is more a patchwork of rather diverging contributions than a unitary work, not to say the paradigm of a new school in Ethics. I add a comparison with Rashdall’s almost contemporary ethical work, suggesting that the latter defends the same general claims in a different way, one that manages to pave decisive objections in a more plausible way. I end by suggesting that the emergence of Analytic Ethics was a more ambiguous phenomenon than the received view would make us believe, and that the wheat (or some other gluten-free grain) of this tradition, that is, what logic can do for philosophy, should be separated from the chaff, that is, the confused and mutually incompatible legacies of Utilitarianism and Idealism. -/- 23. Edmund Husserl and the a-priori of action. The chapter illustrates first the idea of phenomenology and the Husserl’s project of a phenomenological ethic as illustrated in his 1908-1914 lectures. The key idea is dismissing psychology and trying to ground a new science of the a priori of action, within which a more restricted field of inquiry will be the science of right actions. Then the chapter illustrates the criticism of modern moral philosophy carried out in the 1920 lectures, where the main target is naturalism, understood in the Kantian meaning of primacy of common sense. The third point illustrate is Adolph Reinach’s theory of social acts as a key the grounding of norms, a view that basically sketches the very ideas ‘discovered’ later by Clarence I. Lewis, John Searle, Karl-Otto Apel and Jürgen Habermas. A final section is dedicated to Nicolai Hartman, who always refused to define himself a phenomenologist and yet developed a more articulated and detailed theory of ‘values’ – with surprising affinities with George E. Moore - than philosophers such as Max Scheler who claimed to Husserl’s legitimate heirs. -/- 24. Bertrand Russell and non-cognitivism. The chapter reconstructs first the discussion after Moore. The naturalistic-fallacy argument was widely accepted but twisted to prove instead that the intuitive character of the definition of ‘good’, its non-cognitive meaning, in a first phase identified with ‘emotive’ meaning. Alfred Julius Ayer is indicated as a typical proponent of such non-cognitivist meta-ethics. More detailed discussion is dedicated to Bertrand Russell’s ethics, a more nuanced and sophisticated doctrine, arguing that non-cognitivism does not condemn morality to arbitrariness and that the project of a rational normative ethics is still possible, heading finally to the justification of a kind of non-hedonist utilitarianism. Stevenson’s theory, another moderate version of emotivism is discussed at some length, showing how the author comes close to the discovery of the role of a pragmatic dimension of language as a basis for ethical argument. Last of all, the discussion from the Forties about Hume’s law is described, mentioning Karl Popper’s argument and Richard Hare’s early non-cognitivist but non-emotivist doctrine named prescriptivism. -/- 25. Elizabeth Anscombe and the revival of virtue ethics. The chapter discusses the three theses defended by Anscombe in 'Modern Moral Philosophy'. I argue that: a) her answer to the question "why should I be moral?" requires a solution of the problem of theodicy, and ignores any attempts to save the moral point of view without recourse to divine retribution; b) her notion of divine law is an odd one more neo-Augustinian than Biblical or Scholastic; c) her image of Kantian ethics and intuitionism is the impoverished image manufactured by consequentialist opponents for polemical purposes and that she seems strangely accept it; d) the difficulty of identifying the "relevant descriptions" of acts is not an argument in favour of an ethics of virtue and against consequentialism or Kantian ethics, and indeed the role of judgment in the latter is a response to the difficulties raised by the case of judgment concerning future action. A short look at further developments in the neo-naturalist current is given trough a reconstruction of Philippa Foot’s and Peter Geach’s critiques to the naturalist-fallacy argument and Alasdair MacIntyre’s grand reconstruction of the origins and allegedly unavoidable failure of the Enlightenment project of an autonomous ethic. -/- 26. Richard Hare and neo-Utilitarianism. The chapter addresses the issue of the complex process of self-transformation Utilitarianism underwent after Sidgwick’s and Moore’s fatal criticism and the unexpected Phoenix-like process of rebirth of a doctrine definitely refuted. A glimpse at this uproarious process is given through two examples. The first is Roy Harrod Wittgensteinian transformation of Utilitarianism in pure normative ethics depurated from hedonism as well as from whatsoever theory of the good. This results in preference utilitarianism combined with a ‘Kantian’ version of rule utilitarianism. The second is Richard Hare’s two-level preference utilitarianism where act utilitarianism plays the function of eventual rational justification of moral judgments and rule-utilitarianism that of action-guiding practical device. -/- 27. Hans-Georg Gadamer and rehabilitation of practical philosophy. The post-war rediscovery of ethics by many German thinkers and its culmination in the Sixties in the movement named ‘Rehabilitation of practical philosophy’ is described. Among the actors of such rehabilitation there were a few of Heidegger’s most brilliant disciples, and Hans-Georg Gadamer is chosen as a paradigmatic example. His reading of Aristotle’s lesson I reconstructed, starting with Heidegger’s lesson but then subtly subverting its outcome thanks to the recovery of the central role of the notion of phronesis. -/- 28. Karl-Otto Apel and the revival of Kantian ethics. Parallel to the neo-Aristotelian trend, there was in the Rehabilitation of practical philosophy a Kantian current. This started, instead than the rehabilitation of prudence, with the discovery of the pragmatic dimension of language carried out by Charles Peirce and the Oxford linguistic philosophy. On this basis, Karl-Otto Apel singled out as the decisive proponent of the linguistic and Kantian turn in German-speaking ethics, worked out the performative-contradiction argument while claiming that this was able to provide a new rational and universal basis for normative ethics. An examination of his argument is some detail is offered, followed by a more cursory reconstruction of Jürgen Habermas’s elaboration on Apel’s theory. -/- 29. John Rawls and public ethics as applied ethics. Rawls’s distinction between a “political” and a “metaphysical” approach to one central part of ethical theory, namely the theory of justice, is interpreted as a formulation of the same basic idea at the root of both the principles approach and neo-casuistry, both discussed in the following chapter, namely that it is possible to reach an agreement concerning positive moral judgments even though the discussion is still open – and in Rawls’ view never will be close – on the basic criteria for judgment. -/- 30. Beauchamp and Childress and bioethics as applied ethics. The chapter presents the revolution of applied ethics while stressing its methodological novelty, exemplified primarily by Beauchamp and Childress principles approach and then by Jonsen and Toulmin’s new casuistry. -/- . (shrink)

