23rd Hayes Graduate Research Forum (April, 2009)

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The Arts
1st place: Cameron, Kathleen A.
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2nd place: Rainsberg, Bethany
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3rd place: Tashfeen, Asheer
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Biological Sciences
1st place: Li, Jing
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2nd place: Werbeck, Jillian
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3rd place: Voss, Oliver H.
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Business
1st place: Clottey, Toyin
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2nd place: Chen, Jia
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3rd place: Singh, Suresh
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Education and Human Ecology
1st place: Fletcher, Edward Jr.
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2nd place: Lynch, Jamie
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3rd place: Yough, Michael
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Engineering
1st place: Huang, Jiwei
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2nd place: Balasubramanian, Priya
3rd place: Qin, Ruogu
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Food, Agricultural, and Environmental Sciences
1st place: Prabhakar, Veena
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2nd place: Mills, Julianne H.
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3rd place: Bernal, Blanca

Humanities
1st place: Bennett, James
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2nd place: Judkins, Ryan
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3rd place: Whitworth, Lauran

Math and Physical Sciences
1st place: Denney, Kelly D.
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2nd place: Jones, Christopher
3rd place: Watson, Linda
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Poster
1st place: Vedachalam, Sridhar
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2nd place: Shimko, John
3rd place: Rao, Shreyas
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Professional Biological Sciences
1st place: Martin, Chelsea
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2nd place: Kithcart, Aaron
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3rd place: Lathrop, Rebecca
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Social and Behavioral Sciences
1st place: White, Corey
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2nd place: Carlson, Daniel
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3rd place: Adler, Abby
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Regulation of cell fate by caspase-3 and PKCδ and Hsp 27
(2009-04) Voss, Oliver H.; Doseff, Andrea I.
Regulation of cell fate by caspase-3 and Protein Kinase Cδ and heat shock protein 27 Objectives of the study. Apoptosis is an evolutionarily conserved mechanism essential for normal development and defense against viral infections and cancer. Cancer initiation and progression has been associated with a dysregulation of the homeostatic balance between cell proliferation and apoptosis. A key regulator of apoptosis is the cysteine protease, caspase-3. The inability to activate caspase-3 has been associated with resistance to chemotherapy and the progression of leukemia. However, the mechanisms of caspase-3 activation are still largely unknown. Thus, the purpose of this study was to determine how the direct regulators of caspase-3, Protein Kinase Cδ (PKCδ) and heat shock protein 27 (hsp27), mediate apoptosis. Methodology. Primary human monocytes, macrophages and transiently transfected monocytic-like-leukemia cells (THP-1) were used in immunoprecipitations (IP), immunofluorescence (IF), and short inferences RNA to determine the mechanisms involved in apoptosis. Apoptosis and differentiation was determined using DEVD-AFC caspase-3 activity assays and cell flow cytometry analysis respectively. Human purified recombinant proteins were used in caspase-activity assays and in vitro kinase assays to identify the molecular mechanism that regulate caspase-3. Results & Conclusions. We previously found that caspase-3 associates with PKCδ and hsp27. We showed that PKCδ phosphorylates caspase-3 and hsp27 and that PKCδ-dependent phosphorylation of caspase-3 promotes caspase-3 activity. We investigated the role of hsp27 and PKCδ on caspase-3 activation. We found using IF and subcellular fractionation that caspase-3, PKCδ and hsp27 are differentially localized during monocyte apoptosis and monocytes/macrophage differentiation. . We showed in monocytes that, unlike other classical heat shock proteins, the expression of hsp27 was constitutive and unaltered and increased dramatically during monocyte/macrophage differentiation. To determine the role of hsp27 in apoptosis, monocytes overexpressing hsp27 were induced to undergo cell death. We found a significant decrease in apoptosis in cells overexpressing hsp27. Consistently, silencing of hsp27 showed an increase in apoptotic cells upon treatment with chemotherapeutic drugs. We next investigated the mechanisms by which PKCδ and hsp27 regulate caspase-3. We mapped the domains of the association of caspase-3 with its two direct regulators hsp27 and PKCδ. Using IP, we showed that the carboxy-terminal domain of hsp27 associates with the amino-terminal domain of caspase-3 and found that binding of hsp27 inhibited the autocatalytic cleavage required for caspase-3 activation. Together our findings support that caspase-3 activation is regulated by anti- and pro-apoptotic factors. Our results suggest that the caspase-3:hsp27:PKCδ complex localizes in the cytoplasm. Upon activation of cell death, hsp27 and PKCδ relocalized to the nucleus freeing caspase-3 allowing its full activation. High levels of hsp27 inhibit apoptosis and may play a role in monocyte/macrophage differentiation. Significance. In an attempt to induce cell death in cancer cells, we identified a mechanism responsible for the regulation of caspase-3. Our studies demonstrated that hsp27 is a negative regulator of apoptosis and may contribute to the resistant of cancer cells to chemotherapeutic drugs. These findings contributed to the basic understanding of apoptosis and identified potential therapeutic targets for cancer treatment.
