Codelivery of Genistein and miRNA-29b to A549 Cells Using Aptamer-Hybrid Nanoparticle Bioconjugates.

This study aimed to evaluate the anti-cancer effect of a combination therapy of miRNA-29b and genistein loaded in mucin-1 (MUC 1)-aptamer functionalized hybrid nanoparticles in non-small cell lung cancer (NSCLC) A549 cell line. Genistein-miRNA-29b-loaded hybrid nanoparticles (GMLHN) was prepared and characterized. Particle size and zeta potential were measured using photon correlation spectroscopy (PCS). Encapsulation efficiency and loading efficiency were determined using HPLC. Preferential internalization of MUC 1-aptamer functionalized GMLHN by A549 cells was evaluated and compared to normal MRC-5 cells. The ability of GMLHN to downregulate targeted oncoproteins Phosphorylated protein kinase, strain AK, Thymoma (Phosphorylated protein kinase B) (pAKT), Phosphorylated phosphoinositide 3-kinase (p-PI3K), DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) and Myeloid Cell Leukemia Sequence 1 (MCL 1) was evaluated using western blot, while antiproliferative effect and ability to initiate apoptosis was also assessed in A549 cells. MUC 1-aptamer functionalized GMLHN nanoparticles were prepared. These nanoparticles were preferentially internalized by A549 cells but less so, in MRC-5 cells. pAKT, p-PI3K, DNMT3B and MCL 1 were efficiently downregulated by these nanoparticles without affecting the levels of AKT and PI3K in A549 cells. GMLHN demonstrated a superior antiproliferative effect compared to individual genistein and miRNA-29b-loaded nanoparticles. Results generated were able to demonstrate that genistein-miRNA-29b-loaded hybrid nanoparticles (GMLHN) could be a potential treatment modality for NSCLC because of the ability of the payloads to attack multiple targets

Multidimensional risk assessment for vehicle trajectories by using copulas

Fight against road unsafety is a French government priority. The policy conducted since 2002 allowed to obtain undeniable success. Despite this improvement, road accidents have very serious consequences on human level for road users. The proposed methods to reduce these accidents involve independence between criteria of accident risk. The objective of this study is to estimate the multidimensional risk of failure trajectory. It consists to investigate a new method of risk assessment in order to better characterize the dependence structure between the vehicle criteria for safety acceptance. This requires the use of simulation techniques such as copulas methods. This function connects the joint probability distribution to the marginal distribution. Thus, it contains all information on the dependence structure of models. However, the difficulty of multidimensional risk is to choose the copula which capture the better dependence between criteria. To select an adequate copula must be based on a statistical test. The khi2 test used in the framework of the adjustment of a parametric distribution to an empirical distribution is in this regard an interesting tool for the choice of copula. The experiments have shown the relevance and effectiveness of this method. The results will help to better assess the risk of failure trajectory for vehicles

Pathogen genetic diversity a challenge for vaccine development: Looking for the pathogen’s Achilles’ heel

Creation of variant forms has serious consequences in diagnostic, treatment strategies and the future vaccine development. Thus, the actual and future roles of the altered or emergent pathogens in the global pandemic of AIDS, Malaria, Flu and Ebola must be monitored in new molecular epidemiological studies. During the last 5 years, we studied the genetic structure of several pathogens such as 1] malaria parasite showing that gene deletion, recombination can occur and lead to false RDT negative and to the creation of new antigens (hybrid parasites); 2] in HIV, our findings indicate a shift in the virus population circulating over time in Mali. Those observations are suggesting that a vaccine development against those pathogens such Plasmodium falciparum parasite and HIV will be a challenge. Our approach that is to target pieces of antigens within a genome which must be well conserved across the specie and immunogenic enough in boosting the immune response. Four steps were identified in that approach which are: 1] Genome mining using computational and experimental tools to identify genes that encode proteins with promising vaccine antigens properties, 2] use of the Immunoinformatics tools to map protein sequences for short, linear putative T-cell epitopes CTL/ T helper, 3] then candidates are synthesized as peptides and evaluated for HLA binding and antigenicity (in vitro evaluation) and then 4] Prototype epitope-based vaccines are evaluated for immunogenicity in human Host (in vivo evaluation). Our laboratory has partnered with the GAIA foundation to test this approach in Mali

薄型容器内の水中放電誘起する衝撃波及び関連現象に関する研究

要約のみTohoku University孫明宇課

French Interference on Malian undergraduate students’ EFL writings: perspectives from teachers

