MSI-based mapping strategies in tumour-heterogeneity

Since the early 2000s, considerable innovations in MS technology and associated gene sequencing systems have enabled the "-omics" revolution. The data collected from multiple omics research can be combined to gain a better understanding of cancer's biological activity. Breast and ovarian cancer are among the most common cancers worldwide in women. Despite significant advances in diagnosis, treatment, and subtype identification, breast cancer remains the world's second leading cause of cancer-related deaths in women, with ovarian cancer ranking fifth. Tumour heterogeneity is a significant hurdle in cancer patient prognosis, response to therapy, and metastasis. As such, heterogeneity is one of the most significant and clinically relevant areas of cancer research nowadays. Metabolic reprogramming is a hallmark of malignancy that has been widely acknowledged in recent literature. Metabolic heterogeneity in tumours poses a challenge in developing therapies that exploit metabolic vulnerabilities. Consequently, it is crucial to approach tumour heterogeneity with an unlabeled yet spatially specific read-out of metabolic and genetic information. The advantage of DESI-MSI technology originates from its untargeted nature, which allows for the investigation of thousands of component distributions, at a micrometre scale, in a single experiment. Most notably, using a DESI-MSI clustering approach could potentially offer novel insights into metabolism, providing a method to characterise metabolically distinct sub-regions and subsequently delineate the underlying genetic drivers through genomic analyses. Hence, in this study, we aim to map the inter-and intra-tumour metabolic heterogeneity in breast and ovarian cancer by integrating multimodal MSI-based mapping strategies, comprising DESI and MALDI, with IMC (Imaging Mass Cytometry) analysis of the tumour section, using CyTOF, and high- throughput genetic characterisation of metabolically-distinct regions by transcriptomics. The multimodal analysis workflow was initially performed using sequential breast cancer Patient-Derived Xenografts (PDX) models and was expanded on primary tumour sections. Moreover, a newly developed DESI-MSI friendly, hydroxypropyl-methylcellulose and polyvinylpyrrolidone (HPMC/PVP) hydrogel-based embedding was successfully established to allow simultaneous preparation and analysis of numerous fresh frozen core-size biopsies in the same Tissue Microarray (TMA) block for the investigation of tumour heterogeneity. Additionally, a single section strategy was combined with DESI-MSI coupled to Laser Capture Microdissection (LCM) application to integrate gene expression analysis and Liquid Chromatography-Mass Spectrometry (LC-MS) on the same tissue segment. The developed single section methodology was then tested with multi-region collected ovarian tumours. DESI-MSI-guided spatial transcriptomics was performed for co-registration of different omics datasets on the same regions of interest (ROIs). This co-registration of various omics could unravel possible interactions between distinct metabolic profiles and specific genetic drivers that can lead to intra-tumour heterogeneity. Linking all these findings from MSI-based or guided various strategies allows for a transition from a qualitative approach to a conceptual understanding of the architecture of multiple molecular networks responsible for cellular metabolism in tumour heterogeneity.Open Acces

Fuel flexible power stations: Utilisation of ash co-products as additives for NOx emissions control

This work investigated the effects of different ash co-products on the combustion of solid fuels, in particular the fuel-nitrogen behaviour: The fuel-ash additive combinations investigated were: Firstly, biomass ashes added to bituminous coals, representative of those used in power stations; Secondly, a low reactivity coal; Thirdly, a high-N biomass (olive cake) was chosen as a high reactivity fuel and studied with a power-station pulverised coal fly ash as an additive. These five solid fuels have a wide fuel ratio FR (i.e. the ratio of fixed carbon to volatile matter content). The ash additives were a pulverised fly ash (PFA) and a furnace bottom ash (FBA) from wood pellet combustion in a UK power station. Fuels (with and without additives) were studied for nitrogen partitioning during (i) devolatilisation and for (ii) NOX formation during combustion, using two different electrically heated drop tube furnaces (DTF) operating at 1373 K. Devolatilisation was also studied via ballistic-heated thermogravimetric analysis (TGA). The extent of impact of additives on volatile yield under devolatilisation conditions was dependent on fuel ratio, high FR has the greatest increase in volatile release when co-feeding the additive. Under devolatilisation conditions, there is a correlation between volatile nitrogen and carbon conversion for all the fuels tested. Thus, additives liberate more volatile-nitrogen from the coals and also deliver enhanced carbon conversion. A mechanism is proposed whereby ultra-fine particles and vapours of reactive compounds from the additives interact with the reacting fuel/char particle and influence N-release during both devolatilisation and char burn-out. The enhanced conversion of fuel-nitrogen to volatile-nitrogen and the reduction of char-nitrogen can lead to reductions of NOX emissions in emissions-controlled furnaces. This approach could assist fuel-flexible power stations in achieving their NOX emission targets

