Foreign policy and nation-state building in Algeria, 1962-1985

This study analyses the intimate relationship between foreign policy and nation-state building in Algeria since independence. It assumes that foreign policy stands as a part and parcel of the process of building a state and cementing national feelings in a society that emerged through a long period of colonisation and a violent struggle for liberation. This thesis is sub-divided into six chapters to highlight the link between foreign policy and the nation-state building process: Chapter One underlines the conceptions of the Algerian ideologists with regard to affirming the existence of an Algerian nation and a state well before French colonisation. It also attempts to locate the political forces that emerged as nation-builders and ascertain their achievements. In chapter Two, the decision-making process is scrutinized through the study of the main actors and institutions forming the foreign community and the interference in formulating and conducting the country's foreign policy. Sovereignty, as one of the basic foundations of a nation-state unit, constitutes the theme of the third Chapter and is analysed through the efforts of the Algerian leaders to assert their country's sovereignty vis-a-vis its former metropole, France. Chapter Four relates the state’s security and territorial integrity to the regional context, notably to Algeria's relations with her neighbours which have been marked by ideological differences and territorial disputes. Chapter Five deals with the efforts of Algeria to establish her identity on radical and technocratic perceptions of Arabo-Islamism at home and on a deep attachment to the policy of non-alignment abroad. Finally, Chapter Six focuses on the link between foreign policy and national economic development as it has been conceived by the state's technocracy and assesses the successes and failures of the economic policy as well as Algeria's role in North-South debates

First-in-class candidate therapeutics that target mitochondria and effectively prevent cancer cell metastasis : mitoriboscins and TPP compounds

Cancer stem cells (CSCs) have been proposed to be responsible for tumor recurrence, distant metastasis and drug-resistance, in the vast majority of cancer patients. Therefore, there is an urgent need to identify new drugs that can target and eradicate CSCs. To identify new molecular targets that are unique to CSCs, we previously compared MCF7 2D-monolayers with 3D-mammospheres, which are enriched in CSCs. We observed that 25 mitochondrial-related proteins were >100-fold over-expressed in 3D-mammospheres. Here, we used these 25 proteins to derive short gene signatures to predict distant metastasis (in N=1,395 patients) and tumor recurrence (in N=3,082 patients), by employing a large collection of transcriptional profiling data from ER(+) breast cancer patients. This analysis resulted in a 4-gene signature for predicting distant metastasis, with a hazard ratio of 1.91-fold (P=2.2e-08). This provides clinical evidence to support a role for CSC mitochondria in metastatic dissemination. Next, we employed a panel of mitochondrial inhibitors, previously shown to target mitochondria and selectively inhibit 3D-mammosphere formation in MCF7 cells and cell migration in MDA-MB-231 cells. Remarkably, these five mitochondrial inhibitors had only minor effects or no effect on MDA-MB-231 tumor formation, but preferentially and selectively inhibited tumor cell metastasis, without causing significant toxicity. Mechanistically, all five mitochondrial inhibitors have been previously shown to induce ATP-depletion in cancer cells. Since 3 of these 5 inhibitors were designed to target the large mitochondrial ribosome, we next interrogated whether genes encoding the large mitochondrial ribosomal proteins (MRPL) also show prognostic value in the prediction of distant metastasis in both ER(+) and ER(-) breast cancer patients. Interestingly, gene signatures composed of 6 to 9 MRPL mRNA-transcripts were indeed sufficient to predict distant metastasis, tumor recurrence and Tamoxifen resistance. These gene signatures could be useful as companion diagnostics to assess which patients may benefit most from anti-mito-ribosome therapy. Overall, our studies provide the necessary proof-of-concept, and functional evidence, that mitochondrial inhibitors can successfully and selectively target the biological process of cancer cell metastasis. Ultimately, we envision that mitochondrial inhibitors could be employed to develop new treatment protocols, for clinically providing metastasis prophylaxis, to help prevent poor clinical outcomes in cancer patients

Identification of Two-shaft Gas Turbine Variables Using a Decoupled Multi-model Approach With Genetic Algorithm

In industrial practice, the representation of the dynamics of nonlinear systems by models linking their different operating variables requires an identification procedure to characterize their behavior from experimental data. This article proposes the identification of the variables of a two-shafts gas turbine based on a decoupled multi-model approach with genetic algorithm. Hence the multi-model is determined in the form of a weighted combination of the decoupled linear local state space sub-models, with optimization of an objective cost function in different modes of operation of this machine. This makes it possible to have robust and reliable models using input / output data collected on the examined system, limiting the influence of errors and identification noises

Le gène hairless de la souris : Fonctions à la racine du poil et au coeur d’une subtile pléiotropie

