Translationally controlled tumor protein (TCTP) has been implicated in a plethora of important cellular processes related to cell growth, cell cycle progression, malignant transformation and inhibition of apoptosis. Therefore, TCTP is now recognized as a potential therapeutic target in several cancers including prostate, breast and lung cancers. We previously showed that TCTP is overexpressed in castration-resistant prostate cancer (CRPC), and it has been implicated resistance to treatment. Recently, we developed TCTP antisense oligonucleotides (ASOs) to inhibit TCTP expression. However, the intracellular delivery and silencing activity of these oligonucleotides remains a challenge, and depend on the use of transfection agents and delivery systems. Here we show that lipid-modified ASO (LASOs) has improved penetration and efficiency in inhibiting TCTP expression in the absence of additional transfection agents, both in vitro and in vivo. Transfection with TCTP-LASO led to rapid and prolonged internalization via macropinocytosis, TCTP downregulation and significant decreased cell viability. We also show that lipid-modification led to delayed tumor progression in CRPC xenografts models, with no significant toxic effects observed.

We report on the use of phase-sensitive optical coherence tomography (PhS-OCT) to detect and track temporally and spatially shear wave propagation within tissue induced by ultrasound radiation force. Kilohertz-range shear waves are remotely generated in sample using focused ultrasound emission and their propagation is tracked using PhS-OCT. Cross-sectional maps of the local shear modulus are reconstructed from local estimates of shear wave speed in tissue-mimicking phantoms. We demonstrate the feasibility of combining ultrasound radiation force and PhS-OCT to perform high-resolution mapping of the shear modulus.

Linkage studies have revealed a linkage of mild malaria to chromosome 6p21 that contains the NCR3 gene encoding a natural killer cell receptor, whereas NCR3-412G>C (rs2736191) located in its promoter region was found to be associated with malaria in Burkina Faso. Here we confirmed the association of rs2736191 with mild malaria in a Congolese cohort and investigated its potential cis-regulatory effect. Luciferase assay results indicated that rs2736191-G allele had a significantly increased promoter activity compared to rs2736191-C allele. Furthermore, EMSAs demonstrated an altered binding of two nuclear protein complexes to the rs2736191-C allele in comparison to rs2736191-G allele. Finally, after in silico identification of transcription factor candidates, pull-down western blot experiments confirmed that both STAT4 and RUNX3 bind the region encompassing rs2736191 with a higher affinity for the G allele. To our knowledge, this is the first report that explored the functional role of rs2736191. These results support the hypothesis that genetic variation within natural killer cell receptors alters malaria resistance in humans.

Corneal scarring associated with various corneal conditions is a leading cause of blindness worldwide. The present study aimed to test the hypothesis that corneal stromal stem cells have a therapeutic effect and are able to restore the extracellular matrix organization and corneal transparency in vivo. We first developed a mouse model of corneal stromal scar induced by liquid nitrogen (N 2) application. We then reversed stromal scarring by injecting mouse or human corneal stromal stem cells in injured cornea. To characterize the mouse model developed in this study and the therapeutic effect of corneal stromal stem cells, we used a combination of in vivo (slit lamp, optical coherence tomography, in vivo confocal microscopy, optical coherence tomography shear wave elastography, and optokinetic tracking response) and ex vivo (full field optical coherence microscopy, flow cytometry, transmission electron microscopy, and histology) techniques. The mouse model obtained features early inflammation, keratocyte apoptosis, keratocyte transformation into myofibroblasts, collagen type III synthesis, impaired stromal ultrastructure, corneal stromal haze formation, increased corneal rigidity, and impaired visual acuity. Injection of stromal stem cells in N 2-injured cornea resulted in improved corneal transparency associated with corneal stromal stem cell migration and growth in the recipient stroma, absence of inflammatory response, recipient corneal epithelial cell growth, decreased collagen type III stromal content, restored stromal ultrastructure, decreased stromal haze, decreased corneal rigidity, and improved vision. Our study demonstrates the ability of corneal stromal stem cells to promote regeneration of transparent stromal tissue after corneal scarring induced by liquid nitrogen.

Several studies have provided evidence of both helpful and harmful effects of TNF on the outcome of Plasmodium falciparum malaria infection. Several TNF polymorphisms that are located within non-coding regions have been associated with parasitaemia, mild malaria or severe malaria. We investigated the association of TNF1304 (rs3093664), TNF-308 (rs1800629), TNF-238 (rs361525) and TNF-244 (rs673) with mild malaria and symptomatic maximum parasitaemia in a population-based design (n=310). We obtained nominal evidence for an association between symptomatic maximum parasitaemia and TNF-308, TNF-238, and TNF-244 on the one hand, and between the number of mild malaria attacks and TNF-244 on the other hand. After accounting for multiple tests, we confirmed the association of symptomatic maximum parasitaemia with TNF-244. We further provide bioinformatics and experimental evidence that TNF-244 has a cis-regulatory effect. This is the first report that emphasizes the potential role of TNF-244 in malaria.

The Pre-Tertiary fractured basement forms important hydrocarbon-bearing reservoirs in the Vietnam-Malaysia offshore area, and is being produced from such reservoirs in Vietnam where the authors have extensive working experiences for both clastics and fractured basement reservoirs and in both exploration and development phases. Due to their very small matrix porosity, the basement rocks become reservoirs only when they are strongly fractured. The quality of the fractured basement reservoirs depends on basement rock type, fracture density, and fracture characteristics including aperture, azimuth, dip, continuity, and fracture system intersection. Three-dimensional seismic data is applied widely to characterize these basement reservoirs. Based on results from applying many different seismic attributes to 3D seismic data from different Pre-Tertiary fractured basements in Vietnam and Malaysia, we demonstrate the utility of attributes in characterizing fractured basement reservoirs. Seismic attributes help predict the basement rock type and fracture characteristics from near top basement to deep inside basement. In the zone near the top of basement, the characteristics of fracture systems can be predicted by amplitude, coherence, curvature, and secondary derivative attributes. Deep inside the basement, relative acoustic impedance and its attributes have been successfully applied to predict the distribution of high fracture density, while dip and azimuth, ant-tracking, and gradient magnitude attributes have proven to be effective for predicting fracture characteristics. The accuracy of fracture characterization based on seismic attributes has been verified by drilling results.

This paper will describe the results of development drilling to date in the basement reservoir of the Ruby Field in the Mekong Basin, Offshore Vietnam. The results of joint research on the Ruby discovery wells and onshore basement exposures (Peter M. Tandom et al. 1997) were used to develop an interpretation model for the fractured and weathered granite reservoir. This model has proven very robust, and has now been further enhanced by applying more quantitative formation evaluation techniques to determine fracture aperture and porosity. Various acquisition techniques and computation algorithms have been tested to come up with an optimized logging program; giving consistent results compared with core analysis and production data. It is now possible to predict with some certainty the most prospective hydrocarbon bearing intervals, and work is currently being focused on the estimation of likely production rates. Failure to meet the expected well deliverables provides a criteria for identifying candidates for stimulation. These techniques will also be reviewed. As more wells are drilled, it has become possible to better correlate and map the producing horizons. This clearly allows better planning of the location of future wells, and the thickness of the reservoir section which needs to be penetrated, so optimizing field economics.

No abstract