Effect of zoledronic acid therapy in an in vivo model of bone invasive feline oral squamous cell carcinoma
(2009-04) Martin, Chelsea; Rosol, Thomas
Objective: To test the hypothesis that zoledronic acid will inhibit tumor-induced osteolysis and reduce tumor growth and invasion in a xenograft mouse model of bone invasive oral squamous cell carcinoma (OSCC). In humans, OSCC is the 6th most common cancer in the world. Bone invasion frequently occurs and is associated with poor prognosis and reduced survival. OSCC is the most commonly diagnosed malignancy of the oral cavity in cats and has a grave prognosis with an average duration of survival of only 2 months. Feline OSCC (FOSCC) is very aggressive and commonly invades bone, which is characterized by osteoclastic bone resorption. Zoledronic acid (ZOL) is a potent third generation nitrogen-containing bisphosphonate which inhibits osteoclastic bone resorption. There are currently no available treatment modalities which significantly improve prognosis or prolong survival of cats with FOSCC. Methods: A luciferase-expressing FOSCC cell line (SCCF2Luc) was injected into the perimaxillary subgingival lamina propria of 30 athymic nude mice. Mice were treated with 100 µg/kg ZOL, or vehicle, twice weekly for 4 weeks. Thirty non-tumor-bearing mice served as controls. Tumor growth was monitored with in vivo bioluminescent imaging and tumor dimensions were determined with calipers. The degree of bone loss was evaluated using faxitron radiography and micro-computed tomography (microCT). A 2mm thick region of interest (ROI) in the rostral skull, incorporating the xenograft and adjacent pre-maxillary and maxillary bone, was selected using µCT and image analysis software. ROI-bone surface area and bone volume were calculated and compared between treatment groups. Tumor invasiveness was evaluated microscopically. Osteolysis and osteoclast activation were evaluated with TRAP histochemistry and histomorphometry. Results and conclusions: Progressive xenograft growth occurred in all mice, as indicated by increasing bioluminescence. Bioluminescence was positively correlated with tumor volume. ZOL treatment significantly reduced tumor growth (in vivo bioluminescence), prevented loss of bone volume and surface area (microCT), and was associated with reduced osteolysis and increased periosteal new bone formation (microCT, faxitron radiography and histomorphometry). ZOL had no effect on tumor invasion around the incisor or into the nasal cavity. ZOL-mediated inhibition of tumor-induced osteolysis was characterized by significantly reduced numbers of TRAP-positive osteoclasts at the tumor-bone interface and was associated with osteoclast vacuolar degeneration. The ratio of eroded to total bone surface was not significantly affected by treatment; indicating that ZOL-mediated inhibition of osteolysis was independent of osteoclast activation and maturation. Significance: This preclinical model of OSCC recapitulates the bone invasive phenotype characteristic of the disease in both humans and cats, and will be useful to future preclinical studies of bone invasive OSCC regardless of species. ZOL reduced FOSCC-induced osteolysis and bioluminescence, but invasive behavior was unchanged. The results of this experiment suggest that ZOL monotherapy would be of limited clinical use in the management of FOSCC, but may be valuable as adjunct therapy with the purpose of maintaining mandibular and maxillary bone volume and function.
The Presentation of Spatial Design using Autonomous Behavior in Virtual Environments
(2009-04) Tashfeen, Asheer; Haase, Jeff
This research is an exploration of virtual environments as it relates to presenting spatial design, specifically focusing on the use of autonomous behavior in virtual characters for simulation purposes. The characters in motion gives the viewer of this environment an understanding of circulation routes, traffic density and space usage (function) among other aspects. Since the characters can "think" by themselves through the programmed artificial intelligence, the resulting simulation may be unexpected. Flaws or miscalculations in the design can be highlighted due to the chaos that arises from the virtual crowd. To conduct the research, two virtual environments were produced and examined. These were modified through an iterative process based on analysis and review by groups of peers, academics, as well as designers in the field. My documentation includes the necessary steps taken prior to production, an analysis of the environments, as well as possible future directions. The existing uses of this technology were also analyzed and compared. Similar to the impact on the design field by the introduction of perspective drawings, the use of virtual environments has the potential of creating a new method of designing, one where design is conceived and experimented on a computer, as opposed to orthographic drawings and perspective vignettes. This is due to the ability of real-time spatial manipulation which allows one to see the direct effect of any proposed change upon the characters in the simulation. One could experience the environment through these autonomous beings, giving us a dimension of sight we could never see otherwise. The functionality of designed space could now be "discovered" by the virtual characters, thus enabling the most ambiguous forms to take on roles we may not have conceived ourselves.
