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Protein adducts and crosslinking by reactive metabolites of polychlorinated biphenyls (PCBs)Li, Miao 01 December 2015 (has links)
Polychlorinated biphenyls (PCBs) are the persistent environmental pollutants with the continuous concerns over adverse human health effects. As semi-volatile compounds, PCBs were found in indoor and outdoor air. The observation of high levels of airborne PCBs in old school buildings raised the concerns of inhalation exposure and toxicity of PCBs. Lower chlorinated PCBs (LC-PCBs), major components of airborne PCBs, are subject to biotranformation. In vitro and in vivo studies revealed that reactive metabolites of LC-PCBs formed covalent adducts on DNA and proteins. The hypothesis of the project is that the reactive metabolites of LC-PCBs are able to form adducts on proteins or even protein crosslinks, and the formation of protein adducts and crosslinks causes the dysfunction of the target proteins. In addition, the objectives of the project are also to identify protein targets by PCB metabolites, which may be related to the mechanism of toxicity of LC-PCBs. The alkaline permethylation (AP) was established and optimized to identify and measure the protein adducts from LC-PCB metabolites. The AP method evidenced PCB metabolites formed protein adducts through the sulfhydryl groups and also one molecule of PCB quinoid metabolites was able to bind to more than one protein. Application of cytochrome c as the model protein revealed PCB quinoid metabolites also formed adducts on lysine and glutamic acid. The adduct formation and crosslinks caused the dysfunction of cytochrome c. In addition, the quinone protein adducts still kept the ability for redox reactions, which may lead to unexpected toxicity. The SILAC method was applied to identify the target proteins in the samples of in vitro proteome incubation. The instability of PCB quinone protein adducts was found by further reaction of quinone protein adducts. This may be the reason why cysteine-PCB quinone adducts were not frequently identified by proteomics method. The further understanding of protein adducts by reactive PCB metabolites helps to identify the target proteins, and ultimately reveal the role of protein adducts impacting on human health.
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Teacher attributions, expectations, and referrals for students involved in the child welfare and juvenile justice systemsAnthony, Stephanie Nichole 01 December 2014 (has links)
The primary purpose of this study was to examine differences in the attributions teachers make toward students in the child welfare and juvenile justice systems. The study utilized vignettes and asked teachers to attribute the responsibility for declines in behavior and academic performance to one of five sources (the student, the parents, the teacher, the court system, or the student's friends). The study further asked teachers to identify the extent to which the changes were due to the student's internal traits and external factors, the likelihood of changes in behavior and academic performance with and without intervention, the teachers' beliefs about their ability to impact change, the amount of time the teachers reported being willing to spend with the students outside of class, and the likelihood of the student pursuing post-secondary education. Teachers were also asked to identify to whom they would first refer the student in the vignette for outside assistance due to declines in behavior and academic performance and then provide all referrals they would make.
A total of 224 certified 6th -12th grade teachers in the state of Iowa completed the vignette survey between January 2014 and April 2014. Results indicated that teachers made different attributions toward students on the basis of their involvement in either the child welfare or juvenile justice system. Specifically, teachers attributed the reason for behavioral and academic declines to different sources for students in the child welfare system, the juvenile justice system, and the control condition. Teachers were more likely to attribute academic and behavioral declines to internal factors for students in the juvenile justice system and external factors for students in the child welfare system. Teachers reported students in the juvenile justice system as least likely to change without intervention. The majority of teachers across the three conditions indicated their first referral would be to mental health services within the school. Teachers did not differ in the total number of referrals made, the amount of time until making the referral, the amount of time they would be willing to spend with the student outside of class time in order to impact change, their feelings of efficacy to impact change, and the likelihood of the student obtaining post-secondary education. Finally, limitations of the study are presented, suggestions for future research are discussed, and the implications of this study for teachers and school psychologists are discussed.
