Peter Adamson

Protein Tyrosine Kinase Inhibitors Act Downstream of IL-1α and LPS Stimulated MAP-Kinase Phosphorylation to Inhibit Expression of E-Selectin on Human Umbilical Vein Endothelial Cells

HUVEC exposed to IL-1α, TNFα or LPS showed a time dependent increase in E-selectin expression which was maximal at between 4-6h after stimulation. Stimulation of HUVEC with IL-1α, TNFα or LPS for between 2 and 6h followed by removal or neutralisation of IL-la, TNFα or LPS and incubation in new media up to 6h resulted in identical levels of E-selectin expression at 6h, as cells which had been continuously stimulated for 6h with IL-1α, TNFα or LPS. These studies demonstrated that HUVEC were committed to the induction of E-selectin following a 2 hr incubation with either IL-1α, TNFα or LPS. The protein tyrosine kinase (PTK) inhibitors ST271, ST638 or genistein (0-100M) were ineffective in reducing cytokine or LPS stimulated E-selectin expression during a 2h cytokine or LPS stimulation of cells, in which inhibitors were either coincubated with cytokine/LPS or previously preincubated with the PTK inhibitors.However when PTK inhibitors were present during both agonist activation (2h) and subsequent expression o...

Avicenna and the Avicennian Tradition

The scope of this chapter is dauntingly broad, since Avicenna was the central figure in the history of Arabic-Islamic philosophy. Before Avicenna, falsafa (Arabic Aristotelian and Neoplatonic philosophy) and kalām (Islamic doctrinal theology) were distinct strands of thought, even though a good deal of cross-fertilization took place between them. After Avicenna, by contrast, the two strands fused together and post-Avicennian kalām emerged as a truly Islamic philosophy, a synthesis of Avicenna’s metaphysics and Muslim doctrine. To talk about the sources, evolution, and influence of Avicenna’s ideas is, in fact, to talk about over two thousand years of philosophical activity. Avicenna’s sources begin with Aristotle in the fourth century B.C.E. and include the late antique Greek Aristotle commentators, both Peripatetic and Neoplatonist. Avicenna himself was extremely prolific: between 40 and 275 titles have been attributed to him by bibliographers ranging from his student Jūzjānī to the late Egyptian scholar Georges Anawati, with approximately 130 reckoned to be authentic by the Iranian scholar Yahyā Mahdavī. What is more, his ideas evolved during the course of his career,with the result that, as with Plato’s and Aristotle’s thought, Avicenna’s philosophy will often resist our attempts to systematize it, and his position on a number of important philosophical issues will appear frustratingly underdetermined. As for Avicenna’s impact, it was felt acutely in both the Islamic world and in Christian Europe.

Al-Kindi and the Mu‘tazila: Divine Attributes, Creation and Freedom

The paper discusses al-Kindis response to doctrines held by contemporary theologians of the Mu‘tazilite school: divine attributes, creation, and freedom. In the first section it is argued that, despite his broadly negative theology, al-Kindi recognizes a special kind of “essential” positive attribute belonging to God. The second section argues that al-Kindi agreed with the Mu‘tazila in holding that something may not yet exist but still be an object of Gods knowledge and power (as the Mu‘tazila put it, that “non-being” is a “thing”). Also it presents a new parallel between al-Kindi and John Philoponus. The third section gives an interpretation of al-Kindi as a compatibilist, in other words as holding that humans may be free even though their actions are necessitated. In all three cases, it is argued, al-Kindi is close to the Mu‘tazilite point of view, though he departs from them in the arguments he gives for that point of view.

[19] Microinjection of epitope-tagged Rho family cDNAs and analysis by immunolabeling

Publisher Summary This chapter describes the way in which microinjection of expression vectors coding for epitope-tagged proteins can be used to analyze the intracellular localization of Rho family proteins. Analysis of the intracellular distribution of small GTP-binding proteins in both normal and mutant forms can convey useful information regarding the function of these molecules. In particular, immunolabeling of these proteins in situ can give a more precise indication of their location within the cell than is obtainable by cell fractionation techniques. The conventional approach is to raise antibodies against each protein or against synthetic peptides derived from an amino acid sequence. However, producing antibodies against proteins of the Ras superfamily is complicated by the high-sequence homology that typifies this group of molecules. The most widely used are peptides derived from influenza hemagglutinin, vesicular stomatitis virus (VSV) G protein, and human c- myc , although in principle, any peptide corresponding to the epitope recognized by an existing antibody is a suitable candidate. The most important attributes of an antibody are (1) it should not show affinity for endogenous cellular proteins and (2) it should bind with high affinity to the epitope tag even after the rigors of cell fixation.

