A simple model of unbounded evolutionary versatility as a largest-scale trend in organismal evolution

The idea that there are any large-scale trends in the evolution of biological organisms is highly controversial. It is commonly believed, for example, that there is a large-scale trend in evolution towards increasing complexity, but empirical and theoretical arguments undermine this belief. Natural selection results in organisms that are well adapted to their local environments, but it is not clear how local adaptation can produce a global trend. In this paper, I present a simple computational model, in which local adaptation to a randomly changing environment results in a global trend towards increasing evolutionary versatility. In this model, for evolutionary versatility to increase without bound, the environment must be highly dynamic. The model also shows that unbounded evolutionary versatility implies an accelerating evolutionary pace. I believe that unbounded increase in evolutionary versatility is a large-scale trend in evolution. I discuss some of the testable predictions about organismal evolution that are suggested by the model

Graduate Recital: Daniel G. Castillon III, Horn; Valen Pao, Piano; April 30, 2023

Kemp Recital HallApril 30, 2023Sunday Evening9:00 p.m

CHOPCHOP: a CRISPR/Cas9 and TALEN web tool for genome editing

Major advances in genome editing have recently been made possible with the development of the TALEN and CRISPR/Cas9 methods. The speed and ease of implementing these technologies has led to an explosion of mutant and transgenic organisms. A rate-limiting step in efficiently applying TALEN and CRISPR/Cas9 methods is the selection and design of targeting constructs. We have developed an online tool, CHOPCHOP (https://chopchop.rc.fas.harvard.edu), to expedite the design process. CHOPCHOP accepts a wide range of inputs (gene identifiers, genomic regions or pasted sequences) and provides an array of advanced options for target selection. It uses efficient sequence alignment algorithms to minimize search times, and rigorously predicts off-target binding of single-guide RNAs (sgRNAs) and TALENs. Each query produces an interactive visualization of the gene with candidate target sites displayed at their genomic positions and color-coded according to quality scores. In addition, for each possible target site, restriction sites and primer candidates are visualized, facilitating a streamlined pipeline of mutant generation and validation. The ease-of-use and speed of CHOPCHOP make it a valuable tool for genome engineering

A Fully Bayesian Approach for Combining Multilevel Failure Information in Fault Tree Quantification and Corresponding Optimal Resource Allocation

This paper presents a fully Bayesian approach that simultaneously combines basic event and statistically independent higher event-level failure data in fault tree quantification. Such higher-level data could correspond to train, sub-system or system failure events. The full Bayesian approach also allows the highest-level data that are usually available for existing facilities to be automatically propagated to lower levels. A simple example illustrates the proposed approach. The optimal allocation of resources for collecting additional data from a choice of different level events is also presented. The optimization is achieved using a genetic algorithm

Graduate Joint Recital: Daniel G. Castillon III, Horn; Zhiyuan Gao, Horn; Grace Eom, Piano; Valen Pao, Piano; October 31, 2022

Kemp Recital HallOctober 31, 2022Monday Evening6:30 p.m

CHOPCHOP v3: expanding the CRISPR web toolbox beyond genome editing

The CRISPR–Cas system is a powerful genome editing tool that functions in a diverse array of organisms and cell types. The technology was initially developed to induce targeted mutations in DNA, but CRISPR–Cas has now been adapted to target nucleic acids for a range of purposes. CHOPCHOP is a web tool for identifying CRISPR–Cas single guide RNA (sgRNA) targets. In this major update of CHOPCHOP, we expand our toolbox beyond knockouts. We introduce functionality for targeting RNA with Cas13, which includes support for alternative transcript isoforms and RNA accessibility predictions. We incorporate new DNA targeting modes, including CRISPR activation/repression, targeted enrichment of loci for long-read sequencing, and prediction of Cas9 repair outcomes. Finally, we expand our results page visualization to reveal alternative isoforms and downstream ATG sites, which will aid users in avoiding the expression of truncated proteins. The CHOPCHOP web tool now supports over 200 genomes and we have released a command-line script for running larger jobs and handling unsupported genomes. CHOPCHOP v3 can be found at https://chopchop.cbu.uib.nopublishedVersio

Senior Recital: Nathaniel J. Parson, Horn; Daniel G. Castillon III, Horn; Grace Eom, Piano; Valen Pao, Piano; November 13, 2022

Kemp Recital HallNovember 13, 2022Sunday Evening5:30 p.m

Short-term duodenal seal oil administration normalised n-6 to n-3 fatty acid ratio in rectal mucosa and ameliorated bodily pain in patients with inflammatory bowel disease

BACKGROUND: A high dietary intake of n-6 compared to n-3 fatty acids (FAs) may promote the production of pro-inflammatory eicosanoids and cytokines. In two recent studies, short-term (10-day) duodenal administration of n-3 polyunsaturated fatty acid rich seal oil ameliorated joint pain in patients with inflammatory bowel disease (IBD). Using unpublished data from these two studies we here investigated whether normalisation of the n-6 to n-3 FA ratio in blood and tissues by seal oil administration was associated with improved health related quality of life (HRQOL) as assessed by the generic short-form 36 (SF-36) questionnaire. RESULTS: In the first pilot study, baseline n-6 to n-3 FA ratio in rectal mucosal biopsies from 10 patients with IBD (9 of those had joint pain) was significantly increased compared with that in 10 control patients without IBD or joint pain. Following seal oil administration, the n-6 to n-3 FA ratio of the IBD-patients was significantly lowered to the level seen in untreated controls. In the subsequent, randomized controlled study (n = 19), seal oil administration reduced the n-6 to n-3 FA ratio in blood similarly and also the SF-36 assessed bodily pain, while n-6 FA rich soy oil administration had no such effect. CONCLUSION: In these two separate studies, short-term duodenal administration of seal oil normalised the n-6 to n-3 FA ratio in rectal mucosa and improved the bodily pain dimension of HRQOL of patients with IBD-related joint pain. The possibility of a causal relationship between n-6 to n-3 FA ratio in rectal mucosa and bodily pain in IBD-patients warrants further investigations

The diplomat's dilemma: Maximal power for minimal effort in social networks

Closeness is a global measure of centrality in networks, and a proxy for how influential actors are in social networks. In most network models, and many empirical networks, closeness is strongly correlated with degree. However, in social networks there is a cost of maintaining social ties. This leads to a situation (that can occur in the professional social networks of executives, lobbyists, diplomats and so on) where agents have the conflicting objectives of aiming for centrality while simultaneously keeping the degree low. We investigate this situation in an adaptive network-evolution model where agents optimize their positions in the network following individual strategies, and using only local information. The strategies are also optimized, based on the success of the agent and its neighbors. We measure and describe the time evolution of the network and the agents' strategies.Comment: Submitted to Adaptive Networks: Theory, Models and Applications, to be published from Springe