Genetic framework of Neogene-Quaternary basin closure process in central Turkey

WOS: 000359000300005Central Turkey represents the only orogenic plateau in the Mediterranean region. Also, the largest closed drainage basin and the largest intracontinental basin of Turkey, the Lake Tuz Basin, is located in this region. Results from a three-dimensional (3-D) computer modeling study of the Lake Tuz Basin indicate a southward-deepening freshwater lake basin with great depth in the Mio-Pliocene, which regressed toward the north during the Plio-Quaternary into the shallow saline lake basin it is today. The spatio-temporal variations of Neogene and Quaternary deposits reflect the main effects of internal forces (isostasy>volcanism>faulting) that were caused by lithospheric slab breakoff and subsequent asthenospheric upwelling under central Turkey. Climatic change played a relatively minor role during these periods and was closely associated with the results of internal forces.AUBAP (Ankara University Scientific Research Projects) [09B4343017]We are grateful to I.O. Yilmaz, G. Seyitoglu, O.F. Gurer, B. Varol, Y.K. Kadioglu, A. Ates, F. Saroglu, and L. Royden for their contributions and fruitful discussions. The constructive reviews of E. Kirby, Y. Dilek, and T. Schildgen improved the manuscript significantly. This study was supported by the AUBAP (Ankara University Scientific Research Projects, Grant no: 09B4343017)

High-Q Adaptive Matching Network for Remote Powering of UHF RFIDs and Wireless Sensor Systems

Process and temperature independent RF front-end design is important for remotely powered RFID tags and wireless sensor systems. Run-to-run process variations can impact the remote powering performance and therefore read range of aforementioned systems. We introduce analysis and propose a design methodology for high-Q switched capacitor matching network for remote powering. The method is demonstrated with a differential drive rectifier topology with -14 dBm of input power at 900 MHz UHF band. Simulation results show the improvement on delivered power up to 42% and extension of the read range of the sensor system up to 19% with utilization of the proposed work

The Pressure Effect on Glass Formation and Cluster Structure Evolution during Cooling Process of PdNi Alloy: A Molecular Dynamics Study

Based on the embedded atom method a molecular dynamics simulation technique has been used to study the glass formation and atomic short range order in Pd-Ni binary alloy. By using radial distribution functions and Honeycutt-Andersen pair analysis methods, the structural development of this alloy is studied by quenching from the liquid at two different cooling rates and under 0 and 5 GPa pressures. The results show that the variation of local atomic bonded pairs is of great importance to understand the glass formation process and increase of the number of the ideal icosahedra under high pressure contributes to more ideal glass formation of model alloy

Simulation oriented rectenna design methodology for remote powering of wireless sensor systems

Abstract — Performance of wireless sensor systems are eval-uated on the basis of the quality of data communication and efficiency of power transmission. This work presents the design methodology of a miniaturized tag antenna for remote powering of wireless sensor systems at 2.45 GHz ISM band. Accurate simu-lations of the rectifier input impedance aimed at the maximization of transmitted power are presented. Simulation results combined with simple transmitting antenna scattering parameters and cable loss measurements provide straightforward characterization of the fabricated tag antenna. The experimental measurements on a 12x10mm miniaturized antenna designed with the proposed approach show a gain of-5.9 dB close by 0.8 dB to the simulation results. I

Outcome of Dentigerous Cysts Treated with Marsupialization

WOS: 000274558000014PubMed ID: 20297710Objective: The aim of this study was to evaluate the results of dentigerous cysts in children treated with marsupialization. Study design: 35 dentigerous cysts from 35 children treated with marsupialization were included in the study. The age of the children ranged from 8 to 13 years old. Results: The findings of our study showed that the outcome of dentigerous cysts treated with marsupialization is successful resulting with the eruption of teeth and regeneration of bone. Accordingly a successful outcome was achieved either with or without the help of an orthodontic treatment. Postoperative follow-ups were un-eventful in all patients during a 5 year period. Conclusion: The results of the present study demonstrate that marsupialization may be a better choice of treatment for dentigerous cysts in children rather than the standard treatment