Anion-Peptide Adduct Formation and Decomposition As Studied by Fourier Transform Ion Cyclotron Resonance (FT-ICR) Mass Spectrometry

A new “best match” match model has been developed to account for adduct formation on multiply charged peptides observed in negative ion electrospray mass spectrometry. To obtain a stable adduct, the model necessitates an approximate matching of apparent gas-phase basicity (GBapp) of a given proton bearing site on the peptide with the gas-phase basicity (GB) of the anion attaching at that site. Evidence supporting the model is derived from the fact that singly charged adducts were only observed for lower GB anions: HSO4-, I-, CF3COO-. Ions that have medium GBs (NO3-, Br-, H2PO4-) only form adducts having -2 charge states, whereas Cl- (higher GB) can form adducts having -3 charge states. Hydrogen bonds are the main interactions pertinent to the “Best Match” model, however, ion-ion interactions formed between peptides ([Glu]Fibrinopeptide B, Angiotensin I or [Asn1,Val5]-Angiotensin II) and low GB anions (ClO4- or HSO4-) have been established by CID-MS/MS. Evidence for ion-ion interactions comes especially from product ions formed during the first dissociation step, where, in addition to the expected loss of the anion or neutral acid, other product ions that require covalent bond cleavage (i.e., H2O or NH3 loss) are also observed. In this study, the “Best Match” model is further supported by the decomposition behavior of adducts formed when Na+/H+ exchange has occurred on peptides. Na+/H+ exchanges were found to occur preferentially at higher acidity sites. Without any Na+/H+ exchange, F- and CH3COO- can hardly form observable adducts with [Glu]Fibrinopeptide B. However, after multiple Na+/H+ exchanges, F- and CH3COO- do form stable adducts. This phenomenon can be rationalized by considering that Na+ cations serve to “block” the highly acidic sites, thereby forcing them to remain overall neutral. This leaves the less acidic protons available to match with higher GB anions. According to the best match model, high GB anions will match with high GBapp sites on the peptide, whereas low GB anions will match with low GBapp peptide sites. High charge states readily augment GBapp of the peptide (through-space effect). Na+/H+ exchanges substantially decrease GBapp by neutralizing charged sites, while slightly increasing intrinsic GBs by the inductive effect

Chunk-Based Bi-Scale Decoder for Neural Machine Translation

In typical neural machine translation~(NMT), the decoder generates a sentence word by word, packing all linguistic granularities in the same time-scale of RNN. In this paper, we propose a new type of decoder for NMT, which splits the decode state into two parts and updates them in two different time-scales. Specifically, we first predict a chunk time-scale state for phrasal modeling, on top of which multiple word time-scale states are generated. In this way, the target sentence is translated hierarchically from chunks to words, with information in different granularities being leveraged. Experiments show that our proposed model significantly improves the translation performance over the state-of-the-art NMT model.Comment: Accepted as a short paper by ACL 201

Accurate Multi-physics Numerical Analysis of Particle Preconcentration Based on Ion Concentration Polarization

This paper studies mechanism of preconcentration of charged particles in a straight micro-channel embedded with permselective membranes, by numerically solving coupled transport equations of ions, charged particles and solvent fluid without any simplifying assumptions. It is demonstrated that trapping and preconcentration of charged particles are determined by the interplay between drag force from the electroosmotic fluid flow and the electrophoretic force applied trough the electric field. Several insightful characteristics are revealed, including the diverse dynamics of co-ions and counter ions, replacement of co-ions by focused particles, lowered ion concentrations in particle enriched zone, and enhanced electroosmotic pumping effect etc. Conditions for particles that may be concentrated are identified in terms of charges, sizes and electrophoretic mobilities of particles and co-ions. Dependences of enrichment factor on cross-membrane voltage, initial particle concentration and buffer ion concentrations are analyzed and the underlying reasons are elaborated. Finally, post priori a condition for validity of decoupled simulation model is given based on charges carried by focused charge particles and that by buffer co-ions. These results provide important guidance in the design and optimization of nanofluidic preconcentration and other related devices.Comment: 18 pages, 11 firgure

Roles of TGFβ and FGF signals during growth and differentiation of mouse lens epithelial cell in vitro.

Transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signaling pathways play important roles in the proliferation and differentiation of lens epithelial cells (LECs) during development. Low dosage bFGF promotes cell proliferation while high dosage induces differentiation. TGFβ signaling regulates LEC proliferation and differentiation as well, but also promotes epithelial-mesenchymal transitions that lead to cataracts. Thus far, it has been difficult to recapitulate the features of germinative LECs in vitro. Here, we have established a LEC culture protocol that uses SB431542 (SB) compound to inhibit TGFβ/Smad activation, and found that SB treatment promoted mouse LEC proliferation, maintained LECs' morphology and distinct markers including N-cadherin, c-Maf, Prox1, and αA-, αB-, and β-crystallins. In contrast, low-dosage bFGF was unable to sustain those markers and, combined with SB, altered LECs' morphology and β-crystallin expression. We further found that Matrigel substrate coatings greatly increased cell proliferation and uniquely affected β-crystallin expression. Cultured LECs retained the ability to differentiate into γ-crystallin-positive lentoids by high-dosage bFGF treatment. Thus, a suppression of TGFβ/Smad signaling in vitro is critical to maintaining characteristic features of mouse LECs, especially expression of the key transcription factors c-Maf and Prox1