English language learners and distinctions between student-teacher relationships and school climate
(2009-04) Yough, Mike; Woolfolk Hoy, Anita
Belongingness is a fundamental human need (Baumeister & Leary, 1995) and students' sense of belonging in school can be a powerful determinant of how well they do in school (Meyer & Turner, 2006). Thus, a strong sense of belonging may be especially important for disadvantaged students (Solomon, Battistich, Kim, &Watson, 1997) or those going through periods of transitions (Wigfield, Lutz, & Wagner, 2005)-both of which characterize many English language learners (ELL) (Larsen, 2004). Two factors believed to contribute to a sense of school belonging are perceptions of school climate and student-teacher relationships. Perception of positive school climate, or atmosphere, is associated with students who attend school, adopt task goals, and are academically engaged, while positive student-teacher relationships are associated with student engagement, participation, student perceptions of motivating instruction, increased academic performance, teacher ratings of increased self-directed behavior, school liking, school- and class-related interest, and higher levels of life satisfaction (Juvonen, 1996). To date, no studies have directly examined the relation between ELLs' sense of school belonging and English language ability. The intent of this study is to better understand the relationships between English proficiency, level of school involvement, and students' sense of school belonging. Methods The data used in this study was came from the Educational Longitudinal Study of 2002 (ELS:2002) public use data file which included 15,430 10th-grade students enrolled in one of the 752 schools (Ingels, Pratt, Wilson, Burns, Currivan, Roger, & Hubbard-Benasz, 2007). The ELS:2002 surveyed 10th-grade students and their parents, as well as the teachers, principals, and librarians at their schools. The intent of the student questionnaire was to obtain information on students' background, school experiences and activities, plans and goals for the future, employment and out-of-school experiences, language background, and psychological orientation toward learning and was administered in a group setting at school. Results and Discussion A series of four hierarchical multiple regression analyses were conducted. Gender, race, and SES were entered as the first step of each model. The second step consisted of the inclusion of variables associated with participation in school activities. The third step consisted of either self-reported English ability (for ELLs only) or whether participants were native speakers of English (for the full sample). The results indicated that Speaking English as a native language was a significant predictor of positive perceptions of school climate. However, the opposite was true in terms of positive perceptions of student-teacher relationships-being a non-native speaker of English predicted positive student-teacher relations. Implications ELLs are over-represented among the economically disadvantaged (Larsen, 2004) and many are going through periods of transition (Yeh & Inose, 2003). Thus, these students may greatly benefit from a strong sense of school belonging. Yet, the results of this study indicate that ELLs' English proficiency is an important predictor of their perceptions of positive school climate. It is imperative that researchers and educators have a better understanding of factors that contribute to a sense of school belonging for these students. This study is a step toward that direction.
Locomotor Training: The Effects of Treadmill Speed and Body Weight Support on Gait Kinematics
(2009-04) Lathrop, Rebecca; Siston, Robert
Body Weight Supported Treadmill Training (BWSTT) is a rehabilitation method which can help individuals with incomplete Spinal Cord Injuries (SCIs) regain the ability to walk. In BWSTT, a harness is used to support part of the patient's body weight above a treadmill while therapists assist the patient in performing stepping motions. Following SCI, recovery of function is achieved by reorganization of neural pathways in the spinal cord, which is dependent on task-specific rehabilitation. BWSTT is a task-specific program which focuses on replicating the forces and motions experienced during normal walking to help patients achieve recovery of walking ability. While BWSTT has shown positive results, there is no quantitative evidence for which training conditions, specifically treadmill speed and amount of body weight support, most effectively target the muscles to restore normal gait. This study will determine how varying treadmill speed and percentage of body weight support affects the kinematic gait parameters of normal walking. We collected motion capture data from 4 healthy subjects (3 male, 1 female), as they walked on an instrumented treadmill with varied body weight support (0,30,50, and 70% of weight supported) and treadmill speed (self-selected speed (SS), 0.5xSS, and 1.5xSS). We analyzed the motion capture data and developed dynamic, patient specific models using an open-source software for dynamic simulations of human movement. Inverse kinematics techniques were used to calculate joint angles and spatiotemporal gait parameters. Preliminary results suggest that high levels of body weight support cause large differences in lower extremity joint angles, particularly at the ankle. Percentage of stance during the gait cycle appears to decrease with increased body weight support, and also with increased speed. These data suggest that walking with very high levels of body weight support may not replicate normal walking conditions closely enough to produce the most effective rehabilitation strategy. The results of this study will shed insight into which BWSTT conditions cause gait kinematics to deviate from those seen in normal walking patterns. Determining the affect of specific training conditions will help therapists make more informed decisions when setting treadmill speed and body weight support levels, which could lead to the development of more efficient rehabilitation programs.
