Nitroreductase-Mediated Release of Inhibitors of Lysine-Specific Demethylase 1 (LSD1) from Prodrugs in Transfected Acute Myeloid Leukaemia Cells

Lysine-specific demethylase 1 (LSD1) has evolved as a promising therapeutic target for cancer treatment, especially in acute myeloid leukaemia (AML). To approach the challenge of site-specific LSD1 inhibition, we developed an enzyme-prodrug system with the bacterial nitroreductase NfsB (NTR) that was expressed in the virally transfected AML cell line THP1-NTR⁺. The cellular activity of the NTR was proven with a new luminescent NTR probe. We synthesised a diverse set of nitroaromatic prodrugs that by design do not affect LSD1 and are reduced by the NTR to release an active LSD1 inhibitor. The emerging side products were differentially analysed using negative controls, thereby revealing cytotoxic effects. The 2-nitroimidazolyl prodrug of a potent LSD1 inhibitor emerged as one of the best prodrug candidates with a pronounced selectivity window between wild-type and transfected THP1 cells. Our prodrugs are selectively activated and release the LSD1 inhibitor locally, proving their suitability for future targeting approaches.     

Finite difference transmission line model for the design of safe multi-section cables in MRI

Magnetic Resonance Materials in Physics, Biology and Medicine - To show the relevance of a simple finite difference transmission line model to help design safe implanted cables in 1.5T MRI’s...     

Inverse wave field extrapolation: a different NDI approach to imaging defects

Nondestructive inspection (NDI) based on ultrasound is widely used. A relatively recent development for industrial applications is the use of ultrasonic array technology. Here, ultrasonic beams generated by array transducers are controlled by a computer. This makes the use of arrays more flexible than conventional single-element transducers. However, the inspection techniques have principally remained unchanged. As a consequence, the properties of these techniques, as far as characterization and sizing are concerned, have not improved. For further improvement, in this paper we apply imaging theory developed for seismic exploration of oil and gas fields on the NDI application. Synthetic data obtained from finite difference simulations is used to illustrate the principle of imaging. Measured data is obtained with a 64-element linear array (4 MHz) on a 20-mm thick steel block with a bore hole to illustrate the imaging approach. Furthermore, three examples of real data are presented, representing a lack of fusion defect, a surface breaking crack, and porosity.     

Effects of voluntary contraction on tibial nerve somatosensory evoked potentials: gating of specific cortical responses

We evaluated vertex-parietal P37, N50, and contralateral N37 somatosensory evoked potentials (SEPs) to posterior tibial nerve stimulation during weak (20 to 30%) and strong (80 to 90%) ipsilateral gastrocnemius-soleus contraction. The results were compared with data obtained during full relaxation. P37 and N50 were attenuated significantly during weak contraction and then abolished during strong contraction, whereas the contralateral N37 was not. The N37 potential spreads over the vertex and over the ipsilateral parietal region during strong contraction. The Cz'-F3 montage was not appropriate for detecting these SEP patterns. These findings suggest that thalamic or cortical gating mechanisms affect specific cortical responses. P37 and N50 could reflect the arrival of the afferent volley into the motor areas from thalamic and cortical (subareas 1 and 2 of S1) projections. N37 could be generated in subarea 3b. Differential analysis of N37 and P37 is required in clinical practice, mainly in those conditions that involve the motor system and in those conditions in which tonic muscular activity is increased.     

Psychological characteristics of South African street children

Research has shown that no treatment program designed for street children can succeed unless the community is prepared to respect, protect, and provide opportunities for them (Tacon, cited in Schurink & Rip, 1993). Unfortunately, these children are abused in many parts of the world (Aptekar, 1994). This paper investigates why the general public, as well as those charged with enforcing the law, often treat street children with scorn and hostility.     

Minimally invasive coronary bypass: experience at the Erasme Hospital in 1997-1998

Since the launching of cardiopulmonary bypass in 1952 the landscape of cardiac surgery has been marked by a major milestone every ten years. Though most of the cardiopathies can be surgically treated with satisfactory results in up to 90% of the cases, we must try to improve the existing results. That means--Can we do better, cheaper and less invasive? Several new surgical approaches aiming at so doing are discussed in the present report: Minimally invasive direct coronary arterial bypass (MIDCAB) which is performed through a small anterior thoracotomy; Beating heart revascularization through sternotomy; Heart Port approach; Trans Myocardial Laser Revascularization (TMLR). Those new technologies respectively offer specific advantages to the existing therapies thus represent promising alternatives in selected subcategories of patients.     