The article discusses the affinity of the ideas of two prominent Russian scholars N.N. Moiseev and V.S. Stepin. This affinity of their ideas is above all expressed in the global scale of their thinking, in their orientation toward the search for the ways of mankind development. Both thinkers sought a way out of the limitations and crisis of technological civilization through the promotion of basic values of harmony in the evolution of society and the biosphere. They made an (...) enormous contribution to the development of both humanitarian and natural sciences areas of knowledge related to social management and development, techonology, economics, law, medicine, ecology, education, etc. They worked in an interdisciplinary areas and were successful integrators of natural science and humanities. Simultaneously with the scientific work, Moiseev and Stepin were excellent teachers and mentors of both young and mature researchers. They have created successful scientific schools that include many dozens of outstanding scientists. They devoted much attention and much time to social work, primarily in various structures of the Russian Academy of Sciences. The affinity of Moiseev’s and Stepin’s ideas is shown in four areas of their activities: overcoming the crisis of technological civilization and the limitations of the concept of sustainable development, research into socio-humanitarian cybernetics, development of advanced education models, implementation of successful scientific diplomacy projects. The author of this article participated in joint research projects with Moiseev and Stepin, the personal communication with them and their ideas significantly influenced author’s life path, interests and research results. (shrink)

Observations suggesting the existence of natural antibody prior to exposure of an organism to the corresponding antigen, led to the natural selection theory of antibody formation of Jerne in 1955, and to the two signal hypothesis of Forsdyke in 1968. Aspects of these were not only first discoveries but also foundational discoveries in that they influenced contemporaries in a manner that, from our present vantage point, appears to have been constructive. Jerne’s later hypothesis (1971, European Journal of Immunology (...) 1: 1–9), that antibody-like receptors on lymphocytes were selected over evolutionary time for reactivity with the major histocompatibility complex (MHC) antigens of the species, was a first, but it was incorrect, and was foundational only to the extent that it emphasized the need to explain the Simonsen phenomenon. Although easily construed as derivative of Jerne (1971), the affinity/avidity model of Forsdyke (1975, Journal of Theoretical Biology 52: 187–198), which predicted that cell-surface components, including MHC antigens, would restrict antigen-reactivity by somatically shaping lymphocyte repertoires, was actually an extension of the two signal hypothesis. While presenting a mechanism for the positive selection of lymphocyte repertoires, and explaining the Simonsen phenomenon, the affinity/avidity model was not foundational in that it had to be independently rediscovered. For science to advance optimally we must seek to close temporal gaps so that first discoveries are also foundational. Listening to young scientists may be part of the solution. (shrink)

Thy‐1 is a small glycoprotein of 110 amino acids which, folded in the characteristic structure of an immunoglobulin variable domain1, are anchored to the plasma membrane via a glycophosphatidylinositol (GPI) tail(2,3) (Fig. 1). It is a major component of the surface of various cell types, including neurons, at certain stages of their development (4). These qualities doubtlessly appeal to certain cognoscenti, but it is not clear why they would raise Thy‐1 to the status of a favourite molecule. Indeed, few scientists (...) readily admit to having a favourite. We study individual molecules because science is rooted in specific observations; but we do so in order to discover mechanisms of general importance. A molecule's appeal is dependent on its ability to reveal novel aspects of how nature works.Thy‐1 has been unusual in this respect. It was the first lymphocyte surface antigen shown to be restricted to a functional subset of lymphocytes (T cells in the mouse), a finding crucial to the development of cellular immunology(5); it was one of the first cell surface molecules to be sequenced and indicated the importance of immunoglobulin domains and GPI anchors as structural motifs(1–3); it has been pivotal in studies demonstrating that GPI‐anchored molecules are able to signal across the membrane they do not span(6, 7). Thy‐1 has revealed this much, however, with the charm of an adroit stripper: it has always promised glimpses of things more exciting than that displayed. In particular, the function of this molecule has never emerged.Our current work on Thy‐1 in the nervous system is, we believe, finally prizing this last secret into the open. It suggests that Thy‐1 on the neuronal surface interacts with one of the main glial types of adult brain, the astrocyte, to restrict axonal growth(8). There is no current consensus that astrocytes do regulate such growth, and this is the wider question we are addressing from the perspective of Thy‐1. At issue also is how to progress from knowing the nature of a molecule to defining its function. This task has already been achieved with molecules which were harder to characterise than Thy‐1. The problem is a classic Catch 22 situation: Thy‐1 has been readily characterised because it is small and abundant it is ten times more abundant than any other surface glycoprotein on rat thymocytes(9); but since there is so much of it, whatever it does it must do rather badly (or there would be no need to have so much of it!). Defining a function based on low activity or affinity is not trivial.Here I describe two aspects of work on Thy‐1. One is long completed ‐ the research which led to Thy‐1 being isolated and characterised ‐ and included because it demonstrates features which are still applicable to much research using a antibodies today. The other is our ongoing work on the nervous system, which is at that exciting early stage where hypotheses are formed, but the answers are still coming in. (shrink)

The repertoire of acceptor glycoproteins for concanavalin A expressed by a cultured tumour cell reflects the normal developmental lineage from which it was derived, as well as the degree of maturation along that lineage. Antibodies to this particular set of glycoproteins show a considerable specificity towards normal differentiation antigens which are often preferentially associated with the less mature intermediates of the corresponding pathway. In addition, comparisons between ‘immature’ and ‘mature’ tumour cells can be used to identify glycoproteins associated with (...) specific differentiated functions such as secretion. Thus tumour cell glycoproteins provide useful probes for analysis of the molecular biology of development and differentiation. (shrink)

As is well known, Roman Ingarden and Edith Stein had a deep intellectual relationship and friendship, which began during their stay in Göttingen and Freiburg. The time spent together during this period and the correspondence that they maintained over the following years allowed them to be in close contact with their respective philosophies and to influence each other. This article aims at illustrating the affinities between Ingarden’s description of soul in § 78 of Controversy over the Existence of the World (...) and the analysis of soul and psyche developed by Stein between 1916 and 1922. Furthermore, it aims at presenting the hypothesis that this analysis influenced the formal anthropology elaborated by the Polish philosopher many years later. Both the depiction of the soul as a personal nucleus that manifests itself in human lived experiences and the description of this manifestation through the notion of “force” are theoretical elements that are essential in Ingarden’s mature ontology of man and that already played a crucial role in Stein’s early writings. Both thinkers, within several years of one another, elaborated an anthropological view that does not have the life of consciousness as a primary guideline, but that brings to light the ontological relevance of the unitary psychic source of human dispositions, of human character, and of consciousness itself. (shrink)