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Copper-zinc superoxide dismutase and glucose metabolism as redox targets for bortezomib resistance in multiple myelomaSalem, Kelley 01 December 2014 (has links)
Multiple myeloma (MM) is a prevalent B-cell neoplasm that remains incurable with currently available chemotherapeutic drugs. Existing drug regimens result in initial disease remission but MM often relapses with an aggressive, drug resistant phenotype with uniform mortality. Bortezomib (BTZ, proteasome inhibitor) is a frontline anti-MM drug that is used for treatment of newly diagnosed and relapsed MM. However both intrinsic and acquired BTZ resistance is observed. Hence, gaining a mechanistic understanding of BTZ-resistance can provide novel targets to increase and restore BTZ cytotoxicity in MM. Studies show that BTZ-mediated proteasome inhibition generates oxidative stress therefore, BTZ resistance can be caused by an increase in cellular antioxidant capacity of MM cells. Antioxidants like superoxide dismutases (SODs), glutathione (GSH), and glutathione peroxidases (GPxs) can maintain cellular redox homeostasis and confer resistance to oxidative stress. Additionally, an increased glucose metabolism can assist in maintaining low reactive oxygen species (ROS) levels formed as by-products of endogenous or therapy induced oxidative stress. This led us to test the hypothesis that BTZ resistance in MM is linked to redox regulation via the antioxidant network and generation of reducing equivalents. Retrospective analysis of clinically annotated MM dataset shows a correlation between SOD1 gene expression, MM progression, and poor overall and event free survival. In a MM cell line model with intrinsic or acquired BTZ resistance, our results show a correlation between half maximal inhibitory concentration (IC50) of BTZ and CuZnSOD activity. Upon inhibition of CuZnSOD activity with a clinically approved drug, disulfiram (DSF, Antabuse), BTZ cytotoxicity was increased. Furthermore, enforced overexpression of CuZnSOD conferred BTZ resistance in an otherwise BTZ sensitive MM cell line. MM cell lines with differential intrinsic BTZ cytotoxicity displayed a correlation between BTZ IC50 and GSH levels as well as GPx-1 activity. Gene expression profiling data from patients showed that poor prognosis associates with increased glycolytic gene expression in MM. Also, MM cell lines with intrinsic resistance toward BTZ exhibited increased glucose uptake, increased mRNA expression and activity of glucose-6-phosphate dehydrogenase (G6PD) with increased cytotoxicity with glucose deprivation or 2-deoxyglucose (2-DG) treatment. In conclusion, our results provide a rationale for utilizing redox-based combination protocols of clinically approved drugs (i.e. DSF and 2-DG) with BTZ to improve MM therapy responses.
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Behavioral and neurophysiological investigations of short-term memory in primatesBigelow, James 01 May 2015 (has links)
Detecting and interpreting sensory events, and remembering those events in in the service of future actions, forms the foundation of all behavior. Each of these pillars of the so-called "perception-action cycle" have been topics of extensive inquiry throughout recorded history, with philosophical foundations provided by early BCE and CE periods (especially during the Classic and Renaissance eras) leading to intensive empirical study in the twentieth and twenty-first centuries. Such experiments have described detailed (but incomplete) behavioral functions reflecting perception and memory, and have begun to unravel the extraordinarily complex substrates of these functions in the nervous system. The current dissertation was motivated by these findings, with the goal of meaningfully extending our understanding of such processes through a multi-experiment approach spanning the behavioral and neurophysiological levels. The focus of these experiments is on short-term memory (STM), though as we shall see, STM is ultimately inseparable from sensory perception and is directly or indirectly associated with guidance of motor responses. It thus provides a nexus between the sensory inputs and motor outputs that describe interactions between the organism and environment.