Analysis of the laser-cladding process for stellite on steel

Laser-cladding experiments have been performed with STELLITE 6 powder on mild steel substrates, using a 1.5 kW linearly polarized continuous wave CO₂ laser as a heat source. The clad height, the mass efficiency, the dimensions of the melt pool, as well as the global absorptivity, were measured as functions of the powder feed rate and the scanning speed. A quantitative analytical model of the process is proposed, based on the overall mass and energy balance. It allows the calculation of the mass efficiency and of the global absorptivity, taking into account the incorporation of the powder into the melt pool as well as the energy absorbed by the powder jet and the substrate. It successfully explains the experimental results and demonstrates the role played by the melt pool inclination with respect to the substrate. A processing diagram is given to find rapidly the optimal laser treatment conditions and the desired clad height. It is discussed with respect to the other limiting conditions of the process, the geometrical maximum powder efficiency, the porosity, the dilution, and the maximum power of the laser installation.     

The Use of Pro-Angiogenic and/or Pro-Hypoxic miRNAs as Tools to Monitor Patients with Diffuse Gliomas

IDH (isocitrate dehydrogenase) mutation, hypoxia, and neo-angiogenesis, three hallmarks of diffuse gliomas, modulate the expression of small non-coding RNAs (miRNA). In this paper, we tested whether pro-angiogenic and/or pro-hypoxic miRNAs could be used to monitor patients with glioma. The miRNAs were extracted from tumoral surgical specimens embedded in the paraffin of 97 patients with diffuse gliomas and, for 7 patients, from a blood sample too. The expression of 10 pro-angiogenic and/or pro-hypoxic miRNAs was assayed by qRT-PCR and normalized to the miRNA expression of non-tumoral brain tissues. We confirmed in vitro that IDH in hypoxia (1% O₂, 24 h) alters pro-angiogenic and/or pro-hypoxic miRNA expression in HBT-14 (U-87 MG) cells. Then, we reported that the expression of these miRNAs is (i) strongly affected in patients with glioma compared to that in a non-tumoral brain; (ii) correlated with the histology/grade of glioma according to the 2016 WHO classification; and (iii) predicts the overall and/or progression-free survival of patients with glioma in univariate but not in a multivariate analysis after adjusting for sex, age at diagnosis, and WHO classification. Finally, the expression of miRNAs was found to be the same between the plasma and glial tumor of the same patient. This study highlights a panel of seven pro-angiogenic and/or pro-hypoxic miRNAs as a potential tool for monitoring patients with glioma.     

Growth and characterization of gold catalyzed SiGe nanowires and alternative metal-catalyzed Si nanowires

The growth of semiconductor (SC) nanowires (NW) by CVD using Au-catalyzed VLS process has been widely studied over the past few years. Among others SC, it is possible to grow pure Si or SiGe NW thanks to these techniques. Nevertheless, Au could deteriorate the electric properties of SC and the use of other metal catalysts will be mandatory if NW are to be designed for innovating electronic. First, this article's focus will be on SiGe NW's growth using Au catalyst. The authors managed to grow SiGe NW between 350 and 400°C. Ge concentration (x) in Si1-xGex NW has been successfully varied by modifying the gas flow ratio: R = GeH4/(SiH4 + GeH4). Characterization (by Raman spectroscopy and XRD) revealed concentrations varying from 0.2 to 0.46 on NW grown at 375°C, with R varying from 0.05 to 0.15. Second, the results of Si NW growths by CVD using alternatives catalysts such as platinum-, palladium- and nickel-silicides are presented. This study, carried out on a LPCVD furnace, aimed at defining Si NW growth conditions when using such catalysts. Since the growth temperatures investigated are lower than the eutectic temperatures of these Si-metal alloys, VSS growth is expected and observed. Different temperatures and HCl flow rates have been tested with the aim of minimizing 2D growth which induces an important tapering of the NW. Finally, mechanical characterization of single NW has been carried out using an AFM method developed at the LTM. It consists in measuring the deflection of an AFM tip while performing approach-retract curves at various positions along the length of a cantilevered NW. This approach allows the measurement of as-grown single NW's Young modulus and spring constant, and alleviates uncertainties inherent in single point measurement.