Throughout his career, the problems that attracted Louis Pasteur almost invariably involved considerations of specificity of structure and/or of action. Thus, his work on asymmetric crystals showed that chemical form not only specifies crystalline structure, but affects the affinity of ferments as well. In his studies of diseases of silkworms, of beer, and of wine, he could unerringly distinguish with the microscope the specific agents of disease. From this emerged his concept of the specificity of species and against the (...) nonspecificity of spontaneous generation, whence the germ theory of disease. It was in the new field of immunology, however, where the manifestations of an exquisite specificity were most clearly seen. Here, Pasteur's vaccines worked because he chose the specific pathogen in order to induce a specific immunity, and he succeeded each time. But the two most prominent Pastorian successors in immunology, Elie Metchnikoff and Jules Bordet, were not equally successful. Although each contributed significantly to the birth of immunology, each advanced a theory that neglected the principle of specificity and paid a price in consequence. Metchnikoff's phagocytic theory of immunity could not survive the demonstrable specificity of humoral antibodies, while Bordet's physical adsorptive concept of the antibody-cell interaction quickly fell to Paul Ehrlich's demonstration of the stereochemical determination of immunological specificity. (shrink)

This article shows buber's dialogue with taoism, Hinduism, And buddhism, How they influenced him, And how this dialogue entered into the progressive stages of his thought. Neither hinduism nor buddhism remains a central part of buber's later thought as do taoism, Hasidism, And zen, But they do play an important part in his early developmental thinking. When he reached his mature philosophy of dialogue, He transcended his early partiality for non-Dualistic vedanta. But taoism, And especially wu-Wei, Action of the whole (...) being, Remained central to the i-Thou relationship, As did buber's affinity for the other "mysticisms of the particular," zen buddhism and hasidism. (shrink)

Play is typically associated with carefree or frivolous activity, yet Nietzsche makes surprising claims about the nature of play. He insists that playfulness is the appropriate attitude for addressing the challenges of human life, and he describes maturity as the ability to play seriously like children. To understand Nietzsche’s serious play, some have emphasized the affinity between play and fiction. Notably, Nadeem Hussain has offered a fictionalist interpretation, according to which nothing has value in itself and valuing resembles make-believe. (...) I hold that illusions and fictions misconstrue Nietzsche’s play and values. In this paper I argue that Nietzsche embraces play in the context of nihilism, which he considers the fundamental problem of modernity. Play ultimately proves central to Nietzsche’s strategy to avert nihilism. I explicate his comments on play, and I use the features of play to illuminate Nietzsche’s response to nihilism found in his enigmatic project of value creation. (shrink)

In the 1930s Warburg's spare prose and disciplined respect for the facts set the style for a new generation of biochemists who had not known the conceptual revolutions of earlier years. Led by Warburg, they rejected the excesses of the colloid school and the false starts of the teens and twenties. Talk of active structure virtually disappeared as chemists began to identify enzymes, coenzymes, vitamins, and hormones. In the gradual transformation of the Atmungsferment from an ironcolloid complex to a specific (...) haem-protein, the roots of Warburg's inspiration were readily forgotten-the richer and more varied intellectual currents of the early decades of biochemistry. Experimental cytology and pharmacology were important strands. Most of what Warburg was doing on narcosis from 1908 to 1912 was typical of this school. He was deeply influenced by Loeb and his theory of the fertilization membrane. In the period from 1900 to 1914 the ups and down of belief in Hofmeister's enzyme theory was an important trend which helped determine the style of biochemistry in later decades. Warburg's conception of the Atmungsferment was shaped by the general reaction c. 1910 against Buchner's optimistic view. Warburg's Heidelberg lecture was framed as an answer to Hofmeister's lecture of 1901 and turned out almost as an imitation or second edition of it. It was a style that was soon out of fashion. The affinity between the early concept of enzymes and the old concept idea of “living protein” should not be neglected in discussions of Warburg's distaste for “enzymology.” The colloid school is too easily dismissed as a mere impediment to the chemical triumphs of the 1930s. Warburg's Atmungsferment was obviously colored by the colloidal cast of biochemical thought in 1912. The Atmungsferment represented, in short, a hybrid transition from the romantic biochemistry of the period 1900–1925 to the mature, classical of the 1930s. It is fascinating precisely because it reflects, and refracts through a unique and powerful mind, the varied local traditions of the early history of modern biochemistry. (shrink)

This paper offers an exposition of Husserl's mature philosophy of mathematics, expounded for the first time in Logische Untersuchungen and maintained without any essential change throughout the rest of his life. It is shown that Husserl's views on mathematics were strongly influenced by Riemann, and had clear affinities with the much later Bourbaki school.

Among the instances of apparent illiberality in Plato's Republic, one stands out as especially curious. Long before making a forced return to the cave, and irrespective of the kinds of compulsion operative in such a homecoming, the philosopher-king has been compelled to apprehend the Good (Rep. VII.519c5-d2, 540a3-7). Why should compulsion be necessary or appropriate in this situation? Schooled intensively through the decades for an eventual grasping of the Good, beginning already with precognitive training in music and art calculated to (...) equip the guardian with a natural affinity towards the good and beautiful (Rep. III.401d3-402a4), the fully mature guardian might be expected to leap towards the Good when it is first opportune. For the Good is, according to Plato, the greatest thing to be learned (megiston mathêma; Rep. VI.504e4-5, 505a2). Reflection on these questions permits us to develop a richer appreciation of the forms of necessitation and compulsion Plato envisages for his guardians, which turn out to be primarily merely hypothetical instances of nomic necessitation. It follows that many of Plato's appeals to compulsion are neither coercive nor objectionably authoritarian. (shrink)

Michel Dalissier Comment entendre la maturité? Est-ce en l’opposant à l’immaturité? La notion se dit-elle en plusieurs sens? Sur qui ou quoi porte-t-elle? Et quels sont ses domaines de manifestation? Dans cette étude, nous examinons en quoi Maurice Merleau-Ponty apporte une réponse originale à ces questions. Il établit que la maturité se conquiert dans l’oeuvre en cours de l’artiste. Elle constitue une prise de conscience, laquelle fait gravir un degré et franchir un point crucial à notre lecture du monde et (...) des autres. Un tel mouvement de la maturité s’affine conceptuellement en une trop longue maturation qui habite un processus d’apprentissage, historique et perceptif, ainsi qu’un mûrissement de la pensée, lent et confronté à des limites intrinsèques. En cette facticité qui est aussi anticipation, la maturité devient essentiellement une prématuration, laquelle n’a rien de prématuré pour la psychanalyse, la politique et la philosophie. (shrink)

