The genetics behind the progression of myelodysplasia to secondary acute myeloid leukemia (sAML) is poorly understood. In this study, we profiled somatic mutations and their dynamics using next ...generation sequencing on serial samples from a total of 124 patients, consisting of a 31 patient discovery cohort and 93 patients from two validation cohorts. Whole-exome analysis on the discovery cohort revealed that 29 of 31 patients carry mutations related to at least one of eight commonly mutated pathways in AML. Mutations in genes related to DNA methylation and splicing machinery were found in T-cell samples, which expand at the initial diagnosis of the myelodysplasia, suggesting their importance as early disease events. On the other hand, somatic variants associated with signaling pathways arise or their allelic burdens expand significantly during progression. Our results indicate a strong association between mutations in activated signaling pathways and sAML progression. Overall, we demonstrate that distinct categories of genetic lesions play roles at different stages of sAML in a generally fixed order.
Most types of cancers are made up of heterogeneous mixtures of genetically distinct subclones. In particular, acute myeloid leukemia (AML) has been shown to undergo substantial clonal evolution over ...the course of the disease. AML tends to harbor fewer mutations than solid tumors, making it challenging to infer clonal structure. Here, we present a 9-year, whole-exome sequencing study of a single case at 12 time points, from the initial diagnosis until a fourth relapse, including 6 remission samples in between. To the best of our knowledge, it covers the longest time span of any data set of its kind. We used these time series data to track the hierarchy and order of variant acquisition, and subsequently analyzed the evolution of somatic variants to infer clonal structure. From this, we postulate the development and extinction of subclones, as well as their anticorrelated expansion via varying drug responses. In particular, we show that new subclones started appearing after the first complete remission. The presence and absence of different subclones during remission and relapses implies differing drug responses among subclones. Our study shows that time series analysis contrasting remission and relapse periods provides a much more comprehensive view of clonal structure and evolution.
Evaluation of MCM-D technology for silicon strip detectors Eklund, L.; Affolder, A.; Casse, G. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
11/2010, Letnik:
623, Številka:
1
Journal Article
Recenzirano
Multi-chip Modules-Deposited (MCM-D) is a technology that can be applied to silicon strip modules and promises advantages in terms of integration complexity and material budget. This technology ...permits to integrate the front-end hybrid, pitch adaptor and wire bonds on the silicon sensor. The principle is to deposit alternating dielectric and metal layers directly on the silicon, where traces and vias are etched with high resolution to produce a PCB like structure.
This paper reports on a prototype MCM-D processing run of silicon strip wafers performed to evaluate suitability of the technology. This first run uses one dielectric layer, one metal layer, passivation and a final metallisation appropriate for wire-bonding. Connections are done through the first dielectric layer to the strips, the bias ring, bias resistors and guard rings. Hence the effects of the post-processing on the silicon sensor are evaluated measuring change in parameters such as I/V and C/V characteristics, inter-strip capacitance and resistance.
This paper describes the evaporative system used to cool the silicon detector structures of the inner detector sub-detectors of the ATLAS experiment at the CERN Large Hadron Collider. The motivation ...for an evaporative system, its design and construction are discussed. In detail the particular requirements of the ATLAS inner detector, technical choices and the qualification and manufacture of final components are addressed. Finally results of initial operational tests are reported. Although the entire system described, the paper focuses on the on-detector aspects. Details of the evaporative cooling plant will be discussed elsewhere.
The ATLAS experiment is preparing for the planned luminosity upgrade of the LHC (the super-luminous LHC or sLHC) with a programme of development for tracking able to withstand an order of greater ...magnitude radiation fluence and much greater hit occupancy rates than the current detector. This has led to the concept of an all-silicon tracker with an enhanced performance pixel-based inner region and short-strips for much of the higher radii. Both sub-systems employ many common technologies, including the proposed “stave” concept for integrated cooling and support. For the short-strip region, use of this integrated stave concept requires single-sided modules mounted on either side of a thin central lightweight support.
Each sensor is divided into four rows of 23.82
mm length strips; within each row, there are 1280 strips of 74.5μm pitch. Well over a hundred prototype sensors are being delivered by Hamamatsu Photonics (HPK) to Japan, Europe and the US.
We present results of the first 20 chip ABCN25 ASIC hybrids for these sensors, results of the first prototype 5120 strip module built with 40 ABCN25 read-out ASICs, and the status of the hybrids and modules being developed for the ATLAS tracker upgrade stave programme.
We present a study of a CMOS test sensor which has been designed, fabricated and characterised to investigate the parameters required for a binary readout electromagnetic calorimeter. The sensors ...were fabricated with several enhancements in addition to standard CMOS processing. Detailed simulations and experimental results of the performance of the sensor are presented. The sensor and pixels are shown to behave in accordance with expectations and the processing enhancements are found to be essential to achieve the performance required.
The TeraPixel Active Calorimeter (TPAC) sensor is a novel Monolithic Active Pixel Sensors (MAPS) device developed for use as the active layers of a large area, digital electromagnetic calorimeter ...(DECAL) at a future e super(+)e super(-) collider. Further applications, which include the tracking and vertex systems for future lepton colliders and LHC upgrades have been proposed and it is therefore essential to characterise the behaviour of the sensor for these applications. We present the first studies of radiation hardness testing of the TPAC sensor. The performance of the sensor has been evaluated after exposures up to 5 Mrad of 50 keV x-rays. Under realistic ILC operating conditions a maximum decrease in the signal to noise ratio of 8% (15%) was observed after 200 krad (5 Mrad) which is already sufficient for proposed applications in future e super(+)e super(-) colliders.
Monolithic active pixel sensors (MAPS) in a VLSI CMOS technology Turchetta, R; French, M; Manolopoulos, S ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
03/2003, Letnik:
501, Številka:
1
Journal Article
Recenzirano
Monolithic Active Pixel Sensors (MAPS) designed in a standard VLSI CMOS technology have recently been proposed as a compact pixel detector for the detection of high-energy charged particle in ...vertex/tracking applications. MAPS, also named CMOS sensors, are already extensively used in visible light applications. With respect to other competing imaging technologies, CMOS sensors have several potential advantages in terms of low cost, low power, lower noise at higher speed, random access of pixels which allows windowing of region of interest, ability to integrate several functions on the same chip. This brings altogether to the concept of ‘camera-on-a-chip’.
In this paper, we review the use of CMOS sensors for particle physics and we analyse their performances in term of the efficiency (fill factor), signal generation, noise, readout speed and sensor area. In most of high-energy physics applications, data reduction is needed in the sensor at an early stage of the data processing before transfer of the data to tape. Because of the large number of pixels, data reduction is needed on the sensor itself or just outside. This brings in stringent requirements on the temporal noise as well as to the sensor uniformity, expressed as a Fixed Pattern Noise (FPN).
A pixel architecture with an additional transistor is proposed. This architecture, coupled to correlated double sampling of the signal will allow cancellation of the two dominant noise sources, namely the reset or kTC noise and the FPN. A prototype has been designed in a standard 0.25
μm CMOS technology. It has also a structure for electrical calibration of the sensor. The prototype is functional and detailed tests are under way.
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