Comprehensive diagnostics of acute myeloid leukemia by whole transcriptome RNA sequencing

Acute myeloid leukemia (AML) is caused by genetic aberrations that also govern the prognosis of patients and guide risk-adapted and targeted therapy. Genetic aberrations in AML are structurally diverse and currently detected by different diagnostic assays. This study sought to establish whole transcriptome RNA sequencing as single, comprehensive, and flexible platform for AML diagnostics. We developed HAMLET (Human AML Expedited Transcriptomics) as bioinformatics pipeline for simultaneous detection of fusion genes, small variants, tandem duplications, and gene expression with all information assembled in an annotated, user-friendly output file. Whole transcriptome RNA sequencing was performed on 100 AML cases and HAMLET results were validated by reference assays and targeted resequencing. The data showed that HAMLET accurately detected all fusion genes and overexpression of EVI1 irrespective of 3q26 aberrations. In addition, small variants in 13 genes that are often mutated in AML were called with 99.2% sensitivity and 100% specificity, and tandem duplications in FLT3 and KMT2A were detected by a novel algorithm based on soft-clipped reads with 100% sensitivity and 97.1% specificity. In conclusion, HAMLET has the potential to provide accurate comprehensive diagnostic information relevant for AML classification, risk assessment and targeted therapy on a single technology platform

Microchannel cooling for the LHCb VELO Upgrade I

The LHCb VELO Upgrade I, currently being installed for the 2022 start of LHC Run 3, uses silicon microchannel coolers with internally circulating bi-phase \cotwo for thermal control of hybrid pixel modules operating in vacuum. This is the largest scale application of this technology to date. Production of the microchannel coolers was completed in July 2019 and the assembly into cooling structures was completed in September 2021. This paper describes the R\&D path supporting the microchannel production and assembly and the motivation for the design choices. The microchannel coolers have excellent thermal peformance, low and uniform mass, no thermal expansion mismatch with the ASICs and are radiation hard. The fluidic and thermal performance is presented.Comment: 31 pages, 27 figure

Redesign of the VELO Thermal Control System Forfuture Detector Development

The Detector Technologies group at CERN has developed a Two-Phase Accumulator Controlled Loop (2PACL) test system for future detector development, using reused hardware from the LHCb Vertex Locator (VELO) Thermal Control System. The fluid, electrical and control systems have been redesigned and simplified by removing redundant components because it is no longer a critical system. The fluid cycle was updated to allow both 2PACL and integrated 2PACL cycles to be run and the chiller was replaced with an air-cooled unit using hot gas bypass to achieve a high turndown ratio. The electrical systems were upgraded with new hardware to improve usability and practicality. The control system logic is being developed with the CERN’s Unified Industrial Control System (UNICOS) framework. This paper presents thedetails of the design and implementation

CO2 cooling challenges at CERN for the future phase 2 upgrade program

At CERN, evaporative CO2 is the baseline cooling solution for the thermal management of the phase 2 silicon detectors. Since 2008 CO2 cooling is used in 3 detectors with capacities ranging 1 to 15 kW at -30°C. A special pumped cycle was developed to guarantee accurate temperature control under all operational conditions. The challenges for the upgrade are: the large increase of the cooling power (250 - 450 kW), the large number of parallel operating evaporators (~1000x), the low evaporative temperature (-45°C). and the implementation of a primary R744 transcritical system. Implementing this R744 primary cooling solution will make the future detector cooling to work fully with natural working fluids (R744 and R718). This paper describes the design and prototyping phase of the system with surface storage and the new primary R744 system, which bridges the industrial applications of R744 refrigeration to the highly demanding performances of high energy physics experiments

CO2_2 cooling experience (LHCb)

The thermal control system of the LHCb VErtex LOcator (VELO) is a two-phase C0$_2$ cooling system based on the 2-Phase Accumulator Controlled Loop (2PACL) method. Liquid carbon dioxide is mechanically pumped in a closed loop, chilled by a water-cooled freon chiller and evaporated in the VELO detector. The main goal of the system is the permanent cooling of the VELO silicon sensors and of the heat producing front-end electronics inside a vacuum environment. This paper describes the design and the performance of the system. First results obtained during commissioning are also presented