Macrophage Migration Inhibitory Factor: A Key Mediator of Inflammation
(2009-04) Kithcart, Aaron; Whitacre, Carol
Multiple sclerosis (MS) is a demyelinating neurological disease affecting more than 400,000 Americans, causing progressive motor and sensory loss. MS is typically diagnosed during the second and third decades of life and thus is the primary cause of non-traumatic disability in the United States. The pathology of MS involves activation of autoreactive lymphocytes and their migration across the blood-brain barrier (BBB) into the central nervous system (CNS), including both the brain and spinal cord. It has been previously reported that MS patients have a higher level of the ubiquitously expressed, proinflammatory molecule MIF. We have shown that mice lacking MIF have fewer leukocytes in the CNS following induction of experimental autoimmune encephalomyelitis (EAE), an animal model for MS. We therefore hypothesized that MIF was a critical mediator of leukocyte trafficking. The purpose of this study was to determine the biological source of MIF and whether an inhibitor of MIF could reduce trafficking. We found using a combination of adoptive transfer and bone marrow chimera studies that mice expressing MIF from myeloid cells had significantly more severe disease than MIF KO mice or mice expressing MIF only in non-myeloid cells. Monocytes and microglia are derived from myeloid cells and thus we believe are the critical sources of MIF. Indeed, using immunohistochemistry, we found more infiltrates in the CNS of mice when myeloid cells expressed MIF. We followed up this study by utilizing a small molecule inhibitor of MIF to evaluate whether disruption of MIF activity could inhibit lymphocyte migration. Mice had reduced severity of EAE following inhibitor administration and reduced migration of leukocytes into the CNS. Other groups have shown that blocking MIF reduces expression of adhesion molecules on the BBB. Our data suggests that during inflammatory disease, MIF from myeloid cells is critical for leukocyte migration and an inhibitor of MIF reduces migration and subsequent clinical disease. This drug could be a potential new therapeutic option for the millions of patients suffering from multiple sclerosis worldwide.
INTERNATIONAL ACQUISITIONS BY INDIAN FIRMS - SYNERGY, MANAGERIALISM OR HUBRIS?
(2009-04) Singh, Suresh; Shenkar, Oded
Emerging economy firms are increasingly acquiring foreign firms, either buoyed by success at home or as a response to competitive threats from foreign players entering their home markets. These firms are new to the game and it remains to be seen if they have been able to secure gains for their shareholders in the process. This study analyzed international acquisitions by Indian firms and found that shareholder gains are positive overall. However, larger firm size tends to have a negative impact on shareholder returns suggesting that bigger firms may be prone to hubris. Managerialism was not found to be a significant.
Polylysine modified hydrogels: brain mimetic materials for neural tissue engineering
(2009-04) Rao, Shreyas; Winter, Jessica
Disorders arising from central nervous system (CNS) damage affect over a million individuals in the United States each year. Unfortunately, the CNS neurons do not possess regeneration potential under normal conditions. To address these issues, researchers have developed biomaterials that function as regenerative scaffolds or are incorporated into neural prosthetic devices (e.g., deep brain stimulators). Neural biomaterials primarily consist of natural or artificial polymeric materials. Natural materials can replicate the native tissue environment very well; however manipulating their properties may be difficult. On the other hand, synthetic materials chosen for their tunable properties do not favor neural cell adhesion, a process which initiates neural regeneration. To improve the compatibility of synthetic materials, it is vital to enhance their cell adhesive capability, which would also improve biomaterial-tissue integration. To achieve these goals, we have developed synthetic hydrogels, cross linked, hydrophilic polymeric materials, that closely mimic the native brain tissue. Further, we have incorporated the non-native cell adhesion molecule polylysine into the backbone of poly (ethylene glycol)-diacrylate (PEG-DA) hydrogels using standard bioconjugation techniques. Briefly, unmodified PEG-DA hydrogels were prepared through UV photocrosslinking. Polylysine was conjugated to Acryl-PEG-N- hydroxysuccinimide (Acryl-PEG-NHS) using standard NHS chemistry. The resulting Acryl-PEG-Polylysine was incorporated into PEG-DA hydrogels using UV photocrosslinking. Polylysine conjugation was monitored by observing the diffusion of fluorescent FITC-polylysine over a period of one week against a negative control (no polylysine) and a sham (unconjugated polylysine) using a fluorescent plate reader. PC12 (a model cell line for studying neural behavior) cell response (i.e., neural adhesion) to polylysine conjugated materials was then assessed against suitable controls. Live-dead staining was employed to quantify neural cell adhesion on modified hydrogel materials. It was observed that cell adhesion molecule-modified hydrogels promote PC12 cell adhesion and hence can be used extensively in neural tissue engineering applications to promote neural regeneration. Additionally, these materials could be employed as surface coatings for neural stimulation or recording electrodes to improve electrode-tissue biocompatibility and enhance device performance.