Le gène hairless (hr) des mammifères code pour une protéine nucléaire impliquée dans le contrôle du renouvellement du follicule pileux. Cette protéine est un cofacteur de récepteurs nucléaires d’hormones qui régulent la transcription de gènes cibles au cours de la différentiation de l’épiderme et du cycle du poil. La protéine Hairless (HR) fait partie de grands complexes multiprotéiques capables de réprimer la transcription, en association avec des facteurs de remodelage de la chromatine comme les histones désacétylases. Chez les mammifères, le locus hairless est la cible de nombreuses mutations alléliques dont les effets sont pléiotropiques. Ces altérations entraînent l’apparition d’un phénotype cutané complexe, caractérisé par la perte progressive et irréversible d’un pelage d’apparence normale au cours des premières semaines de vie post-natale. L’analyse de la littérature sur le gène hairless chez la souris et chez l’homme permet d’attribuer des différences morphologiques spécifiques à chaque mutant, aussi bien au niveau de l’épiderme et du follicule pileux que dans d’autres tissus où le gène est exprimé au cours du développement. Ces résultats suggèrent que l’intégrité du gène hairless est requise pour le déroulement correct de la morphogenèse d’organes aussi différents que l’épiderme, l’oreille interne, l’ovaire ou le thymus. Le gène hairless semble ainsi faire partie de circuits et de cascades d’interactions géniques dont le contrôle moléculaire est fondamentalement inconnu. La variété des phénotypes alléliques souligne l’importance de l’analyse moléculaire du locus hairless pour identifier les altérations géniques impliquées dans les différentes mutations détectées. Les recherches concernant la mutation hairless ont été particulièrement dynamiques pendant les dernières années, depuis que l’homologue de ce gène a pu être mis en évidence chez l’homme. Cependant, un bon nombre de questions reste en suspens, notamment quant au site exact d’activité du gène hairless au sein des nombreuses populations cellulaires du follicule pileux, son rôle précis au cours de la morphogenèse, sa localisation au sein des voies de signalisation, ainsi que l’identité des partenaires et des cibles de la protéine Hairless.The hairless gene in mammals encodes a nuclear factor that is highly expressed in skin and appears to control hair follicle integrity and cycling. In the absence of a normal and functional Hairless (Hr) protein, the hair bulb undergoes premature apoptosis during the first catagen stage of the hair cycle. The most striking effects of the mutation are loss of hair follicles and formation of epidermal utricles and dermal cysts. The hairless gene expression appears to be widespread and temporally regulated. The gene is strongly expressed in different compartments of the brain. Hairless mRNAs were detected in cartilage, gonads, thymus and colon. In addition to alopecia, hairless mice strains show subtle defects in the development and differentiation of various tissues and organs. The Hr protein is localised in cell nuclei and functions as a transcriptional regulator. Although its role has not been resolved in molecular terms, it was demonstrated that Hr is able to interact with multiple nuclear hormone receptors. Hr seems to be a part of a large multiprotein complex capable to repress transcription by its association to chromatin remodelling factors such as histone deacetylases. Recent experimental data suggest that Hr might be involved in Hox gene regulation, cell adhesion modulation and progenitor cells identity. At least in the skin, but probably in other organs, the Hr repressor seems to be responsible for the timing of epithelial cells differentiation

Evaluation of Reliability Indices for Gas Turbines Based on the Johnson SB Distribution: Towards Practical Development

Recent advancements in computer engineering have provided effective solutions for processing and analyzing complex systems and big data. Consequently, the adjustment and standardization of this data play a crucial role in addressing issues related to the monitoring of industrial systems. In this study, we propose a reliability approach for gas turbines to identify and characterize their degradation using operational data. We introduce a method for adjusting turbine reliability data, which resolves the challenges associated with the nature of these operating data. This enables us to determine a mathematical function that models the relationships between turbine reliability parameters and evaluate the impact of reliability practices in terms of availability. Additionally, we determine the survival function and employ it as a lifespan distribution model by estimating the parameters of the Johnson SB function. Furthermore, we calculate the failure rates and mean time between good operations for this rotating machine under different operating conditions. The obtained results allow us to estimate the parameters of the distribution that best fit the turbine reliability data, which are validated through statistical and graphical tests. We assess the goodness-of-fit using mean square error and reliability tests such as Kolmogorov-Smirnov

