Worcester, MA, United States

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Drake A.G.,College of the Holy Cross, Worcester
Evolution and Development | Year: 2011

Heterochrony is an evolutionary mechanism that generates diversity via perturbations of the rate or timing of development that requires very little genetic innovation. As such, heterochrony is thought to be a common evolutionary mechanism in the generation of diversity. Previous research has suggested that dogs evolved via heterochrony and are paedomorphic wolves. This study uses three-dimensional landmark-based coordinate data to investigate heterochronic patterns within the skull morphology of the domestic dog. A total of 677 adult dogs representing 106 different breeds were measured and compared with an ontogenetic series of 401 wolves. Geometric morphometric analysis reveals that the cranial shape of none of the modern breeds of dogs resembles the cranial shapes of adult or juvenile wolves. In addition, investigations of regional heterochrony in the face and neurocranium also reject the hypothesis of heterochrony. Throughout wolf cranial development the position of the face and the neurocranium remain in the same plane. Dogs, however, have a de novo cranial flexion in which the palate is tilted dorsally in brachycephalic and mesaticephalic breeds or tilted ventrally in dolichocephalic and down-face breeds. Dogs have evolved very rapidly into an incredibly morphologically diverse species with very little genetic variation. However, the genetic alterations to dog cranial development that have produced this vast range of phylogenetically novel skull shapes do not coincide with the expectations of the heterochronic model. Dogs are not paedomorphic wolves. © 2011 Wiley Periodicals, Inc.


Francis A.,College of the Holy Cross, Worcester
Sociology of Health and Illness | Year: 2012

This study examines the stigma experiences of middle-class parents whose children have physical, psychological and behavioural problems. Qualitative interviews with 34 mothers and 21 fathers demonstrate that parents experience two types of stigma: courtesy stigma and the stigma of being a bad parent. While the former stems from close social proximity to stigmatised children, the latter stems from ostensible culpability for children's problems. Both characteristics are social constructs embedded in the larger contexts of an anxious, intensive parenting culture and the problematisation and medicalisation of childhood. As a consequence, mothers, parents whose children have invisible disabilities, and the parents of young children are particularly susceptible to negative labelling. These findings highlight the constructed and political nature of parents' stigmatisation. © 2012 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.


Grant
Agency: NSF | Branch: Continuing grant | Program: | Phase: Molecular Biophysics | Award Amount: 567.12K | Year: 2013

Intellectual Merit
This project will study the chemical mechanism of protein splicing. Protein splicing is the means by which an intervening polypeptide, or intein, catalyzes its own removal from flanking polypeptides, or exteins. The intein also links the extein segments. The research project will investigate the following: 1. How the activity of an intein from an extreme thermophile is influenced by its unusual structural stability. The investigative approaches will examine how the intein balances the need to be stable at high temperatures with the need to be sufficiently flexible to be catalytically active; 2. The manner in which conserved residues in the intein catalyze each step of the reaction, providing insight into how enzymes catalyze and coordinate multi-step reactions at a single active site without cofactors; 3. The catalysis of cyclization of the amino acids asparagine or glutamine, coupled to peptide bond cleavage. This is an unusual reaction in protein chemistry which will be studied in the context of an intein as well as with a combination of model peptide experiments and computational modeling; 4. The regulation of intein activity, either by temperature or oxidation state. This process of regulation might suggest how inteins could control the activity of their flanking, interrupted proteins; 5. The autoprocessing of hedgehog-like domains, which resemble inteins in structure and sequence, including how conserved residues and the binding of cholesterol may influence the initial step of the reaction. These aspects of protein splicing will be investigated with the use of a combination of structural, biophysical, biochemical and computational techniques in projects suitable for undergraduates.

Broader Impact
The research program will have a significant impact on the careers of undergraduate research students. The undergraduates will perform the experiments, present the results at national meetings and in peer-reviewed publications, and, through close mentoring, prepare to be future leaders in STEM. Students from the Biochemistry Concentration at the College of Holy Cross will be recruited to work on this project. In addition to research activities, the students will sponsor outreach in the community by hosting lectures aimed at broad audiences and by participating in the Science Ambassadors student outreach program. The project will broaden access to STEM by recruiting local students to the lab through the Worcester Pipeline which is a program that is conducted in conjunction with the University of Massachusetts Medical School


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: Molecular Biophysics | Award Amount: 748.27K | Year: 2015

