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First Use of Bedaquiline in Democratic Republic of Congo: Two Case Series of Pre Extensively Drug Resistant Tuberculosis  [PDF]
Murhula Innocent Kashongwe, Leopoldine Mbulula, Brian Bakoko, Pamphile Lubamba, Murielle Aloni, Simon Kutoluka, Pierre Umba, Luc Lukaso, Michel Kaswa, Jean Marie Ntumba Kayembe, Zacharie Munogolo Kashongwe
Journal of Tuberculosis Research (JTR) , 2018, DOI: 10.4236/jtr.2018.62012
Abstract: In this manuscript the authors have studied the first two patients who were successfully treated with the treatment regimen containing Bedaquiline as second-line drug. The patients were diagnosed with pre-extensively drug-resistant tuberculosis (preXDR TB) whose prognosis was fatal in Democratic Republic of Congo (DRC). Bedaquiline is arguably one of the molecules of the future in the management of ultra-resistant tuberculosis. However, a larger cohort study may help to establish its effectiveness. Case report: Patients 1, 29 years old, with a history of multidrug-resistant TB (MDR-TB) one year previously. He showed signs of TB impregnation again 6 months after the last treatment. Bascilloscopy was positive again. The pre-extensively tuberculosis (pre-XDR TB) diagnosis was made by the Hain test (GenoType® MTBDRsl, Hain Lifescience). Patient 2, brother of the first patient, with a history of MDR TB a year before. He had low back pain with right parietal dorso swelling four months after the last treatment. The x-ray of the column showed L4-L5 disc disease. Parietal ultrasound showed a parietal abscess to the right of thoracic vertebrae with fistulization. Surgical biopsy and pus culture confirmed the diagnosis of Pre-XDR Extrapulmonary TB. The treatment regimen was the same for both patients: 6 months with Amikacin (Am) Bedaquiline (Bdq) Prothionamide (Pto) Paraamino Salicylic acid (PAS) Linezolid (Lzd) Cycloserine (Cs) Pyrazinamide (Z) and 14 months with PAS Lzd Cs Z. The side effects were minor. Bacteriological controls (smears and cultures) after 20 months of treatment are negative to date.
Conservation anchors in the vertebrate genome
Ronny Aloni, Doron Lancet
Genome Biology , 2005, DOI: 10.1186/gb-2005-6-7-115
Abstract: One of the most exciting recent outcomes of comparative genomics is the realization that when two or more vertebrate genomes are compared via phylogenetic footprinting, numerous highly similar non-coding segments emerge [1-4]. Many acronyms have been proposed for such highly conserved segments (Table 1); here they are referred to as ANCORs (ancestral non-coding conserved regions). Several recent papers address this topic in new ways, and refer to the origin and potential function of such conserved sequences.Initially, small-scale analyses comparing human and mouse (or other species) suggested conservation outside coding regions [5,6]. The identification of such conservation in the vicinity of specific genes (in proximal flanking regions, untranslated regions or UTRs, and introns) helped in the exploration of corresponding regulatory regions. Somewhat broader studies suggested sequence conservation in large sets of orthologous pairs [3,7,8]. The advent of full genomic sequences of human [9] and mouse [10] allowed the first large-scale analyses not limited to gene-related regions. A comparison between human chromosome 21 and the syntenic region in mouse [11] revealed a significant number of noncoding conserved elements, many of them far from gene-coding regions [12].Different reports use not only different nomenclature, but also different definitions in terms of compared species, ANCOR length, and percentage identity. We propose to unite these parameters by using a labeling system that refers to frequency within the genome (Figure 1), a property that follows from any filtering process. Thus, for example, segments defined as being within the top 5% of interspecies conservation [13] will be denoted here as ANCOR5%, while much more highly conserved 250 base-pair (bp) segments, which have a count of only 256 within 3 × 109 bp of human-rodent sequence [14], have an incidence of 0.002% and are therefore labeled ANCOR0.002% (see Additional data file 1). Thus, different repor
Comparative Evaluation of Tractor Trolley Axle by Using Finite Element Analysis Approach
Sanjay Aloni,Sandip Khedkar
International Journal of Engineering Science and Technology , 2012,
Abstract: Tractor trolley or trailers are very popular and cheaper mode of goods transport in rural as well as urban area. But these trailers are manufactured in small scale to moderate scale industry. Especially in the small- and middle-scale agricultural machinery industry, insufficient use of new technology and new design features can cause problems such as breakdowns and failures during field operations. In Present work finite element analysis approach is used to modify existing rear axle of tractor trolley. Fatigue failure of the rear axle finite element model was predicted after the dynamic load was imposed on it. For analysis, a 6.0 ton 2 wheeler tractor trolley i.e. semitrailer manufactured by Awachat Industries Ltd., Wardha is selected. The finite element analysis of existing rear axle of tractor trolley revealed the stresses distribution on rear axle. So, an effort is made to modify the design of existing rear axle along with change of material so that advantage of weight reduction along with safe stress can be obtained.
