356 research outputs found
Dissecting the cellular and molecular mechanisms of Insulin-like growth factor binding protein-2 (IGFBP-2) action in a cancer cell model
No full text© 2013 Dr. Walid Jhan AzarPublications included in thesis:Azar, W. J., Azar, S. H. X., Higgins, S., Hu, J., Hoffman, A. R., Newgreen, D. F., Werther, G. A. & Russo, V. C. (2011). IGFBP-2 enhances VEGF gene promoter activity and consequent promotion of angiogenesis by neuroblastoma cells. Endocrinology, 152(9), 3332-3342. DOI: 10.1210/en.2011-1121Azar, W. J., Zivkovic, S., Werther, G. A. & Russo, V. C. (2013). IGFBP-2 nuclear translocation is mediated by a functional NLS sequence and is essential for its pro-tumorigenic actions in cancer cells. Oncogene. DOI: 10.1038/onc.2012.630Sabin, M. A., Russo, V. C., Azar, W., Yau, S. W., Kiess, W. & Werther, G. A. (2011). IGFBP-2 at the interface of growth and metabolism – implications for childhood obesity. Pediatric Endocrinology Reviews, 8(4), 382-393.IGFBP2 is one of the most highly expressed genes in the signature of human tumour cells. Elevated expression has been observed in almost every major malignancy. Importantly, IGFBP2 is frequently overexpressed in advanced cancers and is suggested to be involved in the metastatic process. IGFBP-2 is expressed both in the serum and in tumour tissues, where tumour aggressiveness is directly proportional to IGFBP-2 levels; hence, it is recognised as a valuable prognostic biomarker for many of these cancers. These clinical findings are also supported by in vitro studies showing that high levels of IGFBP-2 promote the tumorigenic potential of cancer cells.
IGFBP-2 is a secreted protein which binds both IGFs with high affinity. Traditionally, IGFBP-2 was known mainly to modulate IGFs actions by regulating their bioavailability in the peri-/extracellular space; hence, these were referred to as its IGF-dependent actions. However, it is now becoming increasingly clear that, apart from its IGF-dependent actions, IGFBP-2 also exerts IGF-independent effects in the absence of IGFs or in the absence of IGF receptor signalling. These effects are shown to be mediated via other functional domains of IGFBP-2, such as HBD and RGD, which are distinct from its IGF-binding domains. In addition, more recently there has been evidence of intracellular functions and growing speculation about potential nuclear actions of IGFBP-2. However, to date, there has been no definitive evidence to demonstrate the molecular mechanisms of IGF-independent, nor the intracellular/intranuclear actions, of IGFBP-2.
Therefore, the aim of these PhD studies was to dissect the cellular and molecular mechanisms of IGFBP-2 actions using a cancer cell model.
The first results chapter (Chapter 3) investigates the overexpression of IGFBP2 in a neuroblastoma cell line. This provides novel insights into the activation of a pro-tumorigenic gene expression profile in response to IGFBP-2 and sheds light onto its intranuclear actions, while also demonstrating the molecular mechanisms behind the regulation of a target gene, VEGF, by IGFBP-2. The second results chapter (Chapter 4) describes the precise nuclear import mechanisms of IGFBP-2, identifying, for the first time, a functional nuclear localisation signal sequence, and its interaction with a nuclear import receptor. The final results chapter (Chapter 5) describes the development and characterisation of a novel non-IGF-binding IGFBP-2 mutant.
In conclusion, these studies contribute to our steadily expanding knowledge regarding the role of IGFBP-2 in tumorigenesis, and provide novel insights into the underlying molecular and cellular mechanisms of IGFBP-2 in cancer. These studies also provide a great set of non-IGF-binding IGFBP-2 mutants, which with further characterisation and functional studies, will allow us to acquire more definitive evidence on the IGF-independent actions of IGFBP-2, and in turn, build on our current understanding of these actions. Finally, these studies also raise many exciting questions and uncover other avenues for IGFBP-2 research. Such studies are imperative for the understanding and development of IGFBP-2 as a novel therapeutic target
Knowledge Type Identification in API Documentation
No full text<p>This release contains the source code and instruction on how to obtain the dataset to reproduce the results presented in the following paper</p>
<pre><code>@inproceedings{FMM19,
title={On Using Machine Learning to Identify Knowledge in API Reference Documentation},
author={Fucci, Davide and M. Alizadeh B., Alireza and Maalej, Walid},
booktitle={27th ACM Joint European Software Engineering Conference and Symposium on the Foundations of Software Engineering},
pages={103--112},
year={2019},
doi={10.1145/3338906.3338943}
organization={IEEE}
}
</code></pre>
The formation of the classical tafsīr tradition : the Qurʼān commentary of al-Thaʻlabī (d. 427/1035) by Walid A. Saleh.