The Measure of Literacy in Later Medieval England
(2009-04) Bennett, James; Hanawalt, Barbara
In the mid-thirteenth century, the tenants living on the manors of the liberty of St Albans had no use for letters. Whenever they had need to pledge marriage vows, declare their last will and testament, or buy or sell land and property, only their spoken words served to seal their promises. “Truth,” as they understood it, resided in the character of the person who solemnly swore to it; by their nature, good men and women embodied the truth, while those renowned for poor character could never claim it. When jurors heard the testimony of litigants in court, they based their decisions on the relative good repute of the opposing parties, for the “facts” of a case could not be disentangled from the moral standing of those persons who spoke them. The tenants had adhered to this system from time out of mind. Since it worked effectively to solve disputes, they no doubt imagined that they always would. Yet in the first decades of the fourteenth century, the tenants of St Albans began to adopt a new evidentiary standard in court that would not only change the procedures used therein, but would transform their approaches to a host of extra-judicial concerns. While jurors selected from among the laypeople judged the cases at the manor courts, the monks who owned the manors administered the courts and kept copious written records of the proceedings. Ever so slowly, over the course of years, tenants learned that these records could be used successfully to challenge the truth claims of oral witnesses. Those who adopted these procedures generally won their cases. These litigants may have never learned to read, but they did learn the power of writing. More profoundly, they learned that truth could reside not just in the content of one’s character, but could also take form in symbols etched onto a lifeless scrap of parchment. That realization gave them the confidence and evidence needed to challenge traditional authorities in manners not previously imaginable. In courts of law, men popularly assumed to be of poor character could now disprove the word of their social betters. Women could now successfully challenge the verdicts of the men who served as their jurors. Most flamboyantly, the tenants could now assemble legal evidence to overturn the ancient privileges of their monastic lords. When those cases did not find verdicts in accordance with the evidence, the tenants violently rebelled. The adoption of literate practices did not turn the world of the Liberty of St Albans upside down, but it did make previously stable and explicitly vertical personal and corporate power relationships into far more topsy-turvy structures. The process that undermined those once firm social structures forms the subject of my dissertation and of this presentation.
Development of heat-sensitive microbubbles for cancer ablation margin assessment
(2009-04) Huang, Jiwei; Xu, Ronald
Thermal ablation processes hold the promise of less invasive cancer management. But broader acceptance of cancer ablation processes is hindered by controversial issues and concerns due to the lack of effective assessment of the ablation margin during surgery. We developed heat-sensitive microbubbles for ablation margin assessment during a cancer ablation surgery. The heat-sensitive microbubbles, which comprise a core of liquid perfluorocarbons (PFC) within a biodegradable poly lactic-co-glycolic acid (PLGA) shell, were fabricated using an emulsion evaporation method. Optical microscopic imaging showed that, at the boiling point of PFC (55ºC), the microbubbles expanded from 1 μm to 20 μm due to PFC evaporation. Additionally, the microbubbles were embedded in a tissue simulating phantom made of agar-agar gel for ultrasound imaging. At room temperature, the microbubbles were not detected by the ultrasound. After being evenly heated to 55 ºC for 10 minutes, the microbubbles were clearly visualized by the ultrasound. These results demonstrate that the heat sensitive microbubbles can be potentially utilized as an ultrasound contrast agent for thermal ablation margin assessment. Successful implementation of these heat-sensitive microbubbles may enhance the accuracy for cancer ablation and revolutionize the clinical practice of cancer management.
A Model-Based Analysis of Anxiety and Biased Processing of Threatening Information
(2009-04) White, Corey; Ratcliff, Roger
The present study employed a decision model to explore processing biases in anxiety. Anxious individuals show preferential attention to threatening compared to neutral information, which can serve to maintain or increase levels of anxiety. Several models of anxiety predict biased processing of threat under most circumstances, but previous research has failed to demonstrate a threat bias in certain tasks involving word recognition and memory. This has been taken by some researchers as evidence that the threat bias is dependent on contextual factors. An alternative explanation is that threat bias is present in these tasks, but analytical methods are not sensitive enough to detect small differences. The present study was designed to determine if threat bias could be shown in word recognition and memory tasks. Individuals with high and low levels of anxiety were compared in their responses to threatening words. Behavioral data were analyzed with the diffusion model, a quantitative model of decision processes that provides a more sensitive measure of processing than traditional measures, response times and accuracy. The diffusion model analysis showed that the high-anxiety participants had consistent advantages for early processing of threatening words, but disadvantages for later memory of threatening words. The results from these experiments are consistent with several models of anxiety, with anxious individuals showing initial vigilance in the detection of threat, but avoidance of deeper processing of threatening information. The improved sensitivity of the model-based analysis suggests that previous failures to show threat bias might have been due to use of imprecise dependent measures. By demonstrating threat bias in these tasks, there is no longer a need for ad hoc explanations of why the bias does not occur in certain conditions, allowing for more parsimonious models of anxiety.
