Ras proteins function as critical relay switches that regulate diverse signaling pathways between cell surface receptors and the nucleus. Over the past 2‐3 years researchers have identified many components of these pathways that mediate Ras activation and effector function. Among these proteins are several guanine nucleotide exchange factors (GEFs), which are responsible for directly interacting with and activating Ras in response to extracellular stimuli. Analogous GEFs regulate Ras‐related proteins that serve other diverse cellular functions. In particular, a growing family of (...) proteins (Dbl homology proteins) has recently been identified, which may function as GEFs for the Rho family of Ras‐related proteins. This review summarizes our current knowledge of the structure, biochemistry and biology of Ras and Rho family GEFs. Additionally, we describe mechanisms of GEF activation of Ras in signal transduction and address the potential that deregulated GEFs might contribute to malignant transformation through chronic Ras protein activation. (shrink)

Afferent feedback can appreciably alter the pharyngeal phase of swallow. In order to measure the stability of the swallow motor pattern during several types of alterations in afferent feedback, we assessed swallow during a conventional water challenge in four anesthetized cats, and compared that to swallows induced by fixed (20 Hz) and stochastic (1-20Hz) electrical stimulation applied to the superior laryngeal nerve. The swallow motor patterns were evaluated by electromyographic activity (EMG) of eight muscles, based on their functional significance: laryngeal (...) elevators (mylohyoid, geniohyoid, and thyrohyoid); laryngeal adductor (thyroarytenoid); inferior pharyngeal constrictor (thyropharyngeus); upper esophageal sphincter (cricopharyngeus); and inspiratory activity (parasternal and costal diaphragm). Both the fixed and stochastic electrical stimulation paradigms increased activity of the laryngeal elevators, produced short-term facilitation evidenced by increasing swallow durations over the stimulus period, and conversely inhibited swallow-related diaphragm activity. Both the fixed and stochastic stimulus conditions also increased specific EMG amplitudes, which never occurred with the water challenges. Stochastic stimulation increased swallow excitability, as measured by an increase in the number of swallows produced. Consistent with our previous results, changes in the swallow motor pattern for pairs of muscles were only sometimes correlated with each other. We conclude that alterations in afferent feedback produced particular variations of the swallow motor pattern. We hypothesize that specific SLN feedback might modulate the swallow central pattern generator during aberrant feeding conditions (food/liquid entering the airway), which may protect the airway and serve as potentially important clinical diagnostic indicators. (shrink)

En el presente artículo se defiende la tesis de que existe un concepto globalizable de justicia a pesar de las diferencias culturales. Este concepto se basa en la igualdad con miras al establecimiento de un orden jurídico global democrático que garantice la administración de la justicia al interior de y entre los Estados. El artículo ofrece un marco conceptual de la posibilidad de dicho orden jurídico global democrático y de los retos y tareas a los cuales se enfrenta en su (...) pretensión de suministrar criterios sociales y de protección del medio ambiente para la puesta en marcha de una política de desarrollo global. (shrink)