The goal of the research program is to study the chemistry of proteins from thermophilic organisms. Thermophiles are microorganisms that live in places that are very hot and are often under very high pressure, such as deep-sea thermal vents. The program will investigate how these proteins can function at such extreme conditions, which could unfold or prevent the activity of proteins from organisms that grow under more hospitable conditions. This would allow insight into strategies that proteins use to stabilize their structure while remaining chemically active. In particular, the program will examine a class of enzymes (protein catalysts that facilitate chemical reactions) called inteins. Inteins interrupt other proteins, and must promote their own removal so that the interrupted proteins can function. Learning how this reaction is regulated may suggest roles for the splicing reaction and potentially new ways in which gene expression can be controlled. Inteins, and thermophilic enzymes more broadly, both have useful biotechnology applications, and a deeper understanding of structure and function will improve these tools. The broader impact of the program includes the development of the next generation of scientists and leaders in STEM, through direct training of undergraduate research students, through outreach to the youngest scientists in the Worcester community, and through increasing access to scientific research for under-represented groups both in the Worcester student community and with Holy Cross first year students.

The research program seeks to understand the mechanism of protein splicing, a post-translational modification catalyzed by an intein. It will study unresolved questions about the catalytic mechanism at atomic-level resolution using both X-ray crystallography and NMR structure and dynamics experiments coupled with biochemical techniques. It will use a biophysical model peptide system, integrated with computational techniques, to investigate side chain cyclization coupled to peptide bond cleavage. It will examine how the structure of thermophilic inteins influences their activity and conformational flexibility, and investigate the physiological role of splicing. In addition, the program will have significant impact on our understanding of how enzymes catalyze multi-step reactions at a single active site and how thermophilic enzymes balance activity and stability through protein dynamics.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: MACROSYSTEM BIOLOGY | Award Amount: 278.58K | Year: 2014

The transfers of carbon, nutrients and pollutants from the land to streams and their changes as they move through river networks are issues that motivate environmental scientists and water resource managers. Dissolved organic matter (DOM) is a central chemical in streams and rivers that affects the forms and movements of contaminants, light penetration through the water, metabolism of life in the streams, pH, and the efficiency of water treatments by municipalities. This study aims to improve predictions of DOM formation and movement from small headwater streams and our understanding of the factors that change the amount and forms of DOM during as it moves downstream. One goal of this research is to greatly improve a computer model of DOM transport and transformation as it moves through a watershed and into the headwater streams. This model links rainfall and runoff that generate streamflow to the biological and chemical processes that lead to changes in the amount and forms of DOM. The model will be tested against actual measurements of DOM made in several headwater streams of the Connecticut River along its length. Measurements will then also be made in larger parts of the Connecticut River downriver that will help explain how DOM changes along the entire drainage network. This project challenges a long standing picture of how streams and rivers work, called the River Continuum Concept, proposing that a newer view may be required, referred to as the Pulse-Shunt Concept.

This project will involve graduate students and a post-doctoral associate in the laboratory, field, and modeling ends of the research. It will also build on a partnership with the Connecticut Science Museum to construct educational activities and displays related to watershed ecology and management for the general public.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: STATISTICS | Award Amount: 135.49K | Year: 2014

This project will develop an efficient change point algorithm that not only will indicate when change points occur, but also provide uncertainty estimates as to the number and exact timing of these changes. Applications of this model are widespread and include any field where long sequences of data are collected such as medicine (e.g. EEG readings), economics (e.g. stock market data, coal mining disasters), and climate (e.g. temperature readings, glacial records). More specifically, a 5 million year record of global ice volume shows at least two distinct changes. The first, around 2.7 million years ago, represents an increase in the amount of ice volume on the Earth as permanent glaciers began to form in the northern hemisphere, whereas a more recent change around 0.8 million years ago represents a gradual change in the frequency of major glacial melting events from every 40,000 to every 100,000 years. A more prominent example concerns NCDCs global temperature anomalies data set that many have cited as evidence of global warming. This record indicates three changes in the rate of temperature increases on the Earth over the last 133 years - in 1906, 1945, and either 1963 or 1976. The algorithm will be able to handle sequential data, giving it the ability to quickly update itself as each new observation is recorded, and will be able to accurately predict where in the data set a change point has occurred.

It is well known that long time series are often heterogeneous in nature, any attempt to model these data sets may have to account for parameters that change through time. The difference can be as simple as a change in the mean, slope, or frequency of the underlying signal. However, the identification of ?change points? is not always a trivial task as the number of potential solutions grows exponentially with the length of the data set, rendering brute force attempts to solve the problem infeasible. Previous work on a Bayesian change point algorithm has produced an efficient and exact probabilistic solution to the multiple change point problem by using dynamic programming-like recursions to reduce the computational complexity from exponential to quadratic. Samples drawn from the joint posterior distribution of the change point locations quantify the uncertainty in both the number and timing of changes in the data set. In this project, the existing change point model will be modified to handle sequential data. Once this initial objective is complete, research will turn towards further modifications that include the ability to handle correlated error terms and an approximate algorithm that has linear complexity, bringing the computational complexity down to a point where a time series of any length can be analyzed. The project fits naturally with undergraduate education and will serve as the basis of summer research projects, senior theses, and a potential seminar course for a new statistics program. The software developed through this project will be made publicly available so as to make this cutting-edge statistical methodology accessible to researchers in a wide variety of fields.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: SOCIAL PSYCHOLOGY | Award Amount: 181.83K | Year: 2014