Understanding the Drivers of Firm-level Stock Returns: An International Perspective
(2009-04) Chen, Jia; Stulz, Rene
At social occasions, economists are often asked to interpret the movement of stock returns. In response, they have developed theories that break unexpected stock returns into changes in expectations of future cash flow and changes in expectations of future returns. Intuitively, one can call the former "news about future cash flow", or cash-flow news, and the latter "news about future returns", or expected-return news. It helps to understand how stock returns move to examine which news component is more important in terms of driving stock returns. By using US firms, researchers have empirically documented that cash-flow news dominates expected-return news in terms of explaining the variance of unexpected stock returns. However, little effort has been spent on understanding how the relative importance of these two news components varies with other economic factors, such as market opaqueness, financial market development, and investor protection. An international setting offers opportunities to understand the link between these country characteristics and the relative importance of news components. As a first step toward this goal, this paper uses the vector autoregressive model (VAR) developed by Campbell (1991) and Vuolteenaho (2002) to decompose firm-level stock returns for 29 countries around the world. By using a country-level earnings management measure developed by Leuz et al. (2003), we find that expected-return news is more important in driving unexpected stock return in countries where the earnings management is more extensive.
Looming Maladaptive Style as a Specific Moderator of Risk Factors for Anxiety
(2009-04) Adler, Abby; Strunk, Daniel
Both the tendency to view threatening events as likely and the experience of threatening events have been identified as important in the etiology and maintenance of symptoms of anxiety. However, these risk factors have also been related to the course of depressive symptoms. In an effort to expand on traditional theories of anxiety, Riskind (1997) proposed that an individual’s tendency to view threatening events as rapidly intensifying and approaching is an important, though often neglected factor in understanding anxiety. This tendency is known as a looming maladaptive style (LMS). Studies have shown that LMS predicts subsequent change in symptoms of anxiety (e.g., Riskind, Williams, Gessner, Chrosniak, & Cortina, 2000), and distinguishes between individuals diagnosed with Generalized Anxiety Disorder, Major Depressive Disorder, and controls (Riskind & Williams, 2005). Given the limitations of traditional risk factors for anxiety and more recent findings by Riskind, I sought to examine whether LMS is a specific moderator for predicting change in anxiety symptoms (as compared to depressive symptoms) over one month. I considered two interactions in predicting change in anxiety: first, an interaction of predictive tendencies for threatening events and LMS, and second, an interaction of experiencing threatening events and LMS. Interactions indicate that the combination of two risk factors predicts substantially more risk than either risk factor alone. Seventy-two undergraduates with a range of anxiety and depressive symptoms completed measures at five times points. Anxiety and depressive symptoms were assessed via self-report and interview-based measures at the initial session as well as one-month follow-up. In addition, participates completed a measure of LMS and made predictions for the likelihood that 10 threatening events would occur to them over the following month. Assessments of threatening life event occurrence were collected online from participants weekly. First, predictive tendencies and experiences of threatening events were each significant predictors of change in anxiety over one month. Thus, greater predictive tendencies for threatening events or more threatening events occurring were each related to a worse course of anxiety symptoms. Second, the interactions of (1) predictive tendencies and LMS and (2) experiences of threatening events and LMS were each significant in predicting change in anxiety. Thus, considering these interactions accounted for significantly more variance than merely considering each predictor independently. Furthermore, these interactions remained significant in predicting change in anxiety even after covarying residualized change in depressive symptoms. Finally, when change in depression was the primary dependent variable, these interactions were not significant. These results suggest that the interaction of predictive tendencies and LMS as well as the interaction of experiences of threatening events and LMS appear specific for predicting change in symptoms of anxiety (as compared to symptoms of depression). When people exhibit a high LMS, the relationships between more traditional risk factors and symptoms of anxiety are particularly strong, suggesting that LMS is a key vulnerability factor that may be the focus of early interventions for anxiety disorders.
