Knowledge of intrinsic tumor heterogeneity is vital for understanding of tumor progression mechanisms as well as for providing efficient treatments. In situ proteomic profiling of tumors is a ...powerful technology with potential to enhance our understanding of tumor biology, but sources of variability due to patient and tumor heterogeneity are poorly understood and are the topic of this investigation. Clarification of variability within case and between cases is also important for designing future studies. Direct protein profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a sensitive and powerful technology for obtaining hundreds of protein expression peaks from a thin tissue section. By combining robotic microspotting and laser capture microdissection with MALDI MS, we acquired multiple spectra per case to evaluate inter- and intra-case variability in human colorectal tumor and murine cecal carcinoma. We detected 256 peaks from 164 samples of 111 patients, which consisted of 55 normal colorectal mucosal samples, 24 adenomas, 71 primary carcinomas, and 14 hepatic metastases. In addition, we detected 291 peptide/protein peaks from 34 orthotopically transplanted murine cecal carcinomas and 14 hepatic metastases. In human colorectal samples, we observed that proteomic profiling in adenomas was more homogeneous across patients than in normal mucosa specimens (p=0.0008), but primary carcinoma exhibited greater heterogeneity than normal mucosa and adenomas (both p<0.0001). Murine cecal carcinomas were homogeneous within and between carcinomas, while their hepatic metastases tended toward greater intra-tumor differences (p<0.0001). Inter- and intra-case variability was approximately equal for many protein peaks. Acquiring up to 5 subsamples per case could reduce the total number of cases required, but further reduction from additional subsampling was modest unless intra-case variability comprises a greater proportion of total variation (e.g. >70%). In summary, this study characterizes intra- and inter-case variability of high-throughput protein expression in colorectal tumors, and provides guidance for the sample numbers required for in situ proteomic studies.
Evolutionary transfer multiobjective optimization (ETMO) has been becoming a hot research topic in the field of evolutionary computation, which is based on the fact that knowledge learning and ...transfer across the related optimization exercises can improve the efficiency of others. Besides, the potential for transfer optimization is deemed invaluable from the standpoint of human-like problem-solving capabilities where knowledge gather and reuse are instinctive. To promote the research on ETMO, benchmark problems are of great importance to ETMO algorithm analysis, which helps designers or practitioners to understand the merit and demerit better of ETMO algorithms. Therefore, a total number of 40 benchmark functions are proposed in this report, covering diverse types and properties in the case of knowledge transfer, such as various formulation models, various PS geometries and PF shapes, large-scale of variables, dynamically changed environment, and so on. All the benchmark functions have been implemented in JAVA code, which can be downloaded on the following website: https://github.com/songbai-liu/etmo.
The China Dark Matter Experiment (CDEX) is located at the China Jinping underground laboratory (CJPL) and aims to directly detect the WIMP flux with high sensitivity in the low mass region. Here we ...present a study of the predicted photon and electron backgrounds including the background contribution of the structure materials of the germanium detector, the passive shielding materials, and the intrinsic radioactivity of the liquid argon that serves as an anti-Compton active shielding detector. A detailed geometry is modeled and the background contribution has been simulated based on the measured radioactivities of all possible components within the GEANT4 program. Then the photon and electron background level in the energy region of interest (<10^-2 events kg-1 day-1 keV-1 (cpkkd)) is predicted based on Monte Carlo simulations. The simulated result is consistent with the design goal of CDEX-10 experiment, 0.1 cpkkd, which shows that the active and passive shield design of CDEX-10 is effective and feasible.
The CDEX Collaboration has been established for direct detection of light dark matter particles, using ultra-low energy threshold p-type point-contact germanium detectors, in China JinPing ...underground Laboratory (CJPL). The first 1 kg point-contact germanium detector with a sub-keV energy threshold has been tested in a passive shielding system located in CJPL. The outputs from both the point-contact p+ electrode and the outside n+ electrode make it possible to scan the lower energy range of less than 1 keV and at the same time to detect the higher energy range up to 3 MeV. The outputs from both p+ and n+ electrode may also provide a more powerful method for signal discrimination for dark matter experiment. Some key parameters, including energy resolution, dead time, decay times of internal X-rays, and system stability, have been tested and measured. The results show that the 1 kg point-contact germanium detector, together with its shielding system and electronics, can run smoothly with good performances. This detector system will be deployed for dark matter search experiments.
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