Before Essence and Existence: al-Kindi's Conception of Being

IN THE PERSON OF AL-KIND¥ (died ca. 870 A.D.), the Arabic tradition had its first selfconsciously “philosophical” thinker. Those familiar with al-Kind¥ may know him chiefly because of his role in the transmission of Greek philosophy, though it is his transformation of the ideas he inherited that will interest us most here. While it is not clear whether al-Kind¥ himself could read Greek,1 it is well documented that he guided the efforts of several important early translators. These included Us· tāth, translator of Aristotle’s Metaphysics; Ya · hyā b. al-Bi· tr¥q, who paraphrased several Platonic dialogues as well as translated Aristotle’s De Caelo; and Ibn Nā’ima al· Him· s¥. Al· Him· s¥ translated logical works of Aristotle and parts of the Enneads of Plotinus, the latter in a paraphrase that has come down to us as a group of three texts dominated by the so-called Theology of Aristotle.2 (I will refer below to these three texts collectively as the Arabic Plotinus.) Al-Kind¥’s circle of translators also produced a similar paraphrase of Proclus’s Elements of Theology, which went first by the name Book on the Pure Good in its Arabic version and later, in its Latin version, by the title Liber de Causis. Translations in the Baghdad circle were made from both Greek and Syriac, and were supported by the ‘Abbāsid caliphs al-Ma’mūn

Miskawayh on Pleasure

This paper provides an analysis and translation of a previously edited, but otherwise unstudied work by Miskawayh (d. 1030) entitled On Pleasures and Pains ( Fī al-Laḏḏāt wa-al-ālām ). After a brief orientation regarding the Aristotelian account of pleasure in the Nicomachean Ethics , which is Miskawayhs main source, the theory of pleasure set out in On Pleasures and Pains is compared to the discussion of pleasure in Miskawayhs better known Refinement of Character ( Tahḏīb al-aḫlāq ). Despite considerable harmony between the two texts, their treatments of pleasure differ in that the Refinement accepts, whereas On Pleasures and Pains rejects, the “restoration” theory of pleasure of Platos Timaeus .

Abū Bakr al-Rāzī on Animals

Abstract: Abū Bakr al-Rāzī (d. 925), a doctor known not only for his medical expertise but also for his notorious philosophical ideas, has not yet been given due credit for his ideas on the ethical treatment of animals. This paper explores the philosophical and theological background of his remarks on animal welfare, arguing that al-Rāzī did not (as has been claimed) see animals as possessing rational, intellectual souls like those of humans. It is also argued that al-Rāzī probably did not, as is usually believed, endorse human-animal transmigration. His ethical stance does not in any case depend on shared characteristics of humans and animals, but rather on the need to imitate God’s providence and mercy.

The Arabic Sea Battle: al-Fārābī on the Problem of Future Contingents

Abstract Ancient commentators like Ammonius and Boethius tried to solve Aristotles “sea battle argument” in On Interpretation 9 by saying that statements about future contingents are “indefinitely” true or false. They were followed by al-Fārābī in his commentary on On Interpretation. The article sets out two possible interpretations of what “indefinitely” means here, and shows that al-Fārābī actually has both conceptions: one applied in his interpretation of Aristotle, and another that he is forced into by the problem of divine foreknowledge. It also explains the relevance of al-Fārābīs remarks as a link between the non-statistical modal theories of Philo and Avicenna.

Induction of E-Selectin by Endotoxin is Direct and not Mediated Through Intracellular or Extracellular Release of Secondary Cytokines

Using a fixed cell ELISA system E-selectin expression and adhesion of U937 cells were measured in both endotoxin (LPS: serotype 0111:B4) tregted and untreated cultures of human umbilical vein endothelial cells (HUVEC). Basal levels of E-selectin were unde-tectable whereas significant induction of both E-selectin and U937 cell adhesion were observed after exposure of HUVEC to LPS for 6h. The effect of LPS was serum dependent and unaffected by coincubation with neutralising antibodies to either IL-1α, IL-1β or TNFα either alone or in combination, even though each antibody was capable of neutralising the effect of exogenously added cytokine. In addition IgG fractions of neutralising anti-cytokine antibodies were purified, concentrated and microinjected into the cytosol of adherent HUVEC prior to treatment with 1 μg/ml LPS for 6 hrs. Immunofluorescence staining showed that cells microinjected with antibodies to IL-1α, IL-1β and TNFα either alone or in combination were positive for LPS-stimulated E-selectin, d...

FAKHR AL-DĪN AL-RĀZĪ ON PLACE

The twelfth century philosopher-theologian Fakhr al-Din al-Razi is well known for his critique of Lambda vicennan metaphysics. In this paper, I examine his critique of Avicennas physics, and in particular his rejection of the Lambda vicennan and Aristotelian theory of place as the inner boundary of a containing body. Instead, Fakhr al-Din defends a definition of place as self-subsisting extension, an idea explicitly rejected by Aristotle and Avicenna after him. Especially in his late work, the Matalib, Fakhr al-Din explores a number of important philosophical issues with reference to this theory of place, including the principle that two indiscernible things (in this case two overlapping extensions) must be identical and the idea that motion and rest are always relative.