Anthony Kenny e Orlando Todisco, in due diversi contesti, hanno proposto un originale accostamento tra Wittgenstein e alcuni filosofi francescani. Alla luce di questi studi è possibile chiedersi quale valore possa avere la nozione di francescanesimo wittgensteiniano e quale utilità essa ricopra nell’identificare i caratteri di una filosofia francescana. Nella prima parte considererò l’atteggiamento di Kenny nei confronti di Duns Scoto, le cui tesi, dapprima frettolosamente associate a quelle del neopositivismo, vengono poi adeguatamente contestualizzate all’interno della contrapposizione tra la tradizione (...) neoplatonica-agostiniana e l’aristotelismo radicale nell’Università di Parigi. Nella seconda parte, analizzerò il parallelo suggerito da Todisco tra Wittgenstein e Occam, con particolare attenzione alla filosofia del linguaggio, alla critica alla metafisica e alla nozione di ineffabilità. Dopo aver evidenziato i limiti storiografici di entrambe queste proposte, concluderò sostenendo che il francescanesimo wittgensteiniano non può essere considerato un progetto di ricerca autonomo capace di stabilire delle tesi comuni. Esso comunque non è una mera provocazione, in quanto offre interessanti considerazioni circa una affine modalità di porsi gli interrogativi filosofici da parte di Wittgenstein e dei filosofi francescani. Questo esito permette di identificare alcune condizioni necessarie perché si possa parlare di una filosofia francescana all’interno della storia della filosofia. In two very different contexts, Anthony Kenny and Orlando Todisco have proposed an original combination between Wittgenstein and some Franciscan thinkers. Thanks to their studies it is possible to question the value and the usability of the expression Wittgensteinian Franciscanism in order to identify the features of a Franciscan philosophy. In the first paragraph, I will take the approach of Kenny about Duns Scotus into consideration. At the beginning of his career, Kenny hastily associates Scotus’ theses to the Neo-Positivistic ones, but in his mature works, Kenny adequately contextualizes them within the contrast between, on the one hand, the Neoplatonic-Augustinian tradition and, on the other, the radical Aristotelism held at the Paris University. In the second paragraph, I will study in depth the parallelism suggested by Todisco between Wittgenstein and Occam, paying particular attention to the philosophy of language, to the criticism toward some types of metaphysics, and to the notion of ineffability. After having underlined the historiographic limits of both of these proposals, I will conclude arguing that Wittgensteinian Franciscanism cannot be appreciated as an autonomous research project able to establish common theses. All the same, it is not a mere provocation, in fact it presents interesting considerations about analogous modalities to submit philosophical questions shared between Wittgenstein and Franciscan thinkers. This outcome allows to distinguish some necessary conditions in order to identify a Franciscan philosophy in the history of Western thought. (shrink)

Summary John Stuart Mill's classic tale of disillusionment from a ‘narrow creed’, an overt as much as a covert theme of his Autobiography (London, 1873), has for many years served as a guide to the search for the causes and sources of his ‘enlargement-of-the-utilitarian-creed’ project. As a result, in analyses of Mill's mature views, Samuel Taylor Coleridge—and friends—commonly take centre stage in terms of influence, whereas John's father—James Mill—is reduced either to a supernumerary or a villain in the last act (...) of John's intellectual development. However, students of Mill's works should not take at face value the story presented in Autobiography. Mill's own emphasis on the role of his ‘new influences’ has led scholars to disregard the role of his ‘old influences’ in his attempt to create a broader theory of living—one which takes into account both the intellectual and the emotional capacities of individuals. A close look at key aspects of John Stuart Mill's ‘enlargement project’ suggests that James Mill may have played a more positive role than is usually acknowledged. A way into the intellectual affinity of the two Mills is the person they both kept returning to for guidance and inspiration throughout their lives: Plato. (shrink)