In Chapter 2, previous findings from nonhuman primate literature describing relatively poor performance for auditory compared to visual or tactile STM inspired similar comparisons among modalities in humans. In both STM and recognition memory paradigms, accuracy is shown to be lowest for the auditory modality, suggesting commonalities among primate species. Chapters 3-5 examined STM processing in nonhuman primates at the behavioral and neurophysiological levels. In Chapter 3, a systematic investigation of memory errors produced by recycling memoranda across trials (proactive interference) is provided for the understudied auditory modality in monkeys. Such errors were ameliorated (but not completely eliminated) by increasing the proportions of unique memoranda presented within a session, and by separating successive trials by greater time intervals. In Chapter 4, previous results revealing a human memory advantage for audiovisual events (compared to unimodal auditory or visual events) inspired a similar comparison in monkeys using a concurrent auditory, visual, and audiovisual STM task. Here, the primary results conformed to a priori expectations, with superior performance observed on audiovisual trials compared to either unimodal trial type. Surprisingly, two of three subjects exhibited superior unimodal performance on auditory trials. This result contrasts with previous results in nonhuman primates, but can be interpreted in light of these subjects' extensive prior experience with unimodal auditory STM tasks. In Chapter 5, the same subjects performed the concurrent audiovisual STM task while activity of single cells and local cell populations was recorded within prefrontal cortex (PFC), a region known to exhibit multisensory integrative and memory functions. The results indicate that both of these functions converge within PFC, down to the level of individual cells, as evidenced by audiovisual integrative responses within mnemonic processes such as delay-related changes in activity and detection of repeated versus different sensory cues. Further, a disproportionate number of the recorded units exhibited such mnemonic processes on audiovisual trials, a finding that corresponds to the superior behavioral performance on these trials. Taken together, these findings reinforce the important role of PFC in STM and multisensory integration. They further strengthen the evidence that "memory" is not a unitary phenomenon, but can be seen as the outcome of processing within and among multiple subsystems, with substantial areas of overlap and separation across modalities. Finally, cross-species comparisons reveal substantial similarities in memory processing between humans and nonhuman primates, suggesting shared evolutionary heritage of systems underlying the perception-action cycle.
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Effects of polyploidy and reproductive mode on life history trait expressionLarkin, Katelyn 01 May 2015 (has links)
Although genomes are perhaps the single most important element of living systems, why they feature such striking variation and how this variation is maintained within and across natural populations remains unclear. One of the most common and important means by which genomic variation is generated is ploidy elevation. While polyploidy has been implicated in the remarkably successful radiations of angiosperms, teleost fish, and amphibians, the phenotypic consequences of changes in ploidy level are poorly understood, especially in animals. I use a large, multi-year common garden experiment to identify potential life history costs and benefits of polyploidy and asexual reproduction, a trait often associated with polyploidy, in Potamopyrgus antipodarum. This snail is well suited for studying ploidy variation and sex because diploid sexuals and triploid and tetraploid asexuals frequently coexist, allowing us to use comparisons of sexuals to asexuals and triploid to tetraploid asexuals to study both the effects of ploidy elevation and sex. I detected a strong negative correlation between growth rate and time to maturity and found that sexual P. antipodarum grew and matured significantly more slowly than the polyploid asexuals. Sexual P. antipodarum were also more likely to die before achieving reproductive maturity than their asexual counterparts. By contrast, there were no apparent life history differences between triploid and tetraploid asexuals, indicating that direct phenotypic benefits of ploidy elevation are unlikely to explain the relatively rapid growth and maturation of asexuals. My results suggest that ploidy elevation does not inevitably confer phenotypic consequences, that reproductive mode influences life history trait expression, and that sexual P. antipodarum persist in many natural populations in spite of substantial life history disadvantages.
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Universal deformation rings and fusionMeyer, David Christopher 01 July 2015 (has links)
This thesis is on the representation theory of finite groups. Specifically, it is about finding connections between fusion and universal deformation rings.
