Mechanisms of Telomerase Binding to Telomeres

There are essentially two alternative mechanisms for the binding of telomerase to telomeres, assuming that a protective component is initially bound to the telomerase binding region on the telomeres. Either the protective (or blocking) agent first dissociates and telomerase binds thereafter, or telomerase binds first and the protective agent then dissociates from the ternary complex. In the limit, this second possibility permits the ternary complex to become a transition complex (creating another possible mechanism). Numerical simulation of both rapid mixing and chemical relaxation is used to study these alternatives. We aim to determine how the mechanisms may be distinguished experimentally and identify an appropriate experimental design. We show that rapid mixing experiments are better than chemical relaxation experiments, since the latter are more affected by the statistics of single molecule kinetics. However, hidden fast steps can only be revealed by chemical relaxation. The detection of mechanistic changes hinges on linking fluorescence reporters to the reaction components, either directly (chemically) or indirectly (via an indicator reaction). Fluorescence is excited by two-photon absorption in a small reaction volume. Various detection strategies and design issues are examined, including limitations imposed by diffusion. Constant rather than stopped flow is shown to be preferable

Domains of Water Molecules Provide Mechanisms of Potentization in Homeopathy

In homeopathy, high potentization means such high dilution that there is no longer even one molecule of the original active agent per gram of the mixture. Nevertheless such high dilutions apparently remain effective. We develop a possible mechanism for homeopathic potentization to explain this phenomenon. This mechanism consists of three consecutive processes: initiation, multiplication, and amplification. Initiation is the mechano-chemical generation, by strong shaking following each dilution step, of radicals which remain in existence by mutual stabilization in simultaneously formed electronic domains. Multiplication transfers electronic excitation level structures from the original homeopathic agent to these radical-containing domains, stabilizing them further. These stabilized domains participate in the multiplication process until all the domains contain the critical information. Amplification is the generation of the same number of information-containing domains as existed prior to dilution. This amplification step can be repeated any number of times, with the original agent eventually diluted to negligible levels but the information-containing component regenerated to the same concentration in each step. In our first model we assume each domain is contained in a separate water cluster. In an alternative mechanism we consider two domains contained within one water cluster, altering the initiation process. The equations derived from these mechanisms are linked to observables (indicators) and may be used to obtain precise numbers for rate constants and concentrations from future experiments, some of which are outlined

We favor formal models of heuristics rather than lists of loose dichotomies: a reply to Evans and Over

In their comment on Marewski et al. (good judgments do not require complex cognition, 2009) Evans and Over (heuristic thinking and human intelligence: a commentary on Marewski, Gaissmaier and Gigerenzer, 2009) conjectured that heuristics can often lead to biases and are not error free. This is a most surprising critique. The computational models of heuristics we have tested allow for quantitative predictions of how many errors a given heuristic will make, and we and others have measured the amount of error by analysis, computer simulation, and experiment. This is clear progress over simply giving heuristics labels, such as availability, that do not allow for quantitative comparisons of errors. Evans and Over argue that the reason people rely on heuristics is the accuracy-effort trade-off. However, the comparison between heuristics and more effortful strategies, such as multiple regression, has shown that there are many situations in which a heuristic is more accurate with less effort. Finally, we do not see how the fast and frugal heuristics program could benefit from a dual-process framework unless the dual-process framework is made more precise. Instead, the dual-process framework could benefit if its two “black boxes” (Type 1 and Type 2 processes) were substituted by computational models of both heuristics and other processes

Executive function and intelligence in the resolution of temporary syntactic ambiguity: An individual differences investigation

In the current study, we examined the role of intelligence and executive functions in the resolution of temporary syntactic ambiguity using an individual differences approach. Data were collected from 174 adolescents and adults who completed a battery of cognitive tests as well as a sentence comprehension task. The critical items for the comprehension task consisted of object/subject garden paths (e.g. While Anna dressed the baby that was small and cute played in the crib.), and participants answered a comprehension question (e.g. Did Anna dress the baby?) following each one. Previous studies have shown that garden-path misinterpretations tend to persist into final interpretations. Results showed that both intelligence and processing speed interacted with ambiguity. Individuals with higher intelligence and faster processing were more likely to answer the comprehension questions correctly, and specifically, following ambiguous as opposed to unambiguous sentences. Inhibition produced a marginal effect, but the variance in inhibition was largely shared with intelligence. Conclusions focus on the role of individual differences in cognitive ability and their impact on syntactic ambiguity resolution

Forecasting elections from voters’ perceptions of candidates’ ability to handle issues

When deciding for whom to vote, voters should select the candidate they expect to best handle issues, all other things equal. A simple heuristic predicted that the candidate who is rated more favorably on a larger number of issues would win the popular vote. This was correct for nine out of ten U.S. presidential elections from 1972 to 2008. We then used simple linear regression to relate the incumbent’s relative issue ratings to the actual two-party popular vote shares. The resulting model yielded out-of-sample forecasts that were competitive with those from the Iowa Electronic Markets and other established quantitative models. This model has implications for political decision-makers, as it can help to track campaigns and to decide which issues to focus on

Choosing Among Alternative New Product Development Projects: The Role of Heuristics

The initial screening decision that marketing managers make is critical. It requires the selection of which innovation project to invest in, which is fundamental to marketing success. However, our knowledge of how managers make these decisions and how this impacts performance is limited. By drawing upon cognitive psychology and the managerial decision-making literature, we address two critical questions. The first question focuses on identifying specific decisionmaking types (e.g., specific heuristics, intuition) used when making an innovation-screening decision. Based on this analysis and prior research, we develop specific decision-maker profiles about how an individual manager decides. The second research question is about connecting these profiles with performance. Specifically, it addresses what the consequences of different decision-maker profiles are on the perceived accuracy and speed of decision-making? Data were collected from 122 senior managers in these industries. We find that when heuristics are used alone, or concurrently with intuition, managers make decisions that are as accurate as when they rely on analytical decision-making. However, the process is significantly faster. The findings provide an important step towards a more comprehensive understanding of decisionmaking at the front-end of innovation