Adiabatic two-phase pressure drop of carbon dioxide in different channel orientations

Adiabatic pressure drop measurements of two-phase Carbon Dioxide (CO$_2$) have been carried out in horizontal, vertical upward and downward direction with a dedicated test facility at the European Organization for Nuclear Research (CERN). A database of more than 1100 measurements, consisting of 512 data points in horizontal and 295 data points for each vertical up- and downflow respectively, has been compiled within this study. The experiments cover saturation temperatures from − 25 °C⩽$T_{\textrm{sat}}$⩽ +5 °C, mass velocities from 100 kg m$^{-2}$ s$^{-1}$⩽$G$⩽ 450 kg m$^{-2}$ s$^{-1}$ and are carried out in test sections with an inner diameter of 8 mm. The analysis of the pressure drop signals reveals that pressure fluctuations are increasing around the slug flow regime and the oscillation effects get magnified in vertical direction. The measurements in horizontal direction are compared to 18 frictional pressure drop models. For the comparison of the vertical data, 21 void fraction correlations accounting for the static head have been combined with the frictional models. The data sets of the horizontal and vertical upflow measurements are well predicted by several pressure drop models with an acceptable statistical significance. However, the prediction models perform less accurately for vertical downflow and it has been found that the static head is not well described by the void fraction correlations. In particular at low mass velocities, the effects of phase separation due to dominant buoyancy forces are not well incorporated by the void fraction models considered. In addition to the comparison of the entire data sets, subdivided analyses accounting for the flow patterns are provided within the present work

Flow pattern observations and flow pattern map for adiabatic two-phase flow of carbon dioxide in vertical upward and downward direction

A test facility to investigate flow pattern transitions of vertical two-phase flow of CO2 has been built within the scope of the high-luminosity detector upgrades at the European Organization for Nuclear Research (CERN). Adiabatic flow pattern observations for both vertical up- and downflow are recorded with high-speed imaging in tubes of 8 mm inner diameter, with saturation temperatures in the range of −25◦C to +5◦C and mass velocities ranging from 100 kg m$^{-2}$ s$^{-1}$ to 450 kg m$^{-2}$ s$^{-1}$. A database of 431 flow pattern observations in upward and 123 in downward direction has been compiled. The recorded data have been analysed with machine learning techniques and a previously trained Frame- and Flow-Regime-Classifier is used for the flow regime classification. The observed two-phase flow pattern transitions did not match the transition lines of existing flow pattern maps. As a consequence, new transition lines for the bubbly-to-slug, slug-to-churn and churn-toannular transitions have been developed for both vertical upflow and downflow respectively and condensed into new flow pattern maps. It is concluded, that the flow regime transitions are strongly depended on vapour quality, mass velocity, the flow direction and the fluid properties. Compared to horizontal flow, a dryout region is not observed and the liquid film of the annular flow regime dries out symmetrically at vapour qualities close to $x = 1$

Heat transfer of flow boiling carbon dioxide in vertical upward direction

Heat transfer measurements of flow boiling Carbon Dioxide (CO$_2$) in vertical upward direction have been carried out with a dedicated test facility at the European Organization for Nuclear Research (CERN). The investigation covers saturation temperatures within a range of $-25 \degree \textrm{C} \leq T_{\mathrm{sat}} +5 \degree \textrm{C}$, mass velocities from 100kg m$^{-2}$ s$^{-1}$ $\leq G \leq$ 450 kg m$^{-2}$ s$^{-1}$ and heat fluxes of 5.3 kW m$^{-2}$ and 11.4 kW m$^{-2}$. The experiments have been conducted in a vertical upward evaporator of 8 mm inner diameter and 8 m length and a database of more than 1900 measurements has been compiled within the present study. The heat transfer mechanism is dominated by the nucleate boiling contribution and dryout is observed as a function of saturation temperature, mass velocity and heat flux. A correlation is proposed to predict the dryout inception within the experimental range where the onset of dryout has been observed. The results suggest that most commonly used heat transfer prediction models underpredict the heat transfer mechanisms of CO$_2$. Moreover, the heat transfer coefficients of CO$_2$ increase in vertical upward direction, compared to the data of horizontal studies. For that reason, a vertical multiplier is suggested to capture the trends of vertical upflow with two existing prediction models