Against the standard reading of Isaiah Berlin's thought that drives a wedge between his early and subsequent work, this article suggests that his late normative anti-reductionism has roots in the early writings on meaning, semantics and truth. Berlin's anti-reductionist objection to logical positivists in the realm of semantics evince a sensitivity to reductionism, a recognition of the irreducibility of propositional meaning, a plea for the embededness of language in a temporal continuum, an anti-dualist call, and a celebration of the plural (...) and open-ended character of propositions, all of which keep broad affinity with his mature value pluralism in ethics and politics. The unity of concerns in Berlin's work brings about two implications. First, it sheds light on the fact that Berlin's ethical and political pluralism rests on views about semantics and ontology as well. Second, it offers a basis on which to deflect some current moral realist readings of his value pluralism, offering instead a history-laden understanding of his pluralism that provides more compelling grounds to understand the relationship between the latter and liberalism in Berlin's work. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:82 HISTORY OF PHILOSOPHY PEIRGE'S MARGINALIA IN W. T. HARRIS' Hegel's Logic Among the most eminent philosophers of nineteenth-century America were William Torrey Harris (1835-1909) and Charles Sanders Peirce (18391914 ). The former, by his establishment in 1867 of The Journal of Speculative Philosophy, furnished a starting point for American philosophical maturity. The latter, who contributed to that iournal, has been considered America's greatest logician. It may therefore be (...) of interest to examine Peirce's marginalia in the first edition of Harris' chief work, Hegel's Logic: A Book on the Genesis of the Categories of the Mind (Chicago: S. C. Griggs, 1890). Discovered by the present writer on a New York book-stall, in a cheaply priced, coverless, and water-stained copy, and now in his possession, it bears imprinted on the reverse of the title page: "Harvard University: Philos. Dept. Library. Gift of Mrs. Charles S. Peirce. June 28, 1915." Shortly after Peirce, in depressed circumstances, died on April 19, 1914, the Harvard Philosophy Department acquired from his wife the manuscripts that were published in the Collected Papers.1 Harris' Hegel's Logic, which presumably accompanied that transaction, contains several marginal annotations, mostly in faded ink, in a neat, small hand, similar to that reproduced in the frontispiece to Volume IV of Peirce's Collected Papers. Recalling a notable philosophical conjunction, the markings also reveal aspects of Peirce's character and confirm his complex attitude toward Hegel, crucial to the development of his philosophy. Peirce's shifting view and persistent concern regarding Hegel may be traced in some other remarks. For example, in a letter to Harris dated January 1, 1868, he says, "I admit there is music in the logic of Hegel, but that is all I discover there. ''2 In another letter to Harris, dated May 13, 1868, he indicates his ambivalence: "But as I should draw the line... I should come on the same side as Hegel, because I am idealistic. I do not 1eel very much opposed to Hegel, though I think his main point.s tin his own estimate of importance) are wrong. ''s About 1890, Peirce declared, "I reiect his philosophy in toto, ''~ and about 1896, he accused Hegel of reaching "each category from the last preceding by virtually calling 'next!'-5 Yet, in 1903, he acclaimed Hegel "in some respects the greatest philosopher that ever lived. ''6 And, in the very same year, reviewing another treatment of Hegel's logic, and including a reference to Harris' t Eds. Charles Hartshorne, Paul Weiss,and Arthur Burks (Vols.I-VIII; Cambridge: Harvard University Press, 1958). 2,.C.S. Peirce to W. T. Harris." ed. WallaceNethery, The Personalist,XLIII (19fi2),37. I am indebted to Dr. Nethery for his kindness in letting me see these letters in advanceof publication. sIbid.,40. 4Collected Papers,I, 193. 5 Ibid., I, 246. eIbid., I, 277. NOTES AND DISCUSSIONS 83 treatise, Peirce flatly remarks: "But all these Hegelians--Harris, XVallace, Hibben, Everett, etc.--who dog the steps of their master in almost textual comments, are profoundly unfaithful to the spirit of his philosophy... the Logik now condemns itself. ''7 A constant feature in Peirce's negative attitude toward Hegel concerns the latter's failure to equip himself scientifically to deal with a subject the American considered basically scientific. For instance, about 1899, Peirce writes: Hegel, while regarding scientific men with disdain, has for his chief topic the importance of continuity, which was the very idea the mathematicians and physicists had been chiefly engaged in following out for three centuries. This made Hegel's work less correct and excellent in itself than it might have been; and at the same time hid its true mode of affinity with the scientific thought into which the life of the race had been chiefly laid up. It was a misfortune for Hegelism~ a misfortune for "philosophy," and a misfortune (in lesser degree) for science: Although Peirce adds, "My philosophy resuscitates Hegel, though in a strange costume, ''9 and his dialectic parallels Hegel's, he attempts to escape the Hegelian subjectivism by an "objective logic" and by avoiding Hegel's supposed mathematical ignorance. "Most of what is true in... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:82 HISTORY OF PHILOSOPHY PEIRGE'S MARGINALIA IN W. T. HARRIS' Hegel's Logic Among the most eminent philosophers of nineteenth-century America were William Torrey Harris (1835-1909) and Charles Sanders Peirce (18391914 ). The former, by his establishment in 1867 of The Journal of Speculative Philosophy, furnished a starting point for American philosophical maturity. The latter, who contributed to that iournal, has been considered America's greatest logician. It may therefore be (...) of interest to examine Peirce's marginalia in the first edition of Harris' chief work, Hegel's Logic: A Book on the Genesis of the Categories of the Mind (Chicago: S. C. Griggs, 1890). Discovered by the present writer on a New York book-stall, in a cheaply priced, coverless, and water-stained copy, and now in his possession, it bears imprinted on the reverse of the title page: "Harvard University: Philos. Dept. Library. Gift of Mrs. Charles S. Peirce. June 28, 1915." Shortly after Peirce, in depressed circumstances, died on April 19, 1914, the Harvard Philosophy Department acquired from his wife the manuscripts that were published in the Collected Papers.1 Harris' Hegel's Logic, which presumably accompanied that transaction, contains several marginal annotations, mostly in faded ink, in a neat, small hand, similar to that reproduced in the frontispiece to Volume IV of Peirce's Collected Papers. Recalling a notable philosophical conjunction, the markings also reveal aspects of Peirce's character and confirm his complex attitude toward Hegel, crucial to the development of his philosophy. Peirce's shifting view and persistent concern regarding Hegel may be traced in some other remarks. For example, in a letter to Harris dated January 1, 1868, he says, "I admit there is music in the logic of Hegel, but that is all I discover there. ''2 In another letter to Harris, dated May 13, 1868, he indicates his ambivalence: "But as I should draw the line... I should come on the same side as Hegel, because I am idealistic. I do not 1eel very much opposed to Hegel, though I think his main point.s tin his own estimate of importance) are wrong. ''s About 1890, Peirce declared, "I reiect his philosophy in toto, ''~ and about 1896, he accused Hegel of reaching "each category from the last preceding by virtually calling 'next!'-5 Yet, in 1903, he acclaimed Hegel "in some respects the greatest philosopher that ever lived. ''6 And, in the very same year, reviewing another treatment of Hegel's logic, and including a reference to Harris' t Eds. Charles Hartshorne, Paul Weiss,and Arthur Burks (Vols.I-VIII; Cambridge: Harvard University Press, 1958). 2,.C.S. Peirce to W. T. Harris." ed. WallaceNethery, The Personalist,XLIII (19fi2),37. I am indebted to Dr. Nethery for his kindness in letting me see these letters in advanceof publication. sIbid.,40. 4Collected Papers,I, 193. 5 Ibid., I, 246. eIbid., I, 277. NOTES AND DISCUSSIONS 83 treatise, Peirce flatly remarks: "But all these Hegelians--Harris, XVallace, Hibben, Everett, etc.--who dog the steps of their master in almost textual comments, are profoundly unfaithful to the spirit of his philosophy... the Logik now condemns itself. ''7 A constant feature in Peirce's negative attitude toward Hegel concerns the latter's failure to equip himself scientifically to deal with a subject the American considered basically scientific. For instance, about 1899, Peirce writes: Hegel, while regarding scientific men with disdain, has for his chief topic the importance of continuity, which was the very idea the mathematicians and physicists had been chiefly engaged in following out for three centuries. This made Hegel's work less correct and excellent in itself than it might have been; and at the same time hid its true mode of affinity with the scientific thought into which the life of the race had been chiefly laid up. It was a misfortune for Hegelism~ a misfortune for "philosophy," and a misfortune (in lesser degree) for science: Although Peirce adds, "My philosophy resuscitates Hegel, though in a strange costume, ''9 and his dialectic parallels Hegel's, he attempts to escape the Hegelian subjectivism by an "objective logic" and by avoiding Hegel's supposed mathematical ignorance. "Most of what is true in... (shrink)

