motifDiverge: a model for assessing the statistical significance of gene regulatory motif divergence between two DNA sequences

Next-generation sequencing technology enables the identification of thousands of gene regulatory sequences in many cell types and organisms. We consider the problem of testing if two such sequences differ in their number of binding site motifs for a given transcription factor (TF) protein. Binding site motifs impart regulatory function by providing TFs the opportunity to bind to genomic elements and thereby affect the expression of nearby genes. Evolutionary changes to such functional DNA are hypothesized to be major contributors to phenotypic diversity within and between species; but despite the importance of TF motifs for gene expression, no method exists to test for motif loss or gain. Assuming that motif counts are Binomially distributed, and allowing for dependencies between motif instances in evolutionarily related sequences, we derive the probability mass function of the difference in motif counts between two nucleotide sequences. We provide a method to numerically estimate this distribution from genomic data and show through simulations that our estimator is accurate. Finally, we introduce the R package {\tt motifDiverge} that implements our methodology and illustrate its application to gene regulatory enhancers identified by a mouse developmental time course experiment. While this study was motivated by analysis of regulatory motifs, our results can be applied to any problem involving two correlated Bernoulli trials

Teaching Science to Students from Rural Mexico: Learning more about ELL Students\u27 Communities of Origin.

George Roberts has been teaching ninth-grade Earth science in Gardston, Iowa, for 10 years. This year, as chair of Gardston High School\u27s science department, he agreed to have all the English Language Learner (ELL) students assigned to his classes. George\u27s goal was to learn more about the needs of these students and arrive at a set of techniques he could share with the rest of his science team. Unlike many other science educators, George has a distinct advantage: The majority of ELLs at Gardston High School immigrate from a particular community

Center for HPV Research at IUPUI

poster abstractHuman Papillomavirus (HPV) infection is highly prevalent among women and men and is associated with a number of diseases including genital warts, cervical cancers, other anogenital cancers in both men and women, and cancers of the head and neck. HPV infections are also associated with millions of dollars in annual health care costs. Two vaccines have been developed to prevent HPV infection. Both are approved for use in females ages 9 through 26, and one vaccine is approved for use in 9 to 26 year old males as well. Both vaccines are efficacious, safe, and cost-effective. Despite the great promise of HPV vaccines, vaccination rates in the U.S. are much lower than desired, with 2011 data indicating that 53% of 13-17 year old females received one or more doses and only 37% completed the 3-dose series. The ongoing medical, psychosocial, and financial costs of HPV infection indicate the need for comprehensive, cross-disciplinary research efforts coordinated with community outreach. We have established the Center for Human Papillomavirus (HPV) Research at IUPUI; which fosters cohesion and collaboration among investigators from multiple disciplines and departments at IUPUI, IU Bloomington, and University of Notre Dame pursuing HPV-related research. This group of accomplished senior faculty and promising junior scholars represents a growing synergy between basic, clinical, and social/behavioral sciences. The Center for HPV Research will provide formal infrastructure and resources for pilot research projects, and a collaborative environment for development of proposals for external funding. By capitalizing on the unique strengths of an internationally recognized faculty and IUPUI’s remarkable culture of collaborative and interdisciplinary research, we will establish a world-class center for HPV research, research training, and research translation. The overall mission of the Center for HPV Research will be to improve understanding of HPV transmission, infection, and prevention of HPV infection and its consequences

Space Shuttle Propulsion System Reliability

This session includes the following sessions: (1) External Tank (ET) System Reliability and Lessons, (2) Space Shuttle Main Engine (SSME), Reliability Validated by a Million Seconds of Testing, (3) Reusable Solid Rocket Motor (RSRM) Reliability via Process Control, and (4) Solid Rocket Booster (SRB) Reliability via Acceptance and Testing

High School Students\u27 Attitudes about Firearms Policies

Purpose: To examine high school students’ attitudes about firearm policies and to compare their attitudes with those of adults. Methods: The Hamilton Youth and Guns Poll is the first national survey of high school students about their attitudes concerning firearm policies. Questions were asked of 1005 sophomores, juniors, and seniors about their actual (i.e., direct) exposure (e.g., presence of a gun in the home) and about their social (i.e., indirect) exposure (e.g., whether the student could get a gun) to firearms and related violence. Population weights were applied, and multivariate logistic regression was used to examine the relationship between demographic and exposure variables and opinions about firearm policies. Results: Most high school students supported more restrictive firearm policies. Opinions varied little by demographic variables with the exception of gender. Females were significantly more supportive of most firearm policies. Actual exposure was a more consistent predictor than social exposure. Students living in a home with a gun, particularly a handgun, were less likely to support most restrictive gun policies. Conclusions: Most high school students in the United States favor stringent policies governing firearms. Adolescents\u27 attitudes about firearm policies parallel those of adults