Two elements of a subgroup N of a finite group Γ are said to be fused if they are conjugate in Γ, but not in N. The study of fusion arises in trying to relate the local structure of Γ (for example, its subgroups and their embeddings) to the global structure of Γ (for example, its normal subgroups, quotient groups, conjugacy classes). Fusion is also important to understand the representation theory of Γ (for example, through the formula for the induction of a character from N to Γ).
Universal deformation rings of irreducible mod p representations of Γcan be viewed as providing a universal generalization of the Brauer character theory of these mod p representations of Γ.
It is the aim of this thesis to connect fusion to this universal generalization by considering the case when Γ is an extension of a finite group G of order prime to p by an elementary abelian p-group N of rank 2. We obtain a complete answer in the case when G is a dihedral group, and we also consider the case when G is abelian. On the way, we compute for many absolutely irreducible FpΓ-modules V, the cohomology groups H2(Γ,HomFp(V,V) for i = 1, 2, and also the universal deformation rings R(Γ,V).
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Visual design for the entertainment industry and beyondIngram, Lucas Peter 01 May 2016 (has links)
A visual investigation into the lighting, scenic and projection design work of Lucas P. Ingram during his training at the University of Iowa from 2013 – 2016.
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Feasibility for spinal muscles creating pure axial compressive load or follower load in the lumbar spine in 3-D posturesWang, Tianjiao 01 May 2015 (has links)
Previous in-vivo studies showed that compressive force acting on the spine may exceed 2600 N. However, the ligamentous lumbar spine becomes unstable when subjected to compressive loads less than 100 N. It is generally accepted that the ligamentous spine itself is unstable but can be stabilized by muscle forces (MFs) in vivo. Nevertheless, normal spinal muscle contraction patterns remain unknown.
In recent in vitro studies, when the direction of the applied load was controlled along the spinal curvature so that the internal spinal load became perfect compressive follower loads (CFLs) at all lumbar levels, the ligamentous lumbar spine was found to withstand large compressive load (up to 1200 N) without buckling while maintaining its flexibility in neutral or flexed postures. The results of in-vivo animal studies also have shown that shear stress has a more detrimental effect on the rate of disc degeneration compared to compressive stress. These results suggest CFLs in the lumbar spine would be a normal spinal load whereas the transverse (or shear) load abnormal. An initial test of this postulation would be to investigate whether the spinal muscles can create perfect internal CFLs in the lumbar spine in all 3-D postures. In addition, small intrinsic muscles (SIMs) are crucial for better control of the direction of the internal spinal load along the spinal axis was also proposed.
A finite element (FE) model together with an optimization model were used for this study. Both models consist of the trunk, sacrolumbar spine and 244 spinal muscles. Different from other studies, 54 SIMs were also included in the models. The FE model was validated by comparing the ROM of the spine with the literature data. Minimization of the summation of the spinal loads and moments was used as the cost function for the optimization model. The geometrical data obtained from the FE model was used as the input for the optimization model; it was then used to calculate the MFs required for creating the CFLs at all lumbar spine levels. The MFs determined in the optimization model were then imported back to the FE model as input loads to check the stability of the spine under this loading condition. Five different postures were studied: neutral, flexion 40°, extension 5°, lateral bending 30° and axial rotation 10°.
Many optimization solutions for spinal muscle force combinations creating pure CFLs in the lumbar spine were found available in each posture. However, FE analyses showed that only muscle forces and patterns solved at FLPs along the curve in the vicinity of the baseline curve stabilized the lumbar spine. Stability was determined by small displacement of the trunk (less or equal to 5mm) due to small deformation of the lumbar spine. The magnitudes of joint reaction forces (JRFs) predicted from the optimization model were comparable to those reported in the literature. When the SIMs were removed, optimization solutions were still feasible in all five postures, but JRFs and trunk displacement were increased. This suggests the need of SIM inclusion in future spine biomechanics studies and clinically, damages to the SIMs may have a high risk of future spinal problems, such as spinal instability, early disc degeneration, deformity and/or early failure of spinal fixation devices.