Kleinschmidt's definition of the “Weltformenkreis” as the smallest systematical unit of affinity removes any danger of obliterating the type and at the same time opens a way for judging the superior taxonomic groups on principle differently from the subspecies of a “Formenkreis”.It is demonstrated that the characters of geographical subspecies are characters of apparent shaping, those of the species however are characters of construction and qualitative and autonomic ones. It is the type differentiating in quality that justifies the definition (...) of species. As the characters of type do not necessarily appear gradual and quantitative, but are qualitative, the types cannot be derived from one another, unless they are conceived by the common superordinate idea of the superior systematical category next in order.The distinct division of species is opposed to the hypothetical continuity of the pedigree, which cannot be explained by a consanguinity nor by an affinity based on reproduction. The pedigree, however, is an expression of the spiritual order of nature, in which the types appear as units hierarchically graduated and determined by entelechy, not by dead matter.Within the systematical units there is a creative evolution, steadily pursuing its aim and leading from the primitive stage to the differentiated one, beginning with a juvenile phase, which is followed by orthogenetic maturity and, finally, by the aged stage with its “detypification”. The adaptation to the environment may be also proved for the primitive forms and is an organic part of the whole design of the world for them as well as for the specialized and differentiated forms. — The formation of new types cannot be explained in a merely mechanical way; everywhere, even in the gens and genoms, we state ingenious modifications, which do not only bring about a reaction of a single modification to the whole, but operate from the whole. Since the origin of man, since the tertiary formation, the creation of species has completely ceased. There are only alterations of subspecific character.After a digressive treatise on the fundamental difference of man and animal in order to explain the type the superior systematical categories are characterized as spiritual realities. It is especially for the “genus” that a revision is necessary. The reality of the common origin of certain species within the genus is not based on reproduction , but on the superior totality comprising the species. Individuals can be conceived by the character of the species, species by the character of genus only. This is an evidence for the methodicalness of creative nature. It excludes any evolution of the genus “from bottom to top”, which is irregular, accidental or immediately formed by environment. From this we derive the comprehensive right of a natural system which now is more than mere classification.Kleinschmidt qui donne une définition du „Weltformenkreis” comme la plus petite unité d'affinité systématique, déjoue le danger d'oblitérer le type et offre, en même temps, la possibilité de juger les groupes taxonomiques supérieurs par principe différemment de la souspèce d'un „Formenkreis”.Nous démontrons que les caractères des souspèces géographiques sont des caractères du façonnement extérieur, tandis que ceux de l'espèce sont des caractères de la construction d'une manière qualitative et autonome. Le type différent en qualité justifie seulement la définition de l'espèce. Comme les caractères du type n'apparaissent pas nécessairement graduels et quantitatifs, mais sont au contraire, qualitatifs, les types ne se dérivent pas l'un de l'autre, à moins qu'ils ne soient compris par la commune idée supérieure du plus sublime groupe systématique.La division distincte des espèces s'oppose à la continuité hypothétique de la généalogie, qui ne s'explique pas par une consanguinité ni par une affinité se fondant sur la reproduction, mais qui est plutôt une expression du régime spirituel de la nature, dans lequel les types se présentent comme des unités rangées hiérarchiquement et réglées par l'entéléchie et non par la matière.Dans les unités systématiques il y a une évolution créatrice qui tend continuellement à son but et mène de la phase primitive à la phase différentiée commençant par un état juvénile, qui est succédé par la maturité orthogénétique et enfin par l'âge avec sa „détypification”. L'adaptation au milieu est démontrée pour les formes primitives et représente un élément organique du grand projet mondial pour elles aussi bien que pour les formes spécialisées et différentiées. — La formation de types nouveaux ne s'explique pas seulement d'une manière mécanique; partout, même dans les „genes” et les „genomes”, nous observons des transformations ingénieuses, qui ne sont pas seulement une réaction d'une modification particulière à l'ensemble, mais un effet de l'ensemble. Depuis l'origine de l'homme, depuis la période tertiaire la formation d'espèces est complètement finie. À présent il n'y a plus que des variations d'un caractère souspécifique. Après un traité digressif sur la différence essentielle de l'homme et de l'animal pour expliquer le type les groupes systématiques supérieurs sont caractérisés comme des réalités spirituelles. C'est surtout pour le genre qu'une révision est nécessaire. La réalité de la racine commune de certaines espèces dans le genre ne se fonde pas sur la reproduction , mais sur la totalité supérieure qui implique toutes les espèces. Des individus sont compris par le caractère d'espèce, des espèces seulement par le caractère de genre. C'est une preuve de la méthode de la nature créatrice. Elle exclut une évolution de genre „du bas en haut”, qui est irrégulière, faite par hasard ou formée directement par le milieu. De là nous dérivons le droit compréhensible d'un système naturel, qui est désormais plus qu'une simple classification. (shrink)

Epistemological issues are usually taken to be David Hume's central preoccupation. Attending to the role of sympathy in Hume's thought reveals, however, that his primary aim is to secure the conditions for social peace and prosperity in 18th-century Scotland and beyond, a peace particularly threatened by religious conflict. This perspective not only discloses the unity of Hume's ethical, political, aesthetic, and historical writings, it also suggests that the driving forces in the development of modern ethical and religious thought are ethical (...) and social rather than epistemological. ;The first two chapters discuss the background to Hume's use of sympathy and explore its application in the Treatise. In Hume's secularized account of moral approbation, sympathy fills the place Hutcheson reserved for Providence; it assures an intelligible connection between moral judgments and human flourishing in society. Hume at first makes use of a passive notion of sympathy developed by Latitudinarian divines to counter Hobbesian accounts of self-interested human nature. But this passive form of sympathy is limited and variable, threatening to reinforce, rather than alleviate, religious zeal and sectarian conflict. Hume introduces a new form of corrected, 'extensive' sympathy which involves an active effort to overcome prior affinities and cross factional boundaries. ;Appreciating the role of sympathy in morals also illuminates malfunctions of judgment among religious believers. Chapter 3 interprets Hume's essay on the pleasures of tragedy as an unmasking of Scottish Evangelical condemnation of theater. Evangelical opposition reflects pathologies of belief which grow out of a rejection of worldly existence and eventually distort sympathetic capacities. In "Of the Standard of Taste," discussed in Chapter 4, Hume grapples with disagreement in taste and judgment and argues that sympathy cannot be extended to those who live "artificial" religious lives, deducing practical consequences from speculative theories. ;Where poetry fails, however, history may succeed, since history is for Hume the paradigm of sympathetic understanding. As the final chapter argues, it is in the History of England that sympathy reaches its mature expression and Hume's delineation of the links among religious irrationality, zeal, and faction, attains its most concrete and persuasive form. (shrink)