Quand l’écriture c’est un tableau : La maison imaginaire chiriquienne
Murielle Martin
Voix Plurielles , 2010,
Abstract: Dans cet article, il est question du peintre Giorgio de Chirico qui ne travaille pas seulement une surface à peindre mais construit des lieux imaginaires où tout évolue selon le parcours de recherche du texte narratif d'Hebdomeros. Il semble alors intéressant de croiser l'approche de la réalisation picturale de La Tour Rouge (1913) comme résultat littéraire et pictural de la Maison imaginaire de l'artiste.
Reflections on a Marine Venus (1953) : le détour par Rhodes dans la trilogie des les de Lawrence Durrell
E-rea : Revue électronique d’études sur le Monde Anglophone , 2005, DOI: 10.4000/erea.535
Abstract: Il s’agit ici de s’interroger sur la place qu’occupe le deuxième récit de voyage dans la trilogie durrellienne composée de Prospero’s Cell, publié en 1945 et consacré à l’ le de Corfou, où Durrell a séjourné de 1935 à 1941, de Reflections on a Marine Venus, publié en 1953 et consacré à l’ le de Rhodes suite à un séjour effectué de 1945 à 1947 et de Bitter Lemons, publié en 1957 après le séjour de Durrell à Chypre de 1953 à 1956. Cette étude vise ainsi à apporter un complément à la récente con...
Les ressorts de l’essor de la société civile en Guadeloupe Springs of expansion of civil society in Guadeloupe
Murielle Vairac
études Caribeénnes , 2012, DOI: 10.4000/etudescaribeennes.4898
Abstract: Les effets de la crise du capitalisme se sont traduits en Guadeloupe en janvier 2009 par un mouvement social sans précédent, dirigé par un collectif qui a suscité l’adhésion en raison de son expression du malaise social et de la gestion des revendications adressées au gouvernement. Ce mouvement social est innovant en Guadeloupe en raison de la pluralité des acteurs et de la nature de ses revendications. C’est donc sur son sens qu’il convient de s’interroger. Une société civile s’est réveillée créant de nouveaux espaces de débat. Capitalism’s crisis effects resulted in social movement unprecedented led by a group that mobilized in the style of expressing unrest and managing demands that were sent to French government. This social movement is new in Guadeloupe because of variety actions and type of demands. It’s therefore necessary to consider its meaning: a civil society woke up creating new spaces for debate.
Ancient genomic architecture for mammalian olfactory receptor clusters
Ronny Aloni, Tsviya Olender, Doron Lancet
Genome Biology , 2006, DOI: 10.1186/gb-2006-7-10-r88
Abstract: We developed a new and general tool for genome-wide definition of genomic gene clusters conserved in multiple species. Syntenic orthologs, defined as gene pairs showing conservation of both genomic location and coding sequence, were subjected to a graph theory algorithm for discovering CLICs (clusters in conservation). When applied to ORs in five mammals, including the marsupial opossum, more than 90% of the OR genes were found within a framework of 48 multi-species CLICs, invoking a general conservation of gene order and composition. A detailed analysis of individual CLICs revealed multiple differences among species, interpretable through species-specific genomic rearrangements and reflecting complex mammalian evolutionary dynamics. One significant instance involves CLIC #1, which lacks a human member, implying the human-specific deletion of an OR cluster, whose mouse counterpart has been tentatively associated with isovaleric acid odorant detection.The identified multi-species CLICs demonstrate that most of the mammalian OR clusters have a common ancestry, preceding the split between marsupials and placental mammals. However, only two of these CLICs were capable of incorporating chicken OR genes, parsimoniously implying that all other CLICs emerged subsequent to the avian-mammalian divergence.Olfactory receptor (OR) genes constitute the largest superfamily in the vertebrate genome, with several hundred genes per species [1-3]. This large repertoire of receptors mediates the sense of smell through the recognition of diverse volatile molecules, used to detect food, predators, and mates. Mammalian OR genes reside in about 50 genomic clusters of one to several dozen genes, which are dispersed among many chromosomes [4,5]. Although the number of clusters is similar among species, the typical cluster size varies significantly because of extensive lineage-specific evolutionary events (for example, inter- and intra-chromosomal gene duplications and genomic deletions) [3,6
A probabilistic classifier for olfactory receptor pseudogenes
Idan Menashe, Ronny Aloni, Doron Lancet
BMC Bioinformatics , 2006, DOI: 10.1186/1471-2105-7-393