Genetic Contributions of the Tumor Microenvironment in Breast Cancer Metastasis
(2009-04) Werbeck, Jillian; Rosol, Thomas
Metastasis is a multistage process involving many complex genetic events which facilitate the spread and growth of cancer cells at a secondary site. In vivo models of metastasis are invaluable to our understanding of the interactions between cancer cells and a variety of cell types at the metastatic microenvironment. The objective of this study is to first understand how different in vivo models of metastasis can affect the site of secondary growth and second, to identify the genetic changes that occur in a single population of cancer cells at various metastatic microenvironments. For this study, we used a cell line derived from the commonly used and highly metastatic MMTV-PymT murine breast cancer model. In order to accurately model metastasis as a multi-step process we injected the PymT breast cancer cells via 5 different routes of inoculation. Subcutaneous, orthotopic (mammary fat pad), intravascular (tail vein and intracardiac), and intratibial injections allow us to assess the metastatic pattern of this cell line along different stages in the metastatic cascade. In order to evaluate patterns of dissemination, tumor cells were tracked over time using a Xenogen In Vivo Imaging System (IVIS). Termination criteria were based on clinical symptoms of metastasis and therefore mice were sacrificed accordingly based on tumor burden and/or other signs of pain or distress. Metastases were evaluated based on histopathology, radiographic evaluation, and gross necropsy. The genetic profile of the tumor was compared at various organ sites (subcutis, mammary fat pad, lung, ovary, adrenal gland, tibia) using a RT2 Profiler™ PCR Array System, Superarray Bioscience Corporation (N=3). We found that the route of injection did affect the dissemination of PymT tumor cells. We found no metastasis after mammary fat pad injection (N= 0/10), or subcutaneous injection (N= 0/10). Lung metastases were commonly detected after tail vein injection (N= 9/11), along with ovary metastases in a smaller percentage of mice (N= 2/11). Interestingly, alternative intravascular routes of injection (intracardiac) resulted in a different pattern of dissemination: ovary (N= 13/20), adrenal gland (N= 6/20), and bone (N= 3/20). Finally, no metastases were observed following intratibial injections although mild osteolysis was visible via radiographic and histologic evaluation. In addition, the MMTV-PymT tumor cells had different genetic profiles depending on their site of growth (p<0.01). Specifically, E-cadherin, FGFR1, EGF, and MMP9 expression were greater than 3 fold different in PymT metastases when compared to the cells in the mammary gland control. We demonstrated that the tumor microenvironment has a site-specific effect on the gene expression profile of the PymT cell line. Interestingly, we have also shown that the injection route may significantly affect the metastatic potential of tumor cells, and therefore the pathology of secondary lesions. This study has significant implications in trying to understand the mechanism by which tumor cells disseminate, and also the genetic interactions between tumor cells and stroma in various organs of metastasis.
Automation of Delivery Device for Chlorine Dioxide Disinfection
(2009-04) Vedachalam, Sridhar; Mancl, Karen
Although water reuse has been practiced in many countries for centuries, severe water scarcity in many parts of the world has aroused renewed interest. In addition, the health risks posed by untreated wastewater emphasize the need to prevent the spread of fecal-oral pathogens through adequately disinfecting wastewater. Though chlorine has widely been used as a disinfectant, its inability to inactivate certain microorganisms and its role in the formation of cancerous trihalomethanes has created the search for alternatives. Chlorine-dioxide has been found to be an effective replacement, though it poses some inherent safety issues being explosive at concentrations of 10% (w/w) or more, sensitive to pressure, and somewhat toxic to juvenile fish. Small packets of precursor chemicals are now commercially available to generate small quantities of chlorine dioxide onsite. The aim of this research was to develop an automated delivery device for dispensing this disinfectant in the form of a packet, which would strongly mitigate safety issues and make the dispenser user-friendly. The automation of the delivery device involved the design of a 30-slot Geneva mechanism to drop the packet into a chamber. This packet-dropping mechanism was designed for use both in a manual mode, requiring no use of electricity, and an automated mode, powered through electricity. A fully functional prototype was built to demonstrate the automation of a disinfection delivery device. Disinfected water is safe for discharge on open lawns and gardens, since the chlorite ion, a byproduct, is present in low concentrations. However, wastewater discharge and reuse may be subject to local or state regulations.
RAPID QUANTIFICATION OF DIPICOLINIC ACID FROM SPORES TREATED BY PRESSURE-ASSISTED THERMAL PROCESSING USING INFRARED SPECTROSCOPY
(2009-04) Prabhakar, Veena; Rodriguez-Saona, Luis E
Endopores (or spores), which are produced by certain bacteria, are capable of surviving food processing and causing food spoilage and foodborne illness. Dipicolinic acid (DPA), which constitutes about 10% of the spores’ dry weight, plays a major role on wet heat resistance of spores. Current methods like chromatography and fluorometry that are used to quantify DPA are time-consuming, expensive and use hazardous solvents. Rapid methods to quantify the DPA levels in spores would enable simple and cost-effective approaches to study spore inactivation during thermal and non-thermal food processing. FTIR spectroscopic analysis was used to build a regression model that could be used for rapid prediction of DPA content released from treated Bacillus spores. Bacillus amyloliquefaciens FAD82 cultures were treated by pressure-assisted thermal processing with sampling at different time intervals. Aliquots (1mL) of the processed samples were centrifuged and the supernatant was analyzed using a fluorometer (reference method) to determine the released DPA concentration. Pellets were dried on a hydrophobic grid membrane filter and scanned using FTIR spectrometer. The collected spectra were correlated with the DPA concentrations obtained from the fluorometer to develop regression model based on partial least square regression analysis. The regression model was able to predict the DPA concentrations with a standard error of 6 µM. This method proved to be simple, rapid and accurate, without the need for expensive and hazardous chemicals.
