Zhongzhou Chen

Flow-Induced Structural Transition in the β-Switch Region of Glycoprotein Ib

The impact of fluid flow on structure and dynamics of biomolecules has recently gained much attention. In this article, we present a molecular-dynamics algorithm that serves to generate stable water flow under constant temperature, for the study of flow-induced protein behavior. Flow simulations were performed on the 16-residue beta-switch region of platelet glycoprotein Ibalpha, for which crystal structures of its N-terminal domain alone and in complex with the A1 domain of von Willebrand factor have been solved. Comparison of the two structures reveals a conformational change in this region, which, upon complex formation, switches from an unstructured loop to a beta-hairpin. Interaction between glycoprotein Ibalpha and von Willebrand factor initiates platelet adhesion to injured vessel walls, and the adhesion is enhanced by blood flow. It has been hypothesized that the loop to beta-hairpin transition in glycoprotein Ib alpha is induced by flow before binding to von Willebrand factor. The simulations revealed clearly a flow-induced loop-->beta-hairpin transition. The transition is dominated by the entropy of the protein, and is seen to occur in two steps, namely a dihedral rotation step followed by a side-group packing step.

Theoretical and Computational Investigation of Flagellin Translocation and Bacterial Flagellum Growth

The bacterial flagellum is a self-assembling filament, which bacteria use for swimming. It is built from tens of thousands of flagellin monomers in a self-assembly process that involves translocation of the monomers through the flagellar interior, a channel, to the growing tip. Flagellum monomers are pumped into the filament at the base, move unfolded along the channel and then bind to the tip of the filament, thereby extending the growing flagellum. The flagellin translocation process, due to the flagellum maximum length of 20 μm, is an extreme example of protein transport through channels. Here, we derive a model for flagellin transport through the long confining channel, testing the key assumptions of the model through molecular dynamics simulations that also furnish system parameters needed for quantitative description. Together, mathematical model and molecular dynamics simulations explain why the growth rate of flagellar filaments decays exponentially with filament length and why flagellum growth ceases at a certain maximum length.

Using Multiple Accounts for Harvesting Solutions in MOOCs

The study presented in this paper deals with copying answers in MOOCs. Our findings show that a significant fraction of the certificate earners in the course that we studied have used what we call harvesting accounts to find correct answers that they later submitted in their main account, the account for which they earned a certificate. In total, around 2.5% of the users who earned a certificate in the course obtained the majority of their points by using this method, and around 10% of them used it to some extent. This paper has two main goals. The first is to define the phenomenon and demonstrate its severity. The second is characterizing key factors within the course that affect it, and suggesting possible remedies that are likely to decrease the amount of cheating. The immediate implication of this study is to MOOCs. However, we believe that the results generalize beyond MOOCs, since this strategy can be used in any learning environments that do not identify all registrants.

Flow-Induced β-Hairpin Folding of the Glycoprotein Ibα β-Switch

Flow-induced shear has been identified as a regulatory driving force in blood clotting. Shear induces beta-hairpin folding of the glycoprotein Ibalpha beta-switch which increases affinity for binding to the von Willebrand factor, a key step in blood clot formation and wound healing. Through 2.1-micros molecular dynamics simulations, we investigate the kinetics of flow-induced beta-hairpin folding. Simulations sampling different flow velocities reveal that under flow, beta-hairpin folding is initiated by hydrophobic collapse, followed by interstrand hydrogen-bond formation and turn formation. Adaptive biasing force simulations are employed to determine the free energy required for extending the unfolded beta-switch from a loop to an elongated state. Lattice and freely jointed chain models illustrate how the folding rate depends on the entropic and enthalpic energy, the latter controlled by flow. The results reveal that the free energy landscape of the beta-switch has two stable conformations imprinted on it, namely, loop and hairpin--with flow inducing a transition between the two.

Copying@Scale

This paper presents a detailed study of a form of academic dishonesty that involves the use of multiple accounts for harvesting solutions in a Massive Open Online Course (MOOC). It is termed CAMEO Copying Answers using Multiple Existence Online. A person using CAMEO sets up one or more harvesting accounts for collecting correct answers; these are then submitted in the users master account for credit.The study has three main goals: Determining the prevalence of CAMEO, studying its detailed characteristics, and inferring the motivation(s) for using it. For the physics course that we studied, about 10% of the certificate earners used this method to obtain more than 1% of their correct answers, and more than 3% of the certificate earners used it to obtain the majority (>50%) of their correct answers. We discuss two of the likely consequences of CAMEO: jeopardizing the value of MOOC certificates as academic credentials, and generating misleading conclusions in educational research. Based on our study, we suggest methods for reducing CAMEO. Although this study was conducted on a MOOC, CAMEO can be used in any learning environment that enables students to have multiple accounts. Studying the use of multiple accounts for harvesting solutions in a MOOCs.10% of the certificate earners used it to some extent; 3% for the majority of their points.Motivation is earning a certificate with less effort.This behavior is typically premediated, applied without attempting to solve the question legitimately first.Randomizing question parameters and delaying feedback reduce it significantly.

Researching for better instructional methods using AB experiments in MOOCs: results and challenges

We conducted two AB experiments (treatment vs. control) in a massive open online course. The first experiment evaluates deliberate practice activities (DPAs) for developing problem solving expertise as measured by traditional physics problems. We find that a more interactive drag-and-drop format of DPA generates quicker learning than a multiple choice format but DPAs do not improve performance on solving traditional physics problems more than normal homework practice. The second experiment shows that a different video shooting setting can improve the fluency of the instructor which in turn improves the engagement of the students although it has no significant impact on the learning outcomes. These two cases demonstrate the potential of MOOC AB experiments as an open-ended research tool but also reveal limitations. We discuss the three most important challenges: wide student distribution, “open-book” nature of assessments, and large quantity and variety of data. We suggest possible methods to cope with those.

Validating the pre/post-test in a MOOC environment

A standard method for measuring learning is to administer the same assessment before and after instruction. This pre/post-test technique is widely used in education research and has been used in our introductory physics MOOC to measure learning. One potential weakness of this paradigm is that post-test performance gains may result from exposure on the pre-test instead of instruction. This possibility is exacerbated in MOOCs where students receive multiple attempts per item, instant correct/incorrect feedback, and unlimited time (until the due date). To find the size of this problem in our recent MOOCs, we split the student population into two groups, each of which received identical post-tests but different subsets of post-test items on their group pre-test. We report a small overall advantage (2.9% ± 1.7%) on post-test items due to pre-test exposure. However, this advantage is not robust and is strongly diminished when one obviously anomalous item is removed. PACS: 01.40.Fk, 01.40.gf