Abstract: To characterize inactive ORs with intact open reading frame, we have developed a probabilistic Classifier for Olfactory Receptor Pseudogenes (CORP). This algorithm is based on deviations from a functionally crucial consensus, constituting sixty highly conserved positions identified by a comparison of two evolutionarily-constrained OR repertoires (mouse and dog) with a small pseudogene fraction. We used a logistic regression analysis to assign appropriate coefficients to the conserved position and thus achieving maximal separation between active and inactive ORs. Consequently, the algorithms identified only 5% of the mouse functional ORs as pseudogenes, setting an upper limit of 0.05 to the false positive detection. Finally we used this algorithm to classify the 384 purportedly intact human OR genes. Of these, 135 were predicted as likely encoding non-functional proteins, and 38 were segregating between active and inactive forms due to missense polymorphisms.We demonstrated that the CORP algorithm is capable to distinguish between functional and non-functional OR genes with high precision even when the encoded protein would differ by a single amino acid. Using the CORP algorithm, we predict that ~70% of human OR genes are likely non-functional pseudogenes, a much higher number than hitherto suspected. The method we present may be employed for better annotation of inactive members in other gene families as well.CORP algorithm is available at: http://bioportal.weizmann.ac.il/HORDE/CORP/ webcitePseudogenes, non-functional gene relics, are highly abundant genome-wide, with an estimated count of at least ~20,000 in the human genome [1,2]. A majority of these (~70%), are processed pseudogenes generated by reverse transcription of mRNAs followed by random genomic integration and thus, resulting in promoter region loss. The remainder non-processed pseudogenes are the result of gene duplication followed by mutational inactivation of one of the redundant copies. Pseudogenes ar
Usefulness of Mendelian Randomization in Observational Epidemiology
Murielle Bochud,Valentin Rousson
International Journal of Environmental Research and Public Health , 2010, DOI: 10.3390/ijerph7030711
Abstract: Mendelian randomization refers to the random allocation of alleles at the time of gamete formation. In observational epidemiology, this refers to the use of genetic variants to estimate a causal effect between a modifiable risk factor and an outcome of interest. In this review, we recall the principles of a “Mendelian randomization” approach in observational epidemiology, which is based on the technique of instrumental variables; we provide simulations and an example based on real data to demonstrate its implications; we present the results of a systematic search on original articles having used this approach; and we discuss some limitations of this approach in view of what has been found so far.
Zwanzig-Mori projection operators and EEG dynamics: deriving a simple equation of motion
David Hsu, Murielle Hsu
BMC Biophysics , 2009, DOI: 10.1186/1757-5036-2-6
Abstract: PACS code: 87.19.ljThe electrical activity of the brain has intrigued scientists since the invention of the electroencephalogram (EEG) [1,2]. Scalp and intracranial EEG's are now in widespread clinical use in the diagnosis and management of epilepsy and other neurological disorders. These applications rely on empirical correlations between certain EEG patterns with specific neurological disorders. Intense interest exists in trying to understand EEG dynamics at a deeper level, so as to extract ever more information about brain health and function. These efforts fall into two classes: those which are largely empirical, based on traditional correlations between EEG patterns and clinical observations, and those which are theory-based, where one has in mind a certain model of brain dynamics and then one tries to interpret EEG patterns in terms of the theoretical model. In the empirical class are recent efforts to correlate high frequency oscillations with epileptogenic tissue [3]. In the theory-based class, the most celebrated approach is the cable theory of Hodgkin and Huxley [4]. This theory can be scaled up using compartmental models to describe networks of thousands or even millions of neurons using high power computers. In the hands of a master, much insight can come from such simulations [5]. However, these methods are computationally intensive. They are not easily scaled to truly macroscopic levels and they are not amenable to the clinical diagnostic situation where one wants to know, for specific EEG samples from specific individuals, whether a certain brain pathology is present.Mesoscopic and macroscopic level theories of EEG dynamics have also been proposed, each based on a plausible basic postulate or mathematical model of the electrical activity of the brain [2,6-8]. The methods of nonlinear dynamics (chaos theory) also fall into this class and have been applied to seizure prediction [9,10].It would be desirable to base a macroscopic theory of EEG dynamics on
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