Intraoperative Fluorescence Surgical Goggle
(2009-04) Qin, Ruogu; Xu, Ronald
Background Malignant tissue resection, especially tumor resection is a great challenge to surgeons. Due to the disseminated characteristic of these tissues, the small and varied foci and blurred margins often evade surgeon’s unaided eyes. Unfortunately, surgeons have to rely mainly on preoperative images and their experience. No effective method is available that can provide real-time reference. Based on targeted fluorescence contrast agents, we are developing an intraoperative imaging system (surgical goggle) for identifying locations and margins of tumors. Method Tumor targeted MuCC49-Cy7 is injected into a female athymic nude mice. We use light at a near infrared (NIR) range (710 – 760nm) to excite the fluorophore. An ICG filter (810-875nm) is used to collect fluorescence from MuCC49-Cy7 in vivo. Also, non-fluorescence image is acquired immediately after the fluorescence image with the illumination of light at longer wavelength. Two images are processed, merged then sent to a Head Mounted Display (HMD, vision goggle) for virtual reality display. To validate the accuracy of the system, we use surgical goggle to perform mice anatomy and visualize fluorescence in vitro. Result The emission fluorescence is not detectable with bare eyes since it is in the NIR range that provides deeper penetration. However, with the help of surgical goggle, we are able to clearly identify locations and margins of tumors on the mice. At the 1st day after IV injection of MuCC49-Cy7, we can visualize dispersive fluorescence. At the 3rd day after the injection, fluorescence mainly accumulates at tumor sites. Mice anatomy validates that the merged image correctly delineate tumors. Conclusion Our surgical goggle can provide real-time, intraoperative reference during surgery. It is a robust and reliable method for segmenting and subsegmenting tumor.
Parenthood, Life Course Expectations, and Mental Health
(2009-04) Carlson, Daniel; Williams, Kristi
Although past research indicates that births at young ages and births prior to marriage may negatively affect parents’ mental health, little is known about the role personal expectations for first birth timing and sequencing have in shaping these associations. Using data from the National Longitudinal Survey of Youth 1979 (NLSY79), I examine how personal expectations in young adulthood for first birth timing and sequencing condition the associations between age at first birth, pre-marital first births, and parents’ mental health. I also examine whether the conditioning effects of expectations vary by race/ethnicity. Results indicate that, in most cases, the relationship between age at first birth, pre-marital first births, and mental health varies according to whether first birth timing and sequencing violates personal expectations for the transition into parenthood, however, these effects are not universal. The conditioning effects of expectations differ for African-Americans compared to non-Hispanic whites.
Exposure and Vulnerability: Child Health as a Vector in the Intergenerational Transmission of Social Position
(2009-04) Lynch, Jamie; Downey, Doug
This study investigates the role of child health in the intergenerational transmission of status and the formation of health disparities in educational outcomes prior to formal schooling. Using data from the Early Childhood Longitudinal Study – Birth Cohort, child health is hypothesized to be a product of parental socioeconomic status and race, and to subsequently impact cognitive development, math, and reading prior to kindergarten. In addition race and parental investment are, respectively, hypothesized to moderate and mediate the negative influence of poor child health on learning. Results find evidence of health disparities in cognitive development, math, and literacy skills originating just nine months after birth. Poor child health proves to be an equal opportunity delayer, as children with poor health and racial minority status do not suffer a double disadvantage in early cognitive development. Overall, results emphasize the importance of child health as a critical factor in the intergenerational transmission of social status.
Forecasting product returns for production planning and control in remanufacturing
(2009-04) Clottey, Toyin; Benton, W. C.
There is a growing focus on sustainability in corporate objectives. A key approach to managing and implementing sustainability is through operations management. Sustainable operations hold the key to increased profitability and effective management of environmental issues. Among the business processes used for sustainability is reuse. A key preferred component of reuse is remanufacturing. Legislation trends, as evidenced in the European Union, are forcing manufacturers to take back and put products back into the market, after remanufacturing. The remanufacturing may be done by either the manufacturer or a remanufacturer. In this study, we consider a manufacturer that also acts as a remanufacturer, and develop a generalized forecasting approach to determine the returns of used products, as well as integrate it with an inventory model to enable production planning and control.

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