This study contributes to the definition of populism as a significant current of thought in modern China through a focus on the development of the populist ideas of Liang Shuming . It provides an avenue to understanding a major thinker and social activist of modern China. At the same time, through a comparison with Russian Narodism, it develops populism as a general sociohistorical concept, denoting a constellation of ideas which emerges in a specific historical environment and includes a concern with (...) rural society and a critique of the modern West in the context of questions of the moral nature of progress. ;The dissertation describes the origins and development of Liang's ideas, presenting them against the background of major intellectual tendencies of the times. After an early urban, Westernizing focus, Liang arrived at a populist approach relatively late. A persisting habit of thought, involving a metaphor of mind, informed his early concerns, his attention to the ambiguities of progress and to the appeals of socialism, and his later foci on a critique of the West, an historical approach, and a particular concept of the psyche. The events of the 1920's provided the context in which Liang was able to reconcile his disparate concerns and develop a mature populist theory in which the villages provided a practical intersection of individual subjectivity and history. ;In the evolution of his ideas, Liang Shuming shared with other Chinese, Zhang Taiyan, Zhang Shizhao, Li Dazhao, and Mao Zedong, affinities which help define populism as a broad current of thought still important in China. A critique of the West and desire to skip over capitalism on the way to the future have more weight in Chinese populism than does a focus on rural society. In the absence of a specifically populist political movement, the historical importance of Chinese populism has derived from its interpenetration with Marxist ideas. One potential of the legacy of Chinese populism is to provide a self-conscious orientation toward the future from the perspective of a critique of both the Western present and the Chinese past. (shrink)

It is often alleged that liberalism and nationalism are mutually antagonistic in theory and practice. Max Weber is a good example, the dominant interpretation maintains, as his political thought betrays its liberal foundation by embracing an ardent nationalism that was popular in Wilhelmine Germany. Weber was, in short, a nationalist, and thus illiberal, political thinker. Against this conventional wisdom I argue that Weber's liberal nationalism cannot be placed squarely in the authoritarian, ethnic tradition of German nationalism, and its idiosyncrasy becomes (...) evident once Weber's twofold political project of revivifying a robust civil society while imbuing it with the spirit of public citizenship is foregrounded more clearly. Thus recast, Weber's political thought reveals a strong affinity with that of Tocqueville and Mill, especially in their similar concern with moral personality and political maturity in a mass democracy. (shrink)

This paper offers an exposition of Husserl's mature philosophy of mathematics, expounded for the first time in Logische Untersuchungen and maintained without any essential change throughout the rest of his life. It is shown that Husserl's views on mathematics were strongly influenced by Riemann, and had clear affinities with the much later Bourbaki school.

Kolakowski describes his massive and comprehensive study of Marxism as a "handbook." Following a classic pattern, he divides his study into three volumes, "The Founders," "The Golden Age," and "The Breakdown." Kolakowski does not claim to present a non-controversial account of the history of Marxism, however, his aim is "to include the principal facts that are likely to be of use to anyone seeking an introduction to the subject". The main organizing principle is chronological, although Kolakowski frequently departs from strict (...) chronology in order to deal with thinkers who share affinities in their approach to Marxism or to present background information about the historical context and alternatives to Marxism. The first volume begins with a discussion of the origins of dialectic that reaches back to the pre-Socratics carrying us through the neo-Platonic tradition to Kant, Fichte, and Hegel. This is followed by an analysis of the views of the left Hegelians and a detailed exposition of Marx, from his early to his mature writings. The volume concludes with a discussion of Engels’s understanding of the dialectics of nature. Volume 2 begins with an analysis of Marxism and the Second International. There are separate chapters on Karl Kautsky, Rosa Luxemburg, Eduard Bernstein, Jean Jaurès, Paul Lafargue, Georges Sorel, Antonio Labriola, Ludwik Krzywicki, Kasimierz Kelles-Krauz, Stanislaw Brzozowski, and the Austro-Marxists. Kolakowski then treats in detail the origins of Russian Marxism culminating in a discussion of Leninism and its fortunes. The final volume follows the bleak story of Soviet Marxism, but also treats the alternatives to Soviet ideology with chapters on Antonio Gramsci, György Lukács, Karl Korsch, Lucien Goldmann, the Frankfurt School, Herbert Marcuse, and Ernst Bloch. There is a final chapter that surveys developments in Marxism since Stalin’s death. The main emphasis is on European Marxism although there is a brief discussion of the peasant Marxism of Mao-Tse-tung. The erudition, the mastery of detail, and the scope exhibited is remarkable. There is nothing comparable to this work in English. The style is so lucid and the translation so good that it is difficult to believe that the study was not originally written in English. Both the novice and the advanced scholar can learn from these volumes. But the study is not really an introduction. Kolakowski’s expositions, interpretations, and criticisms are at once highly sophisticated and highly controversial. It is a handbook that needs to be used with caution despite Kolakowski’s claim that he had done his best "not to merge comment with exposition, but to present my own views in separate, clearly defined sections". (shrink)

Agriculture has been recently viewed as the primary destructive force of biodiversity, but the places that produce our food and fiber may also hold the key to saving the richness of life on earth. This argument is based on three fundamental positions. First, it is argued that to value and thereby preserve and restore biodiversity we must begin by employing anthropocentric ethics. While changing our understanding of intrinsic values (i.e., the unconditional values of biodiversity as a state and process in-and-of-itself, (...) without reference to human interests) is often advocated as the means by which our behavior will reflect the importance of biodiversity, a change in how we perceive and conditionally value biodiversity is proposed as a more effective and compelling approach. Second, I suggest that anthropocentric values can be linked to a sense of “Place,” with agriculture playing a vital role in this context. Agriculture forms a powerful basis for personal, experiential development of a profound meaning and connection to a setting or landscape. The agricultural setting has tremendous potential for arational (emotional, aesthetic, and spiritual) values that ultimately compel our actions. The constancy of relationship and mutuality of dependency between humans and agricultural lands, particularly extensive agroecosystems, fosters an intensity of association that transcends our recent affinity to wildlands. Third, a mature understanding of places and their biodiversity must include those organisms that account for many of the ecological processes and the majority of the species richness -- the insects. The importance of these insects in structuring the landscape and the effects of habitat destruction on these organisms both suggest a vital, intimate, and reciprocal link between insects and Places. Finally, it is argued that the most important avenue for future efforts to protect and restore biodiversity on the part of agricultural and other scientists is educational -- the presentation of our research to the public in terms that provoke emotional, aesthetic, and spiritual meaning which lies at the core of human values and actions. (shrink)