Stigmatized individuals experience some of the most formidable health disparities in American society, and prevailing views suggest that these disparities are attributable in part to discrimination. However, growing evidence suggests that individuals living with stigmas that are largely concealable - and who are largely shielded from direct discrimination - also experience similar disparities. The current project examines the possibility that the stress of interpersonal disclosure, a recurrent and unique stressor among people living with concealable stigmatized identities (i.e., socially devalued attributes that cannot readily be seen) may be a primary pathway by which concealable stigmas affect psychological and physical health. Specifically, this research tests whether interpersonal disclosure is stressful and whether individuals chronic fears of stigmatization and the surrounding communitys prejudice exacerbate these stress effects and downstream psychological and physical health.

The proposed research will significantly advance the study of individuals living with concealable stigmatized identities, which, as a whole, constitute an understudied population of Americans. This knowledge has the potential to inform intervention and programmatic efforts designed to help individuals living with concealable stigmatized identities to buffer themselves against the effects of social devaluation; policy makers and community stakeholders in their efforts to reduce prejudice; and public health practitioners in their goals to reduce health disparities. As such, the proposed research has the potential to aid in reaching the NSF and U.S. Department of Health and Human Services goal of identifying and ameliorating the psychosocial factors that contribute to health disparities. Research activities outlined in this proposal will also substantially transform the training environment for many of the countrys future medical providers and social scientists by providing experiential research and learning opportunities that demonstrates the complex biopsychosocial processes that could affect downstream health disparities.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: | Award Amount: 137.23K | Year: 2012

The goal of this project is to further develop the study of central configurations, an important and active sub-field of celestial mechanics. A central configuration is a special set of positions where the force on each body due to gravity points in the opposite direction of that bodys position vector (with respect to the center of mass). Finding a central configuration involves solving a complicated system of nonlinear algebraic equations. Central configurations are important since they lead to families of homographic and homothetic solutions in both the N-body and N-vortex problems. Specific aims of the project include classifying five-body co-circular central configurations, studying relative equilibria in the four and five-vortex problems, using symmetry to simplify the study of central configurations for special choices of the masses, analyzing the linear stability of the corresponding relative equilibria, and describing certain symmetric families of solutions. These topics will be explored using a combination of analysis and modern and computational algebraic geometry.

The N-body problem concerns the motion of celestial bodies (stars, planets, asteroids, even spaceships) interacting under their mutual gravitational attraction. Although inherently a mathematical discipline, applications to astronomy and spacecraft transport are plentiful. For example, the recent astronomical discovery of an asteroid at a ``Trojan point in the Earth-Sun system came centuries after the mathematical work of Lagrange on three-body central configurations. The N-vortex problem is a widely used model for understanding vorticity evolution in fluid dynamics. Some of the most important types of solutions in these problems are periodic in nature, returning to their initial configuration after some fixed amount of time. Among this class of solutions are simple, rigidly rotating orbits, known as relative equilibria, where the size and shape of the configuration is unchanged throughout the motion. Locating a relative equilibrium requires first finding a central configuration. Analyzing the structure and stability of relative equilibria leads to a greater understanding of the complexities in the full problem. In celestial mechanics this study is useful for plotting spacecraft trajectories and for discovering inexpensive methods of exploring space. In addition, locating stable solutions provides key information about the orbits astronomers and other researchers expect to see in the universe. An important priority of the project is to mentor, support and collaborate with undergraduate researchers interested in the field.


Grant
Agency: NSF | Branch: Continuing grant | Program: | Phase: Genetic Mechanisms | Award Amount: 134.51K | Year: 2017