IN VITRO EVALUATION OF BIOLOGICAL ACTIVITIES OF PISTACIA LENTISCUS AQUEOUS EXTRACT

Objective: The aim of this study was to study the antioxidant potential and the antibacterial activity of leaves aqueous extract of Pistacia Lentiscus as well as the protective effect of this extract against the haemolysis in hypotonic condition, in oxidative stress and in the existence of saponin injury.Methods: We studied the antioxidant capacity through the DPPH assay, H2O2 scavenging activity, Ferric-reducing power (FRAP) assay, total antioxidant assay and the antibacterial activity using the disc diffusion method. We also investigated the haemolytic activity with the spectrophotometric method.Results: The result showed that the aqueous extract had a good antioxidant capacity, which was calculated as IC50. IC50 of the aqueous extract was found to be 9.89±0.7µg/ml for DPPH scavenging, 200±18.02µg/ml for H2O2 scavenging assay, 54.06±12.66µg/ml for Ferric-reducing power (FRAP) and 500±22.3 µg/ml for total antioxidant capacity. The aqueous extract also inhibited the growth of the tested bacterial strains with a maximum inhibition zone of 30.33±5.5 mm observed on Pseudomonas aeruginosa for wood-seed and a moderate activity against all other strain. The haemolytic analysis showed that the aqueous extract is not toxic for the human erythrocytes and protects them against the oxidative and osmotic stress and also against saponin injury.Conclusion: The results of our study suggest that the aqueous extract of leaves of Pistacia lentiscus possess potent anti-haemolytic activity, are a good source of natural antioxidant.Â

Salvia fruticosa Induces Vasorelaxation in Rat Isolated Thoracic Aorta: Role of the PI3K/Akt/eNOS/NO/cGMP Signaling Pathway

Salvia fruticosa (SF) Mill. is traditionally used for its antihypertensive actions. However, little is known about its pharmacologic and molecular mechanisms of action. Here we determined the effects of an ethanolic extract of SF leaves on rings of isolated thoracic aorta from Sprague-Dawley rats. Our results show that SF extract increased nitric oxide production and relaxed endothelium-intact rings in a dose-dependent (0.3 µg/ml–1 mg/ml) manner, and the maximum arterial relaxation (Rmax) was significantly reduced with endothelium denudation. Pretreatment of endothelium-intact rings with L-NAME (a non-selective inhibitor of nitric oxide synthase, 100 µM), or ODQ (an inhibitor of soluble guanylyl cyclase, 10 µM) significantly diminished SF-mediated vasorelaxation. Furthermore, SF induced Akt phosphorylation as well as increased cGMP levels in rings treated with increasing doses of SF. Prior exposure to PI3K inhibitors, wortmannin (0.1 µM) or LY294002 (10 µM), decreased cGMP accumulation and attenuated the SF-induced vasorelaxation by approximately 50% (Rmax). SF-evoked relaxation was not affected by indomethacin, verapamil, glibenclamide, tetraethylammonium, pyrilamine or atropine. Taken together, our results indicate that SF induces endothelium-dependent vasorelaxation through the PI3K/Akt/eNOS/NO/sGC/cGMP signaling pathway. Our data illustrate the health-orientated benefits of consuming SF which may act as an antihypertensive agent to reduce the burden of cardiovascular complications.Scopu

Marjoram Relaxes Rat Thoracic Aorta Via a PI3-K/eNOS/cGMP Pathway.

Despite pharmacotherapeutic advances, cardiovascular disease (CVD) remains the primary cause of global mortality. Alternative approaches, such as herbal medicine, continue to be sought to reduce this burden. is recognized for many medicinal values, yet its vasculoprotective effects remain poorly investigated. Here, we subjected rat thoracic aortae to increasing doses of an ethanolic extract of (OME). OME induced relaxation in a dose-dependent manner in endothelium-intact rings. This relaxation was significantly blunted in denuded rings. N(ω)-nitro-l-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) significantly reduced the OME-induced vasorelaxation. Cyclic guanosine monophosphate (cGMP) levels were also increased by OME. Moreover, wortmannin or LY294002 significantly reduced OME-induced vasorelaxation. Blockers of ATP-sensitive or Ca2+-activated potassium channels such as glibenclamide or tetraethylamonium (TEA), respectively, did not significantly affect OME-induced relaxation. Similarly, verapamil, a Ca channel blocker, indomethacin, a non-selective cyclooxygenase inhibitor, and pyrilamine, a H1 histamine receptor blocker, did not significantly modulate the observed relaxation. Taken together, our results show that OME induces vasorelaxation via an endothelium-dependent mechanism involving the phosphoinositide 3-kinase (PI3-K)/ endothelial nitric oxide (NO) synthase (eNOS)/cGMP pathway. Our findings further support the medicinal value of marjoram and provide a basis for its beneficial intake. Although consuming marjoram may have an antihypertensive effect, further studies are needed to better determine its effects in different vascular beds