Noncoding Sequences Near Duplicated Genes Evolve Rapidly

Gene expression divergence and chromosomal rearrangements have been put forward as major contributors to phenotypic differences between closely related species. It has also been established that duplicated genes show enhanced rates of positive selection in their amino acid sequences. If functional divergence is largely due to changes in gene expression, it follows that regulatory sequences in duplicated loci should also evolve rapidly. To investigate this hypothesis, we performed likelihood ratio tests (LRTs) on all noncoding loci within 5 kb of every transcript in the human genome and identified sequences with increased substitution rates in the human lineage since divergence from Old World Monkeys. The fraction of rapidly evolving loci is significantly higher nearby genes that duplicated in the common ancestor of humans and chimps compared with nonduplicated genes. We also conducted a genome-wide scan for nucleotide substitutions predicted to affect transcription factor binding. Rates of binding site divergence are elevated in noncoding sequences of duplicated loci with accelerated substitution rates. Many of the genes associated with these fast-evolving genomic elements belong to functional categories identified in previous studies of positive selection on amino acid sequences. In addition, we find enrichment for accelerated evolution nearby genes involved in establishment and maintenance of pregnancy, processes that differ significantly between humans and monkeys. Our findings support the hypothesis that adaptive evolution of the regulation of duplicated genes has played a significant role in human evolution

In-situ observation of evolving microstructural damage and associated effective electro-mechanical properties of PZT during bipolar electrical fatigue

We investigate the fatigue behavior of bulk polycrystalline lead zirconate titanate (PZT) during bipolar electric field cycling. We characterize the frequency- and cycle-dependent degradation in both the effective electro-mechanical properties (specifically, the electrical hysteresis and the macroscopic viscoelastic stiffness and damping measured by Broadband Electromechanical Spectroscopy, BES) and the microstructural damage evolution (quantified via scanning electron microscopy). The BES setup enables the mechanical characterization while performing electrical cycling so as to measure the evolving viscoelasticity without remounting the sample; particularly measuring the viscoelastic damping allows us to gain insight into the ferroelectric domain wall activity across the full electric hysteresis and over the full range of cycles. A clear dependence on the electric cycling frequency is observed in the rates of degradation of all measured properties including an up to 10% increase in dynamic compliance and a 70% decrease in electric displacement magnitude. We quantify the evolving micro-crack density across wide ranges of numbers of cycles and compare with changes in the effective compliance. Interestingly, the observed strong degradation in the ferroelectric hysteresis is contrasted by relatively mild changes in the effective viscoelastic moduli, while samples clearly indicate increasing levels of micro-damage

“Pifá, Bananas, Oranges Are Our Forests”: Agroforestry and Development among Smallholder Farmers in Panama

Deforestation and forest fragmentation continue unabated in many parts of the world. Scholars point to the expansion of the agricultural frontier as a driver of forest and biodiversity loss. Government agencies and non-governmental organizations (NGOs) often promote agroforestry as a sustainable development strategy for combating deforestation while improving the livelihoods of smallholder farmers. Yet agroforestry projects designed by outsiders who have technical expertise but relatively little local or traditional knowledge can bring negative outcomes for farmers, local communities, and farmer associations. Prescriptive ideas from governments and NGOs may clash with or even contradict local understandings and practices of how forests, fields, and resources should be managed. Though farmers may participate in state and outsider projects, their decisions to embrace, ignore, or negotiate on their own terms how resources are managed ultimately determine the contents and contours of agricultural and forest landscapes. The Panamanian government’s Ministry of Environment, national institutions, and NGOs are promoting agroforestry projects among smallholder farmer association members. I compare the perspectives of farmer association members, non-members, and NGO and government staff to examine how farmers practice agroforestry, the reported benefits of agroforestry, the value of being part of a farmer association, and how agroforestry is supporting (or not) conservation in the Santa Maria River watershed and in the outskirts of Santa Fe National Park in Panama. Results of the research show how micro-level natural resource management of smallholder farmers and livelihood strategies is linked with macro-level projects and discourse about agroforestry. Methods include semi-structured interviews, participatory mapping, and participant observation among smallholder farmers and NGO and government staff as well as the placement of camera traps on farms and in SFNP. The twenty-month ethnographic study reveals how farmers respond to the messages of environmental NGOs, government, and other outside actors. The significance of the project is in increasing knowledge about the complexities of managing natural resources for conservation while improving livelihoods