All species share many genes in common with other organisms, but each species has a handful of new genes that came into existence only recently and are thus either unique to that species or shared only with its closest relatives. In a variety of animal and plant species, many such newly evolved genes are thought to impact the male reproductive system. The goal of this project is to determine how newly evolved genes influence male reproductive success by focusing on those that affect sperm function in the fruit fly model system, Drosophila melanogaster. This research will generate important basic science knowledge about how new genes change reproductive systems to the benefit of their carriers. Its broader implications relate to the potential development of strategies that inhibit the reproduction of insect species that are agricultural pests or that transmit human diseases, such as the mosquitoes that carry malaria and the Zika virus. By establishing the importance of lineage-specific genes for male reproduction, this research may aid in the development of smart pesticides, or genetic manipulation strategies that target genes found only in the problematic insect species and not other beneficial insects in the surrounding environment. This project will also benefit society by increasing the participation of undergraduates in original research and supporting innovative mentoring programs that encourage the persistence of students from groups that are underrepresented in STEM disciplines. The research will be conducted at an exclusively undergraduate institution and will be carried out, in part, by students in an intermediate-level Genetics course and students conducting independent research in a faculty members lab. The project will also support a program in which first-year college students from underrepresented groups join research labs immediately upon their arrival on campus, providing these students with a sense of community and introducing them to scientific research as they begin college. Finally, the project will support a student-run organization that pairs college students with girls from underserved public high schools for weekly mentoring sessions that include assistance with math and science skills.

This project focuses specifically on so-called de novo genes that have recently evolved from non-coding DNA sequence. Previous research from a variety of taxa has focused on identifying these genes and studying their emergence within populations, but little is known about their specific molecular and cellular functions. Working in the safe and genetically tractable Drosophila melanogaster model system, this project will begin by using RNA interference to screen all de novo genes expressed in the testes for effects on male fertility. Genes whose expression is required for full fertility will become targets for functional characterization, which will be facilitated by the development of tagged transgenes, antibodies, and CRISPR/Cas9-mediated knockout mutant lines. These tools will be used in cytological experiments to investigate how each gene influences the process of spermatogenesis and/or the function of mature sperm after they are transferred to females. In parallel with these functional genetic analyses, the evolutionary history of each gene will be examined across related Drosophila species in order to understand how the gene arose from non-coding DNA sequence and how the protein it encodes has evolved since its emergence. For de novo genes that show signatures of rapid divergence between species, further genetic experiments will be conducted to determine the functional consequences of divergence. Taken together, these experiments will provide a comprehensive view of how the process of new gene creation can modify reproductive phenotypes.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: | Award Amount: 43.94K | Year: 2013

SES-1324000
PI: Andrew Fullerton
Oklahoma State University

SES-1324019
PI: Jeffrey Dixon
Holy Cross College

Part-time work is an important potential source of insecurity that workers around the world face, but it is understudied in the context of worker insecurity, partly because of the cross-national variation in the meanings and measurements of part-time work. This project examines the relationship between part-time work and several forms of perceived worker insecurity, including the perceived threat of job loss in the near future, worries about the threat of job loss, and the perceived difficulty of finding a comparable job in the labor market. Focusing on multiple levels of analysis, this project asks: Do part-time workers feel more insecure than full-time workers? Does this vary by country? At the country level, what is the relationship between the size of the part-time workforce and average levels of insecurity? Based on individual-level data from the 2005 International Social Survey Program (ISSP) Work Orientations III module linked to macro-level data, preliminary results reveal that workers in part-time jobs feel more insecure than workers in full-time jobs, all else equal. However, the size of the part-time gap in worker insecurity varies substantially across countries, and countries with higher rates of part-time work tend to have lower levels of average worker insecurity. To account for these seemingly contradictory findings, the investigators develop a model of the institutionalization of part-time work, which refers to the creation and perpetuation of scripts and shared rules that guide decisions and actions regarding employers use of part-time work. Using this framework, the research hypothesizes that the gap in perceived worker insecurity between part-time and full-time workers will be smallest in countries in which part-time work has been institutionalized to such a degree that: A) a substantial number of men work part-time (even if most part-time workers are women), B) part-time workers have the same legal protections and benefits as full-time workers, C) most part-time workers are employed in those positions voluntarily, and D) part-time work is not concentrated in low-wage occupations. This model will be tested with ISSP and other survey data linked to macro-level data, including a country-level dataset that will contain aggregate measures of part-time work and other labor market characteristics for more than 50 countries and several time points between 2000 and 2010.

Broader Impacts
The knowledge gained from this study about the sources of perceived worker insecurity has important implications for scholars and policy makers concerned with the consequences of part-time and other forms of non-standard work on workers health, families, and communities. The results will also bear on debates about flexicurity policies in parts of Europe, which are intended to reconcile employer preferences for flexible work arrangements (such as part-time work) with employment security for workers. Furthermore, the new country-level dataset will be made available to interested scholars, teachers, and researchers to examine part-time work and other types of non-standard work. These data can also be supplemented with other macro- or micro-level data to examine other socioeconomic outcomes. Additionally, this project will involve undergraduate and graduate students who have an interest in quantitative methods of research, comparative sociology, and work and occupations, and the researchers will seek assistants who will help in each stage of this project and gain valuable research skills as a result. Finally, the principal investigators will produce several presentations and scholarly publications based on this project.

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Loading College of the Holy Cross, Worcester collaborators