No full text"This work is both an introduction to the genre of classical tafsir and a detailed study of one of its major architects, al-Thalabi (d. 427/1035). The book offers a detailed study of the hermeneutical principles that governed al-Thalabi's approach to the Quran, principles which became the norm in later exegetical works. It is divided into three main sections: the first outlines the life and times of the author; the second is a detailed study of his major exegetical work, al-Kashf; the third charts a brief history of the genre of tafsir through documenting the reactions of later exegetes to al-Kashf. This work brings together material never examined before and tries to offer anew way of understanding the history of classical Quran exegesis."--Jacket.Includes bibliographical references (pages 251-259) and indexes."This work is both an introduction to the genre of classical tafsir and a detailed study of one of its major architects, al-Thalabi (d. 427/1035). The book offers a detailed study of the hermeneutical principles that governed al-Thalabi's approach to the Quran, principles which became the norm in later exegetical works. It is divided into three main sections: the first outlines the life and times of the author; the second is a detailed study of his major exegetical work, al-Kashf; the third charts a brief history of the genre of tafsir through documenting the reactions of later exegetes to al-Kashf. This work brings together material never examined before and tries to offer anew way of understanding the history of classical Quran exegesis."--Jacket
Exploring Author Context for Detecting Intended vs Perceived Sarcasm
No full textWe investigate the impact of using author context on textual sarcasm detection. We define author context as the embedded representation of their historical posts on Twitter and suggest neural models that extract these representations. We experiment with two tweet datasets, one labelled manually for sarcasm, and the other via tag-based distant supervision. We achieve state-of-the-art performance on the second dataset, but not on the one labelled manually, indicating a difference between intended sarcasm, captured by distant supervision, and perceived sarcasm, captured by manual labelling.<br/
Exploring Author Context for Detecting Intended vs Perceived Sarcasm
No full textWe investigate the impact of using author context on textual sarcasm detection. We define author context as the embedded representation of their historical posts on Twitter and suggest neural models that extract these representations. We experiment with two tweet datasets, one labelled manually for sarcasm, and the other via tag-based distant supervision. We achieve state-of-the-art performance on the second dataset, but not on the one labelled manually, indicating a difference between intended sarcasm, captured by distant supervision, and perceived sarcasm, captured by manual labelling.<br/
Peripubertal aromatase inhibition in male rats has adverse long-term effects on bone strength and growth and induces prostatic hyperplasia
No full text*This article is free to read on the publisher's website*\ud
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Aromatase inhibitors have been increasingly used in boys with growth retardation to prolong the duration of growth and increase final height. Multiple important roles of oestrogen in males point to potential adverse effects of this strategy. Although the deleterious effects of aromatase deficiency in early childhood and adulthood are well documented, there is limited information about the potential long-term adverse effects of peripubertal aromatase inhibition. To address this issue, we evaluated short-term and long-term effects of peripubertal aromatase inhibition in an animal model. Peripubertal male Wistar rats were treated with aromatase inhibitor letrozole or placebo and followed until adulthood. Letrozole treatment caused sustained reduction in bone strength and alteration in skeletal geometry, lowering of IGF1 levels, inhibition of growth resulting in significantly lower weight and length of treated animals and development of focal prostatic hyperplasia. Our observation of adverse long-term effects after peripubertal male rats were exposed to aromatase inhibitors highlights the need for further characterisation of long-term adverse effects of aromatase inhibitors in peripubertal boys before further widespread use is accepted. Furthermore, this suggests the need to develop more selective oestrogen inhibition strategies in order to inhibit oestrogen action on the growth plate, while beneficial effects in other tissues are preserved
Flaubert lecteur de l'Histoire naturelle de Pline
