Mass spectrometry based characterization of Hb Beckman variant in a falsely elevated HbA(1c) sample

Glycated hemoglobin (HbA(1c)) is a `gold standard' biomarker for assessing the glycemic index of an individual. HbA(1c) is formed due to nonenzymatic glycosylation at N-terminal valine residue of the P-globin chain. Cation exchange based high performance liquid chromatography (CE HPLC) is mostly used to quantify HbA(1c), in blood sample. A few genetic variants of hemoglobin and post-translationally modified variants of hemoglobin interfere with CE HPLC-based quantification,. resulting in its false positive estimation. Using mass spectrometry, we analyzed a blood sample with abnormally high HbA(1c) (52.1%) in the CE HPLC method. The observed HbA(1c) did not corroborate the blood glucose level of the patient. A mass spectrometry based bottom up proteomics approach, intact globin chain mass analysis, and chemical modification of the proteolytic peptides identified the presence of Hb Beckman, a genetic variant of hemoglobin, in the experimental sample. A similar surface area to charge ratio between HbA(1c) and Hb Beckman might have resulted in the coelution of the variant with HbA(1c) in CE HPLC. Therefore, in the screening of diabetes mellitus through the estimation of HbA(1c), it is important to look for genetic variants of hemoglobin in samples that show abnormally high glycemic index, and HbA(1c) must be estimated using an alternative method. (C) 2015 Elsevier Inc. All rights reserved.

A PRACTICAL PROCEDURE TO ESTIMATE THE BEARING CAPACITY OF FOOTINGS ON SAND-APPLICATION TO 87 CASE STUDIES

Following the recent work of the authors in development and numerical verification of a new kinematic approach of the limit analysis for surface footings on non-associative materials, a practical procedure is proposed to utilize the theory. It is known that both the peak friction angle and dilation angle depend on the sand density as well as the stress level, which was not the concern of the former work. In the current work, a practical procedure is established to provide a better estimate of the bearing capacity of surface footings on sand which is often non-associative. This practical procedure is based on the results obtained theoretically and requires the density index and the critical state friction angle of the sand. The proposed practical procedure is a simple iterative computational procedure which relates the density index of the sand, stress level, dilation angle, peak friction angle and eventually the bearing capacity. The procedure is described and verified among available footing load test data.