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The 2-hydroxyglutarate (2-HG) has been reported to result from mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes and to function as an "oncometabolite." To evaluate the clinical significance of serum 2-HG levels in hematologic malignancies, acute myeloid leukemia (AML) in particular, we analyzed this metabolite in distinct types of human leukemia and lymphoma and established the range of serum 2-HG in appropriate normal control individuals by using gas chromatograph-time-of-flight mass spectrometry. Aberrant serum 2-HG pattern was detected in the multicenter group of AML, with 62 of 367 (17%) patients having 2-HG levels above the cutoff value (2.01, log2-transformed from 4.03 µg/mL). IDH1/2 mutations occurred in 27 of 31 (87%) AML cases with very high 2-HG, but were observed only in 9 of 31 (29%) patients with moderately high 2-HG, suggesting other genetic or biochemical events may exist in causing 2-HG elevation. Indeed, glutamine-related metabolites exhibited a pattern in favor of 2-HG synthesis in the high 2-HG group. In AML patients with cytogenetically normal AML (n = 234), high 2-HG represented a negative prognostic factor in both overall survival and event-free survival. Univariate and multivariate analyses confirmed high serum 2-HG as a strong prognostic predictor independent of other clinical and molecular features. We also demonstrated distinct gene-expression/DNA methylation profiles in AML blasts with high 2-HG compared with those with normal ones, supporting a role that 2-HG plays in leukemogenesis. [ABSTRACT FROM AUTHOR]

A novel approach is proposed to identify the arrival time of overlapping ultrasonic echoes in time-of-flight diffraction (TOFD) flaw detection. The nonlinear and nonstationary ultrasonic signal is decomposed using empirical mode decomposition method to obtain intrinsic mode functions, which are used for signal reconstruction. By applying Hilbert transform to the reconstructed signal, the arrival time of each echo can be clearly identified. The efficiency and feasibility of this approach in enhancing the time resolution of ultrasonic signal are validated by simulation and experiment, where 98% of flaws in 12-, 10-, and 8-mm-thickness pipelines can be identified with an average accuracy of 0.2 mm. The blind area of TOFD has been reduced to 2.5 mm under the surface. The frequency and angle of the probe pair have little influence on the identification. [ABSTRACT FROM AUTHOR]

The multiteraelectronvolt γ-rays from the galactic center (GC) have a cutoff at tens of teraelectronvolts, whereas the diffuse emission has no such cutoff, which is regarded as an indication of petaelectronvolt proton acceleration by the HESS experiment. It is important to understand the inconsistency and study the possibility that petaelectronvolt cosmic-ray acceleration could account for the apparently contradictory point and diffuse γ-ray spectra. In this work, we propose that the cosmic rays are accelerated up to greater than petaelectronvolts in the GC. The interaction between cosmic rays and molecular clouds is responsible for the multiteraelectronvolt γ-ray emissions from both the point and diffuse sources today. Enhanced by the small volume filling factor (VFF) of the clumpy structure, the absorption of the γ-rays leads to a sharp cutoff spectrum at tens of teraelectronvolts produced in the GC. Away from the GC, the VFF grows, and the absorption enhancement becomes negligible. As a result, the spectra of γ-ray emissions for both point and diffuse sources can be successfully reproduced under such a self-consistent picture. In addition, a “surviving tail” at ∼100 TeV is expected from the point source, which can be observed by future projects CTA and LHAASO. Neutrinos are simultaneously produced during proton-proton (PP) collision. With 5–10 years of observations, the KM3Net experiment will be able to detect the petaelectronvolt source according to our calculation. [ABSTRACT FROM AUTHOR]