Mental Representations of Weekdays

Keeping social appointments involves keeping track of what day it is. In practice, mismatches between apparent day and actual day are common. For example, a person might think the current day is Wednesday when in fact it is Thursday. Here we show that such mismatches are highly systematic, and can be traced to specific properties of their mental representations. In Study 1, mismatches between apparent day and actual day occurred more frequently on midweek days (Tuesday, Wednesday, and Thursday) than on other days, and were mainly due to intrusions from immediately neighboring days. In Study 2, reaction times to report the current day were fastest on Monday and Friday, and slowest midweek. In Study 3, participants generated fewer semantic associations for "Tuesday", "Wednesday" and "Thursday" than for other weekday names. Similarly, Google searches found fewer occurrences of midweek days in webpages and books. Analysis of affective norms revealed that participants' associations were strongly negative for Monday, strongly positive for Friday, and graded over the intervening days. Midweek days are confusable because their mental representations are sparse and similar. Mondays and Fridays are less confusable because their mental representations are rich and distinctive, forming two extremes along a continuum of change

The mechanism of DNA unwinding by the eukaryotic replicative helicase

Accurate DNA replication is tightly regulated in eukaryotes to ensure genome stability during cell division and is performed by the multi-protein replisome. At the core an AAA+ hetero-hexameric complex, Mcm2-7, together with GINS and Cdc45 form the active replicative helicase Cdc45/Mcm2-7/GINS (CMG). It is not clear how this replicative ring helicase translocates on, and unwinds, DNA. We measure real-time dynamics of purified recombinant Drosophila melanogaster CMG unwinding DNA with single-molecule magnetic tweezers. Our data demonstrates that CMG exhibits a biased random walk, not the expected unidirectional motion. Through building a kinetic model we find CMG may enter up to three paused states rather than unwinding, and should these be prevented, in vivo fork rates would be recovered in vitro. We propose a mechanism in which CMG couples ATP hydrolysis to unwinding by acting as a lazy Brownian ratchet, thus providing quantitative understanding of the central process in eukaryotic DNA replication

A unified framework for estimating parameters of kinetic biological models

Utilizing kinetic models of biological systems commonly require computational approaches to estimate parameters, posing a variety of challenges due to their highly non-linear and dynamic nature, which is further complicated by the issue of non-identifiability. We propose a novel parameter estimation framework by combining approaches for solving identifiability with a recently introduced filtering technique that can uniquely estimate parameters where conventional methods fail. This framework first conducts a thorough analysis to identify and classify the non-identifiable parameters and provides a guideline for solving them. If no feasible solution can be found, the framework instead initializes the filtering technique with informed prior to yield a unique solution.publishe