No full textThis article questions the relationship between flaubertian writing and the latin text that represents one of the major sources of Salammbo’s composition. It intends more specifically to examine the way in which the details taken from Pliny’s Natural History and which were diversely used by Flaubert during the composition of the “ roman carthaginois” were processed. In fact, various methods and techniques were implemented in the genesis : – combining data stemming from the author''s reading with issues of his own experience – condensating data – deliberately pursuing strangeness and seeking inaccuracy – description serving narration. With Flaubert, the ancient works lose their exemplary nature and become sources of documentation and the Ancients cease being the ideals they were during the renaissance and the classical periods. Analyzing these methods and processes can bring us to reflect on the poetic aspect of Flaubert’s writing largely based on documentation.Cet article s’interroge sur la relation qu’entretient l’écriture flaubertienne avec le texte latin et qui constitue l’un des ressorts clefs de la composition de Salammbô : il se propose plus précisément d’examiner la façon dont sont transformés les détails empruntés à l’Histoire naturelle de Pline, et qui sont diversement exploités par Flaubert pendant la composition du roman carthaginois. En effet, différentes méthodes et techniques sont utilisées au cours de la genèse de l’oeuvre : combinaison entre des données tirées des lectures de l’auteur et d’autres provenant de son expérience propre, condensation de données, recherche de l’étrangeté, imprécision volontaire, description au service de la narration. Avec Flaubert, les ouvrages anciens perdent leur exemplarité pour devenir sources de documentation et les Anciens cessent d’être des modèles comme ils l’étaient à la Renaissance et à l’époque classique. L’analyse de ces méthodes et procédés peut nous amener à réfléchir sur la poétique d''une écriture flaubertienne fondée en grande partie sur la documentation.Ezzine Walid. Flaubert lecteur de l'Histoire naturelle de Pline. In: Ktèma : civilisations de l'Orient, de la Grèce et de Rome antiques, N°35, 2010. pp. 393-401
Art and political dissent in postwar Lebanon: Walid Sadek's fi annani akbar min bikasu [bigger than picasso]
No full textTaking Walid Sadek's fi annani akbar min bikasu [bigger than picasso] as its starting point, this article examines relations of art and politics in post-civil war Lebanon. A tiny and inexpensive paperback related to Picasso unfolds into a work of art that raises questions about the place of art and political dissent. After situating bigger than picasso in the context of contemporary book art and artistic practices of the postwar generation in Lebanon, the article focuses on the juxtaposition of text and image. By placing narratives of art vandalism next to the image of a monument dedicated to the late Syrian President Hafiz al-Asad, bigger than picasso playfully and provocatively breaks with political taboos at a time when the silence about the Lebanese Civil War (1975-90) and about Lebanese-Syrian relations was met with increasing anxiety. At the same time, the work makes room for aesthetic inquiries, exploring new possibilities of art at the margins of cultural production. The article concludes that bigger than picasso brings to the fore the discrepancy between public monumentality and artistic practices, which in finding ways around political violence and censorship have recourse to ephemeral and private spheres, and holds unexpected meanings in ever-changing political circumstances. 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Book review: shadows of the holy land - Fred Halliday reviews more chapters in a long saga
No full textAuthor reviews: Nicholas Bethell, "The Palestine triangle"; Nathan Weinstock, "Zionism: false Messiah"; Jacob Landau, "Abdul-Hamid's Palestine"; I.F. Stone, "Underground to Palestine"; Walid Kazzila, "Palestine in the Arab dilemma"; Molly Izzard, "The Gulf
Second ever reported case of central cause of unilateral foot drop due to cervical disc herniation : Case report and review of literature
No full textBackground: Foot drop is defined as a weakness in the ankle and foot dorsiflexors. A disruption of the neural pathway starting from the motor prefrontal cortex and ending in the peroneal nerve can lead to foot drop. Foot drop due to lower motor neuron injury is well documented. However, foot drop due to a central cause of cervical disc prolapse is very rare. Case presentation: A 55-year-old male presenting with neck pain, right and left arms radicular pain and numbness, and unilateral right foot drop following cervical disc prolapse. The patient presented with upper motor neuron lesion signs. MRI showed cervical disc prolapse at two levels, confirming central cause of foot drop. The patient underwent anterior cervical decompression and fusion surgery. Discussion: Following decompression and fusion of involved cervical spine disc pathology, the patient had complete recovery of his right foot drop. Conclusions: Central causes, although rare, should be considered in the differential diagnosis of foot drop. Causes could be due to the compression effect of the cortico-spinal tract of the cervical spinal cord. Satisfactory results can be achieved upon correcting the causative lesion. CC BY 4.0© 2021 The Author(s)Guarantor Prof Dr. Walid El Ansari: [email protected]</p
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