Due to COVID-19, the fragile economy, travel restrictions, and generalized anxieties, the concept of antibodies as a “declaration of immunity” or “passport” is sweeping the world. Numerous scientific and ethical issues confound the concept of an antibody passport; nonetheless, antibodies can be seen as a potential currency to allow movement of people and resuscitation of global economics. Just as financial currency can be forged, so too is the potential for fraudulent antibody passports. This paper explores matters of science, (...) ethics, and identity theft, as well as the problems of bias and discrimination that could promulgate a world of pandemic “golden passports.”. (shrink)

The immunoglobulin molecule is a perfect template for the de novo generation of biocatalytic functions. Catalytic antibodies, or abzymes, obtained by the structural mimicking of enzyme active sites have been shown to catalyze numerous chemical reactions. Natural enzyme analogs for some of these reactions have not yet been found or possibly do not exist at all. Nowadays, the dramatic breakthrough in antibody engineering and expression technologies has promoted a considerable expansion of immunoglobulin's medical applications and is offering abzymes a (...) unique chance to become a promising source of high‐precision “catalytic vaccines.” At the same time, the discovery of natural abzymes on the background of autoimmune disease revealed their beneficial and pathogenic roles in the disease progression. Thus, the conflicting Dr. Jekyll and Mr. Hyde protective and destructive essences of catalytic antibodies should be carefully considered in the development of therapeutic abzyme applications. (shrink)

Protection against bacterial and viral pathogens by antibodies has always been thought to end at the cell surface. Once inside the cell, a pathogen was understood to be safe from humoral immunity. However, it has now been found that antibodies can routinely enter cells attached to viral particles and mediate an intracellular immune response. Antibody‐coated virions are detected inside the cell by means of an intracellular antibody receptor, TRIM21, which directs their degradation by recruitment of the ubiquitin‐proteasome system. (...) In this article we assess how this discovery alters our view of the way in which antibodies neutralise viral infection. We also consider the antiviral function of TRIM21 in the context of its other reported roles in immune signalling and autoimmunity. Finally, we discuss the conceptual implications of intracellular antibody immunity and how it alters our view of the discrete separation of extracellular and intracellular environments. (shrink)

Since the realisation that the antigen‐binding regions of antibodies, the variable (V) regions, can be uncoupled from the rest of the molecule to create fragments that recognise and abrogate particular protein functions in cells, the use of antibody fragments inside cells has become an important tool in bioscience. Diverse libraries of antibody fragments plus in vivo screening can be used to isolate single chain variable fragments comprising VH and VL segments or single V‐region domains. Some of these are (...) interfering antibody fragments that compete with protein‐protein interactions, providing lead molecules for drug interactions that until now have been considered difficult or undruggable. It may be possible to deliver or express antibody fragments in target cells as macrodrugs per se. In future incarnations of intracellular antibodies, however, the structural information of the interaction interface of target and antibody fragment should facilitate development of binding site mimics as small drug‐like molecules. This is a new dawn for intracellular antibody fragments both as macrodrugs and as precursors of drugs to treat human diseases and should finally lead to the removal of the epithet of the ‘undruggable’ protein‐protein interactions. (shrink)

Central to vaccination-induced responses, antibodies are suggested by Vaz to operate as observer-dependent entities that owe their status to categorization schemes of immunologists. Inspired by color research by Maturana, he argues that antibodies should be distinguished from immunoglobulins, which unlike the former can be considered as constituents of structural dynamics of an organism, products of millions of years of evolution. However, a deeper understanding of the historical roots of the concept of immunoglobulin and associated “languaging” and naming processes reveals that (...) immunoglobulins, as much as antibodies, are contingent on conceptual schemes of immunology. (shrink)

Antibodies that are specific for DNA provide an excellent system for studying the protein‐nucleic acid interactions that allow proteins to recognize specific DNA structures or sequences.

This paper aims to measure Knowledge Management Maturity (KMM) in the universities to determine the impact of knowledge management on high performance. This study was applied on Al-Quds Open University in Gaza strip, Palestine. Asian productivity organization model was applied to measure KMM. Second dimension which assess high performance was developed by the authors. The controlled sample was (306). Several statistical tools were used for data analysis and hypotheses testing, including reliability Correlation using Cronbach’s alpha, “ANOVA”, Simple Linear Regression and (...) Step Wise Regression.The overall findings of the current study suggest that KMM is suitable for measuring high performance. KMM assessment shows that maturity level is in level three. Findings also support the main hypothesis and it is sub- hypotheses. The most important factors effecting high performance are: Processes, KM leadership, People, KM Outcomes and Learning and Innovation. Furthermore the current study is unique by the virtue of its nature, scope and way of implied investigation, as it is the first comparative study in the universities of Palestine explores the status of KMM using the Asian productivity Model. (shrink)

Monoclonal antibodies are essential biomedical research and clinical reagents that are produced by companies and research laboratories. The NIAID ImmPort (Immunology Database and Analysis Portal) resource provides a long-term, sustainable data warehouse for immunological data generated by NIAID, DAIT and DMID funded investigators for data archiving and re-use. A variety of immunological data is generated using techniques that rely upon monoclonal antibody reagents, including flow cytometry, immunofluorescence, and ELISA. In order to facilitate querying, integration, and reuse of data, standardized (...) terminology for describing monoclonal antibody reagents and their targets needs to be used for annotating data submitted to ImmPort. (shrink)

Elective Affinities: Musical Essays on the History of Aesthetic Theory collects a selection of Lydia Goehr's recent essays. In them she traces “a history of attraction and reaction … of music to philosophy, drama, birdsong, crime, film, and nationhood” . Goehr examines the ways that philosophers, the ideas that they present, and works of art display “elective affinities”. Her procedure is like that of an art historian who presents parallel slides to reveal visual affinities, even between artists who themselves were (...) unaware of each other. Her analyses are erudite, lucid, and always suggestive, but what I found most admirable in Elective Affinities is Goehr's extraordinarily brave experimentation with a novel form of philosophy-writing, the adumbration of which is the focus of this review. Her book is strange enough to be genuinely magnificent and lastingly influential. (shrink)