Mass spectrometry studies of immunoglobulins

Immunoglobulin (Ig) proteins, also known as antibodies, are important molecules with great variability in their amino acid sequences. Aberrantly overproduced monoclonal Ig light chain (LC) proteins may aggregate into a β-sheet featured structure, and deposit in the extracellular space; this pathologic process, called primary amyloidosis or Ig LC amyloidosis (AL) causes problems to multiple organs during the course of the disease. Post-translational modifications (PTMs), which remain to be explored, are likely an important factor affecting the formation of AL fibrils. In addition, therapeutic monoclonal antibodies (mAbs) are widely employed because of their high specificity and low side effects. Using plants as the expression platform is commercially attractive although this approach has been hampered by low protein expression yield and undesired glycosylation patterns. The investigations detailed in this dissertation focus on the analyses of Ig proteins derived from several human and plant sources. A method combining 2D SDS-PAGE separation and mass spectrometry (MS) analysis was used for de novo sequencing of Ig in a fat biopsy for which the corresponding DNA was unavailable, and for characterizing the LC proteins found in autopsied kidney, serum and urine samples from patients with AL amyloidosis whose LC-DNA was sequenced. The PTMs of each LC were extensively characterized with different enzymes and various tandem MS techniques including collision-induced dissociation (CID), higher-energy collisional dissociation (HCD) and electron transfer dissociation (ECD). PTMs observed include truncations, mono-/di-chlorination of the tyrosine residues and a nitrile group formed from the primary amine on lysine side chains. All these may play critical roles in the fibrillogenesis and/or the disease pathogenesis. Experimental evidence supports the hypothesis that the proteolytic processing of amyloidogenic LCs occurs after deposition in the organ. Characterization of a plant-derived HSV8 mAb was accomplished using high-performance liquid chromatography separation and gel display followed by various MS methods. Three N-terminal and one C-terminal truncations were found. The N-glycan moiety attached to the heavy chain was also analyzed. The MS method established helps to elucidate important structural information on therapeutic mAbs in complex mixtures, potentially contributing to optimization of plant systems that may produce more stable mAbs

Efficient Processing of k Nearest Neighbor Joins using MapReduce

k nearest neighbor join (kNN join), designed to find k nearest neighbors from a dataset S for every object in another dataset R, is a primitive operation widely adopted by many data mining applications. As a combination of the k nearest neighbor query and the join operation, kNN join is an expensive operation. Given the increasing volume of data, it is difficult to perform a kNN join on a centralized machine efficiently. In this paper, we investigate how to perform kNN join using MapReduce which is a well-accepted framework for data-intensive applications over clusters of computers. In brief, the mappers cluster objects into groups; the reducers perform the kNN join on each group of objects separately. We design an effective mapping mechanism that exploits pruning rules for distance filtering, and hence reduces both the shuffling and computational costs. To reduce the shuffling cost, we propose two approximate algorithms to minimize the number of replicas. Extensive experiments on our in-house cluster demonstrate that our proposed methods are efficient, robust and scalable.Comment: VLDB201

On solvability of finite groups with some ssss-supplemented subgroups

summary:A subgroup $H$ of a finite group $G$ is said to be $ss$-supplemented in $G$ if there exists a subgroup $K$ of $G$ such that $G=HK$ and $H\cap K$ is $s$-permutable in $K$. In this paper, we first give an example to show that the conjecture in A. A. Heliel's paper (2014) has negative solutions. Next, we prove that a finite group $G$ is solvable if every subgroup of odd prime order of $G$ is $ss$-supplemented in $G$, and that $G$ is solvable if and only if every Sylow subgroup of odd order of $G$ is $ss$-supplemented in $G$. These results improve and extend recent and classical results in the literature