Abstract: Writing in a foreign language can be challenging for non-native writers. According to the contrastive rhetoric theory, students’ first languages and cultures influence the linguistic and rhetorical choices of their written discourses in English (Kaplan, 1966). In Mali, West African country colonized by France, students’ indigenous languages are acquired in their family settings and are mainly used for oral purposes. Some of these languages have been elevated to the status of national languages with a codified alphabet but remain taught mainly at the primary level. French is therefore the language used to teach most subjects, including academic writing or composition. English is introduced as a foreign language in secondary school and students are just taught basic English in most subjects.  Students, therefore, learn academic writing or composition in French during their academic career before reaching university. This study set out to investigate difficulties undergraduate students face while writing their paragraphs in English. The purpose of this study is to examine possible interference of French on Malian undergraduate texts and explore the perspectives of teachers on this interference. Data were collected from both students and teachers through an in-depth set of interviews and writing analysis. The results revealed that students experience difficulties that are caused mainly by the interference from their education background, which is French.   Keywords: Composition, interference, French, English, undergraduate

Optimizing pentose sugar utilization in Escherichia coli for the production of biofuels

The hydrolysis of biomass yields a sugar mixture consisting mainly of glucose, arabinose and xylose. Effective metabolism of all sugars in biomass by a microorganism is regarded as essential for commercial biofuel production. However, two of the major challenges that we are currently faced with are the transport of sugars into the microorganism and the co-utilization of these sugars once they are in the cell. In order to engineer simultaneous multiple sugar utilization in Escherichia coli, a better understanding of the pentose sugar pathways is required. In this work, we have investigated the transport of sugars and the regulation of the sugar metabolic pathways within E. coli to engineer a strain most efficient in producing biofuels. While extensive research has been carried out to examine the transport mechanisms of sugars into the cell, this research shows that in addition to transporters that pump sugars into the cell, a number of proteins that pump sugars out of the cell are also expressed by E. coli. Using genetic approaches, we have demonstrated that by either deleting or overexpressing these efflux transporters we can respectively increase or decrease the uptake of pentose sugars, namely arabinose and xylose, which are abundantly present in the hemicellulose of biomass. In addition to examining transport mechanisms, this work has also focused on studying and controlling the metabolism of the pentose sugars. By using a novel targeted approach, we can utilize constitutive promoters and chromosomal integration to control the expression of certain metabolic genes, while relieving repression effects. This enables us to regulate the metabolism of pentose sugars such as xylose that are utilized by the cell less efficiently and allows for simultaneous metabolism of sugars, hence leading to a more efficient biofuel production process

Stakes of transnational civil society action : NGO advocacy interventions and the farmers of Mali’s cotton zone

This thesis examines how transnational advocacy networks operate across local, national, regional and international arenas. It takes a close look at the nature of peasant resistance and civil society in Mali, and explores how these interact with campaign and advocacy activities of Northern-based non-governmental organisations (NGOs). The central argument of this thesis is that these encounters have strengthened an elite, while marginalising alternative perspectives. This has happened through the collision of actors’ diverse interests, through competition between distinct framings of debate, and through differences in modes of political participation which reflect the power dynamics of the political arenas in which actors are rooted. The thesis is informed by the results of qualitative fieldwork research, which was carried out, mainly in Mali, between 2006 and 2008. By identifying the nature of connections and disconnections between actors at multiple levels, the thesis contributes to a more nuanced understanding of transnational civil society action

Human Gene Expression in Uncomplicated Plasmodium falciparum Malaria.

To examine human gene expression during uncomplicated P. falciparum malaria, we obtained three samples (acute illness, treatment, and recovery) from 10 subjects and utilized each subject's recovery sample as their baseline. At the time of acute illness (day 1), subjects had upregulation of innate immune response, cytokine, and inflammation-related genes (IL-1β, IL-6, TNF, and IFN-γ), which was more frequent with parasitemias >100,000 per μL and body temperatures ≥ 39°C. Apoptosis-related genes (Fas, BAX, and TP53) were upregulated acutely and for several days thereafter (days 1-3). In contrast, the expression of immune-modulatory (transcription factor 7, HLV-DOA, and CD6) and apoptosis inhibitory (c-myc, caspase 8, and Fas Ligand G) genes was downregulated initially and returned to normal with clinical recovery (days 7-10). These results indicate that the innate immune response, cytokine, and apoptosis pathways are upregulated acutely in uncomplicated malaria with concomitant downregulation of immune-modulatory and apoptosis inhibitory genes