In vivo bioluminescence imaging using orthotopic xenografts towards patient's derived-xenograft Medulloblastoma models

BACKGROUND: Medulloblastoma is a cerebellar neoplasia of the central nervous system. Four molecular subgrups have been identified (MBWNT, MBSHH, MBgroup3 and MBgroup4) with distinct genetics and clinical outcome. Among these, MBgroup3-4 are highly metastatic with the worst prognosis. The current standard therapy includes surgery, radiation and chemotherapy. Thus, specific treatments adapted to cure those different molecular subgroups are needed. The use of orthotopic xenograft models, together with the non-invasive in vivo biolumiscence imaging (BLI) technology, is emerging during preclinical studies to test novel therapeutics for medulloblastoma treatment. METHODS: Orthotopic MB xenografts were performed by injection of Daoy-luc cells, that had been previously infected with lentiviral particles to stably express luciferase gene, into the fourth right ventricle of the cerebellum of ten nude mice. For the implantation, specific stereotactic coordinates were used. Seven days after the implantation the mice were imaged by acquisitions of bioluminescence imaging (BLI) using IVIS 3D Illumina Imaging System (Xenogen). Tumor growth was evaluated by quantifying the bioluminescence signals using the integrated fluxes of photons within each area of interest using the Living Images Software Package 3.2 (Xenogen-Perkin Elmer). Finally, histological analysis using hematoxylin-eosin staining was performed to confirm the presence of tumorigenic cells into the cerebellum of the mice. RESULTS: We describe a method to use the in vivo bioluminescent imaging (BLI) showing the potential to be used to investigate the potential antitumorigenic effects of a drug for in vivo medulloblastoma treatment. We also discuss other studies in which this technology has been applied to obtain a more comprehensive knowledge of medulloblastoma using orthotopic xenograft mouse models. CONCLUSIONS: There is a need to develop patient's derived-xenograft (PDX) model systems to test novel drugs for medulloblastoma treatment within each molecular sub-groups with a higher predictive value. Here we show how this technology should be applied with hopes on generations of new treatments to be applied then in human

MicroRNAs and Cancer Stem Cells in Medulloblastoma

In this chapter, we are describing the biology of medulloblastoma influenced by several genes/pathways which concur to its pathogenesis. Of note, several levels of regulation are mediated by miRNAs functions, which we dissect their “state of art” to underline their crucial roles on controlling cancer development. In brain tumours, literatures data, are supporting the values of Cancer Stem Cells (tumor propagating cells) and their functions for tumour recurrence for future therapeutic treatments. Thus, we link the potential use of miRNAs as “shuttle” to impair Cancer Stem Cells in medulloblastoma

Altering gait variability with an ankle exoskeleton

Exoskeletons can influence human gait. A healthy gait is characterized by a certain amount of variability compared to a non-healthy gait that has more inherent variability; however which exoskeleton assistance parameters are necessary to avoid increasing gait variability or to potentially lower gait variability below that of unassisted walking are unknown. This study investigated the interaction effects of exoskeleton timing and power on gait variability. Ten healthy participants walked on a treadmill with bilateral ankle-foot exoskeletons under ten conditions with different timing (varied from 36% to 54% of the stride) and power (varied from 0.2 to 0.5 W∙kg-1) combinations. We used the largest Lyapunov exponent (LyE) and maximum Floquet multiplier (FM) to evaluate the stride-to-stride fluctuations of the kinematic time series. We found the lowest LyE at the ankle and a significant reduction versus powered-off with exoskeleton power (summed for both legs) of 0.45 W∙kg-1 and actuation timing at 48% of the stride cycle. At the knee, a significant positive effect of power and a negative interaction effect of power and timing were found for LyE. We found significant positive interaction effects of the square of timing and power for LyE at the knee and hip joints. In contrast, the FM at the ankle increased with increasing power and later timing. We found a significant negative effect of power and a positive interaction effect of power and timing for FM at the knee and no significant effects of any of the exoskeleton parameters for FM at the hip. The ability of the exoskeleton to reduce the LyE at the ankle joint offers new possibilities in terms of altering gait variability, which could have applications for using exoskeletons as rehabilitation devices. Further efforts could examine if it is possible to simultaneously reduce the LyE and FM at one or more lower limb joints