Abrogation (naskh) is one of the controversial themes of Islamic studies, especially in later period that of principle of exegesis (uṣūl al-tafsīr). However, the recent studies on abrogation (naskh) do not offer a comprehensive analysis on the concept. In fact, the problem of naskh (abrogation) is in need of a systematic and holistic approach, which would only be possible with a detailed study on how the concept of abrogation (naskh) is understood in Islamic interpretive tradition (tafsīr). With this purpose in (...) mind, this article intends to examine two points regarding the term abrogation: first, the article will offer a analytical reflection on the diverse views of naskh, and then it will highlight how Ibn Kathīr (d. 1373) understood and applied this term to his hermeneutical framework. By doing so, the present study aims to show Ibn Kathīr’s position in Islamic interpretive tradition on the matter of naskh. The key conclusion of this study is that although Ibn Kathīr is one of the representatives of the traditional riwayah (sound transmission through a chain of exegetes) exegesis, he advances his interpretive hermeneutics with multiple aspects that also involves dirayah (personal opinion) exegesis (tafsīr). SUMMARY The problem of naskh (abrogation) is one of the most important and controversial themes of science and principle of exegesis (ʿilm wan a-l uṣūl al-tafsīr) in Islamic tradition. In order to understand naskh, which is claimed to be occurred in the Qur’ānic text, it is necessary to involve the time of the revelation of the Qur’ān. An analysis of this period reveals that first Muslims regard the naskh as a natural process of the revelation and do not dispute over this matter. In other words, the controversial theme naskh is perceived by first addresses of the Qur’ān as a hermeneutical characteristic of the Qur’ānic revelation. Therefore, naskh was not considered as a controversial concept and debated its origins based on the question whether it organically belonged to the revelation. It will be clear that the different views on naskh (abrogation), particularly after the time of the Companions is not a conceptual problem; rather Muslim scholars differed in their methodological approaches to naksh. Naskh has not been questioned as a concept in early Islamic tradition. Rather it has gradually developed over the centuries. Naskh has been elaborated with the terms of uṣūl al-fiqh (principles of Law), such as takhṣīṣ (specification) and taqyīd (restriction) and its conceptual meaning has been extended after, particularly Abū ʿAbdullah Muḥammad b. Idris b. ʿAbbas al-Shāfiʿī (d. 820). To sum up, naskh is regarded with a methodological perspective. However, in the field of Turkish Islamic studies, especially after the Cumhuriyet, the term naskh is not regarded as a natural consequence of the process of tanzīl (revelation of the Qur’ān) neglecting the gradual aspect of revelation and the disputes over the term has been concluded either rejecting or simply accepting this concept without providing a satisfactory result on the matter. This article examines one of the most prominent Muslim exegete Ibn Kathīr’s (d. 1373) approach to the problem of naskh in the context of previous modern scholarship on naskh (abrogation). However, the analysis of Ibn Kathīr’s perception of naskh does not claim to be exhaustive on the matter. This requires a more comprehensive study on the concept of naskh, which is clearly beyond the scope of this article. Therefore, the present study intends to specifically focus on general aspect of Ibn Kathīr’s understanding of naskh and how his perception is presented in modern studies. When Ibn Kathīr’s commentary is analysed, it becomes clear that his understanding of naskh is significant and not necessarily in line with his riwayah (sound transmission through a chain of exegetes) tafsīr (exegesis). For example, he notes the dates between abrogating and abrogated Qur’ānic verses and claims that it is necessary to find certain proofs to validate the claim of abrogation (naskh) for particular legal judgments and verses, which clearly shows that Ibn Kathīr approaches to the problem of naskh with a methodological perspective. Ibn Kathīr’s interpretation of the well known Qur’ānic verse Q 2.106 in a different sense and most importantly his consideration of the matter only in the Qur’ānic context are clear examples of his methodological approach. His interpretation of Q 2.106 simply shows that he meticulously distinguish between the acceptance of naskh as a concept and as an interpretive method. The modern studies on naskh, on the contrary, consider the matter only on the base of a conceptual analysis. Ibn Kathīr prefers to transmit the traditional opinions based on personal interpretation and interprets some Qur’ānic verses. This is clearly his method of re-interpretation based on rational thinking (taʾwīl). His way of rational reasoning leads Ibn Kathīr to the rejection of naskh (abrogation) and the restriction of Qur’ānic verses that are related to the theory of abrogating and abrogated verses (nāsikh-mansūkh). This clearly proves that Ibn Kathīr does not merely adopts and employs the method of riwayah, which is contrary to the supposition that he is the exegete of a commentary that heavily draws on hadith reports and transmitted traditional reports. In fact, this most importantly shows that Ibn Kathīr’s Qur’ān commentary can also be regarded as a dirayah (personal opinion) tafsīr (exegesis) and that there are enough material in traditional Muslim Qur’ānic exegesis to re-analyse the problem of naskh (abrogation). Relying on this last point, this article argues that a comprehensive analysis of naskh requires a research on the traditional interpretive sources. Therefore, it might be helpful to reconsider the matter of naskh with its conceptual background in the works of traditional Muslim exegetes rather than focusing only on whether the concept naskh exits or not in the origins of the Qur’ānic revelation. At this point, an analysis of Ibn Kathīr’s perception of naskh and his rational reasoning that is employed in his commentary will contribute to the understanding of the theory of naskh (abrogation) in the tradition of Qur’ānic exegesis. (shrink)

The ‘four famous cruces’ of this satire are as interesting as notorious. I regard the first as solved, since I cannot imagine anybody improving upon Postgate's line 13 . But I find instead a hitherto undetected but quite palpable flaw in the opening words.