The results from this study supported the hypothesis that the perfect CFLs at all lumbar levels could be the normal physiological load under which the lumbar spinal column could support large load without buckling while allowing flexibility. SIMs played an important role in creating CFLs as by including SIMs in the models, the JRFs at all lumbar spine levels were lowered and the stability of the spine was increased.
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Status, racial hegemony, and phenotypical inequality: exploring the racial invariance hypothesisBiagas, David Edward, Jr 01 July 2015 (has links)
Social psychological theorizing assumes that 1) members of dominant and oppressed racial groups subscribe to the same set of cultural beliefs regarding the racial hierarchy in the United States and 2) that patterns of deference in task groups reflect broader patterns of inequality in society. With the use white and black research participants at two research sites, this thesis examines these assumptions with regards to the proposed tri-racial hierarchy of the Latin Americanization Thesis, which asserts that the racial hierarchy in the U.S. is now primarily determined by phenotype, as opposed to traditional racial and ethnic boundaries.
Do White and Black Americans associate similar perceptions of status with members of the proposed tri-racial hierarchy? In addition, skin tone is associated with socioeconomic status among blacks in the U.S., but do research participants defer to members of the pigmentocracy in a manner consistent with these broader patterns of inequality? These questions are assessed by matching white and black research participants with either a white, light-skinned black, or dark-skinned black partner for the completion of a joint task.
The results of the multi-site experiment suggest that there is racial invariance with the perceived status associated with members of the pigmentocracy. More generally, whites exhibit patterns of active denial and report that most others believe dark-skinned blacks are more competent than light-skinned blacks, who most others believe are more competent than whites. Whites purportedly personally subscribe to these pattern of beliefs. Blacks, however, exhibit a pattern of active resistance to stigmatizing beliefs: while they report that oppressed members of the pigmentocracy are held in lower regard by most others in society, they refuse to personally endorse these stigmatizing beliefs.
These attitudinal reactions had implications for the patterns of deference that emerged when jointly completing the group task. While patterns of influence emergent in group tasks generally reflect broader patterns of stratification in society, this failed to be the case when participants interacted with members of the pigmentocracy most phenotypically distinct from themselves. That is, when racial distinctions were most salient, research participants consciously reacted against the pigmentocracy, obstructing the activation of the status generalization process. The implications of these results for model testing and development, and for identifying racial biases in the current racial climate are discussed.
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Re-conceptualizing teacher expertise: teacher agency and expertise through a critical pedagogic frameworkSamoukovic, Biljana 01 December 2015 (has links)
Public and scholarly debates on what it means to be a successful teacher are characterized by increasingly pronounced differences in how various political, legislative, and professional groups define successful teaching. In response to pressures posed by these polarized discourses, critical pedagogic research on education contrasts contested views on the nature of knowledge and critiques the standardization of knowledge in schools. There is a general consensus in the research that it is necessary for teachers to develop an understanding of a rapidly changing world, and an understanding of students coming from various social milieus who are often unwilling to accept a uniform set of knowledge and values it promotes. Thus, the body of knowledge and the values which are supposed to be passed on to new generations of students continue to be points of contention in education. It is necessary for teachers to be aware of why certain sets of knowledge, skills, and values should be promoted in increasingly diverse school settings. In this expanded view of the teachers’ role and of teacher expertise, teacher agency, the nature of knowledge, sociopolitical relations, and power relations need to be considered.
In this dissertation I examine the interplay of these factors by examining the extant research and then analyzing the perceptions of a group of teacher participants in a qualitative study. I have synthesized the findings to develop a new concept of teacher agency expertise in a critical pedagogic sense. I clarify the relationship between teacher expertise and teacher agency. The concept of teacher expertise requires that teacher agency be conceived of in terms of its collective expressions and its larger influence, as well as the aim of effective teaching for equity and social justice.
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