Altering gait variability with an ankle exoskeleton

Exoskeletons can influence human gait. A healthy gait is characterized by a certain amount of variability compared to a non-healthy gait that has more inherent variability; however which exoskeleton assistance parameters are necessary to avoid increasing gait variability or to potentially lower gait variability below that of unassisted walking are unknown. This study investigated the interaction effects of exoskeleton timing and power on gait variability. Ten healthy participants walked on a treadmill with bilateral ankle-foot exoskeletons under ten conditions with different timing (varied from 36% to 54% of the stride) and power (varied from 0.2 to 0.5 W∙kg-1) combinations. We used the largest Lyapunov exponent (LyE) and maximum Floquet multiplier (FM) to evaluate the stride-to-stride fluctuations of the kinematic time series. We found the lowest LyE at the ankle and a significant reduction versus powered-off with exoskeleton power (summed for both legs) of 0.45 W∙kg-1 and actuation timing at 48% of the stride cycle. At the knee, a significant positive effect of power and a negative interaction effect of power and timing were found for LyE. We found significant positive interaction effects of the square of timing and power for LyE at the knee and hip joints. In contrast, the FM at the ankle increased with increasing power and later timing. We found a significant negative effect of power and a positive interaction effect of power and timing for FM at the knee and no significant effects of any of the exoskeleton parameters for FM at the hip. The ability of the exoskeleton to reduce the LyE at the ankle joint offers new possibilities in terms of altering gait variability, which could have applications for using exoskeletons as rehabilitation devices. Further efforts could examine if it is possible to simultaneously reduce the LyE and FM at one or more lower limb joints

Modeling of Indirect Evaporative Cooling Systems: A Review

Air-to-air indirect evaporative cooling (IEC) systems are particular heat exchangers that use the latent heat of evaporation of water to cool down an air stream, without increasing its specific humidity, thus guaranteeing adequate thermohygrometric conditions in the refrigerated environment with low energy consumption. Dew-point indirect evaporative cooling (DIEC) systems are based on the IEC technology, but they recirculate a part of the air taken from the room to be refrigerated, in order to possibly achieve a lower air temperature. IEC and DIEC systems are becoming increasingly common these years, as they can ensure a good efficiency, minimizing the environmental impact of the air-conditioning system. Consequently, it has been necessary to develop models, both analytical and numerical, to quickly and accurately design this type of system and to predict their performance. This paper presents a review of the analytical and numerical models developed specifically for IEC and DIEC systems, highlighting their method, main innovations and advantages, and possible limitations. From this analysis, it emerged that analytical models have been developed since the late 1990s and only few of them are suitable for DIEC heat exchangers, while numerical models for both IEC and DIEC systems are gaining popularity in recent years. Almost all the analyzed models have been validated by comparison with numerical and/or experimental data, showing a maximum discrepancy within 10% in the majority of the cases. However, the validations were performed for a few specific cases, so in real applications it might be difficult to associate the model boundary conditions and the heat exchangers operating conditions, such as nozzles orientations, plates materials, water flow rates, and configurations. Another common limitation concerns the modeling of some properties, as wettability factor and air density, which might affect the accuracy of the results

Design Optimization of Heat Wheels for Energy Recovery in HVAC Systems

Air to air heat exchangers play a crucial role in mechanical ventilation equipment, due to the potential primary energy savings both in case of refurbishment of existing buildings or in case of new ones. In particular, interest in heat wheels is increasing due to their low pressure drop and high effectiveness. In this paper a detailed optimization of design parameters of heat wheels is performed in order to maximize sensible effectiveness and to minimize pressure drop. The analysis is carried out through a one dimensional lumped parameters heat wheel model, which solves heat and mass transfer equations, and through appropriate correlations to estimate pressure drop. Simulation results have been compared with experimental data of a heat wheel tested in specific facilities, and good agreement is attained. The device optimization is performed through the variation of main design parameters, such as heat wheel length, channel base, height and thickness and for different operating conditions, namely the air face velocity and the revolution speed. It is shown that the best configurations are achieved with small channel thickness and, depending on the required sensible effectiveness, with appropriate values of wheel length and channel base and height

Experimental Characterization of the Wettability of Coated and Uncoated Plates for Indirect Evaporative Cooling Systems

Indirect Evaporative Cooling (IEC) is a very promising technology to substitute and/or integrate traditional air conditioning systems, due to its ability to provide cooling capacity with limited power consumption. Literature studies proved that a higher wettability of the IEC plates corresponds to better performance of the system. In this work, wettability of three different surfaces used for IEC systems plates—uncoated aluminum alloy (AL), standard epoxy coating (STD), and a hydrophilic lacquer (HPHI)—is studied and characterized in terms of static and dynamic contact angles. The static contact angle resulted to be the lowest for the HPHI surface (average 69°), intermediate for the STD surface (average 75°), and the highest for the AL surface (average 89°). The analysis of the dynamic contact angles showed that their transient behavior is similar for all the surfaces, and the advancing and receding contact angles obtained are consistent with the results of the static analysis. These results will be useful as input parameters in models aimed at predicting the IEC system performance, also using computational fluid dynamics

Indirect evaporative cooling systems: An experimental analysis in summer condition

Indirect evaporative coolers (IEC) are components that can be effectively installed in air handling units to increase energy efficiency of air conditioning systems. In particular, such devices can be used in summer conditions to reduce chiller load in both existing and new buildings. In this paper, an IEC system based on a cross flow heat exchanger has been tested, evaluating its cooling capacity in different operating conditions. Performance is evaluated in terms of wet bulb effectiveness, primary air temperature reduction and fraction of evaporated water. Results put in evidence that a significant cooling capacity can be achieved in many operating conditions. Therefore, IECs are a promising technology that can be effectively used to reduce primary energy consumption of conventional systems