1. Escritos doctrinales -- 2. Escritos histórico-filosóficos.

The current SARS-CoV-2 pandemic has killed thousands across the world. SARS-CoV-2 is the latest but surely not the last such global pandemic we will face. The biomedical response to such pandemics includes treatment, vaccination, and so on. In this paper, though, we argue that it is time to consider an additional strategy: the somatic (non-heritable) enhancement of human immunity. We argue for this approach and consider bioethics objections we believe can be overcome.

Although increasing in usage, surrogacy remains the most controversial method of assisted reproductive technology. Many Christian ethicists have either objected tout court or expressed strong reservations about the practice. Behind much of this caution, however, lies essentialist assumptions about pregnant women or an overemphasis on the statistical minority of well-publicized disasters. The question remains whether Christian ethical reflection on surrogacy might change if informed by social scientific studies on the surrogacy triad. I offer a feminist Christian framework for surrogacy comprised (...) of seven principles drawn from this literature, the reproductive justice paradigm, human rights, and Reformed theo-ethical norms. I ultimately advance surrogacy under certain conditions as a moral good and focus on “altruistic” arrangements—including my own—without concluding that only non-commercial contracts could pass ethical muster. (shrink)

El artículo explora las relaciones entre el derecho, la democracia y el imperativo del trato igual, deteniéndose en el desarrollo de nociones como “comunidad política”, “actos políticos” o “derechos”, y proponiendo un entendimiento específico de los “derechos democráticos” en cuyo contexto el derecho de igual acceso a la protección judicial juega un papel crucial. El análisis combina exploraciones en el plano del lenguaje jurídico dogmático con acometidas filosóficas, filológicas, históricas y sociopolíticas, en consonancia con la idea de que las fuentes (...) históricas son las coordenadas que rodean la experiencia jurídica y el juego democrático. (shrink)

The human Y chromosome contains very low levels of nucleotide variation. It has been variously hypothesized that this invariance reflects historic reductions in the human male population, a very recent common ancestry, a slow rate of molecular evolution, an inability to evolve adaptively, or frequent selective sweeps acting on genes borne on the Y chromosome. We propose an alternative theory in which human Y chromosome evolution is driven by mutations in the maternally inherited mitochondrial genome, which impair male fertility and (...) ultimately lead to a reduction in the effective population size (Ne) and consequently the variability of the Y chromosome. BioEssays 24:275–279, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10062. (shrink)

In his paper ‘On what there’s not’, Joseph Melia disavows commitment to the existence of objects like average mothers, possibilities, numbers, etc. Since quantification over such objects is at times unavoidable, Melia tries to argue that we can deny the existence of such objects despite the fact that our (true) theories of the world quantify over them. Melia calls this ‘weaseling’. In this paper, I argue that these assumptions of Melia’s render his position incoherent.

On οδ γγελός τίς κτλ. Jebb writes: ‘The sentence begins as if γγελός were to be followed by λθε:but the second alternative, συμπράκτωρ όδοû suggests κατεȋδε [had seen, though he did not speak]: and this, by a kind of zeugma, stands as verb to γγελος also.’ In support he cites only an atrocious zeugma from the MS. text of Hdt. iv. 106; but this has been corrected, as anyone may now see who will examine the text and apparatus of chs. (...) 106 and 107 as presented in Hude's edition. (shrink)

Sufficient conditions are given under which ratifiable acts exist.

Nazariyat, Journal for the History of Islamic Philosophy and Sciences, issued twice a year in English and Turkish (Nazariyat İslam Felsefe ve Bilim Tarihi Araştırmaları Dergisi), is a refereed international journal. It publishes original studies, critical editions of classical texts and book reviews on Islamic philosophy, kalām, theoretical aspects of Sufism and the history of sciences. The goal of Nazariyat is to contribute to the discovery, examination and reinterpretation of the theoretical traditions in the history of Islamic thought, by giving (...) special attention to the post-classical period of it. **ISSN: 2148-8088 E-ISBN: 2547-9415**. (shrink)