• N-ethylmaleimide sensitive factor (NSF) is a regulator of plasma membrane rupture and necrotic cell death

      Elrod, John W.; Kishore, Raj; Tian, Ying; Soboloff, Jonathan; Calvert, John W. (Temple University. Libraries, 2021)
      Necrosis, originally considered chaotic, has been found to be regulated by distinct molecular pathways. To identify novel regulators of plasma membrane rupture, a hallmark of necrotic cell death, a genome-wide shRNA loss-of-function screen was performed. We identified SNARE complex members, mediators of canonical membrane fusion events, as necessary for Ca2+ and ROS-induced plasma membrane rupture andnecrosis. We targeted N-ethylmaleimide sensitive factor (NSF) due to its requirement in SNARE recycling, lack of gene homologs, and redox sensitivity. Deletion of Nsf protected against membrane rupture induced by various necrotic stimuli, yet did not influence apoptosis, suggesting specificity in programmed necrosis. We discovered that NSF localizes to sites of membrane blebbing and rupture. Additionally, SNARE-binding, ATPase activity, and redox modification are necessary for NSF’s role in necrosis. We generated conditional Nsf knockout mice and induced skeletal muscle injury via cardiotoxin injection. Loss of NSF protected against sarcolemmal rupture and myocyte death. Complementarily, cardiomyocyte-specific deletion of Nsf protected against ischemia-reperfusion injury. The SNARE complex regulator, NSF, is a key mediator of membrane rupture in necrotic cell death and a promising therapeutic target for numerous diseases.
    • N-METHYL-D-ASPARTIC ACID RECEPTOR SUBUNIT NR2A REPEAT

      Brown, Michael D.; Tierney, Ryan T.; Krynetskiy, Evgeny; Covassin, Tracey; Moffit, Dani M.; Mansell, Jamie (Temple University. Libraries, 2013)
      During a concussion, mechanical forces cause neuron cell strain that initiates dysfunction through the indiscriminate movement of ions through protein channels. Extracellular glutamate binds with cell membrane proteins (e.g. NR2A), which exacerbates the Ca2+ ion influx and prolongs neuron dysfunction. Genetic variation may be a factor in regulating glutamate binding and therefore cell recovery time. The NR2A subunit of NMDA contains a variable (GT)n nucleotide tandem repeat (VNTR) within GRIN2A promoter region. This VNTR has been shown to regulate transcription levels in a length dependent manner, where longer repeat decreases transcription of the NR2A subunit. The purpose of this study was to determine the association of the GRIN2A VNTR and recovery (days) as well as concussion severity scores within concussed athletes. The independent variable was VNTR (long allele vs. short allele). The primary dependent variable, recovery time, was defined as injury date to return to play (RTP) clearance date as determined by the physician. Participant RTP time was categorized as normal ( 20 days). Secondary dependent variables were assessed at the initial evaluation and included vestibular ocular score, Balance Error Scoring System (BESS) score, and Immediate Post Concussion and Cognitive Testing (ImPACT) module scores. All 51 participants were athletes, comprised of 38 males and 13 females with a mean age of 18.69  6.65. Participants were evaluated at a university concussion center. The standardized concussion evaluation consisted of cranial nerve, vestibular ocular tests, balance (Balance Error Scoring System), signs and symptoms (s/s), and neurocognitive (ImPACT) testing. Each participant was genotyped via saliva sample for the GRIN2A (GT)n repeat polymorphism (rs3219790). Data analysis consisted of descriptive and inferential statistics. Chi-squares were used to assess the association between VNTR (long allele versus short allele) and concussion recovery (prolonged versus normal). Regression analyses were used to estimate extent to which non-genetic factors and genotype contributed to concussion recovery group assignment. One-way ANOVAs were used to identify any significant differences in vestibular ocular, BESS, and ImPACT module scores between long and short alleles. Primary potential non-genetic contributing factors were age, race, sex, concussion history, dizziness at time of injury, history of migraines, and history of ADHD. The alpha level was set at p ≤ .05. There were no differences between demographic or health history within the VNTR or recovery groups. There was a significant association (x2 = 4.01, p = 0.045) between the VNTR group (dominant model: LL versus SS + LS) and recovery, where the chance of prolonged recovery was 4.3 times greater for carriers of the homozygous long allele. There were no differences in concussion severity scores between VNTR group and concussion severity scores. This was the first study to investigate the association of the (GT)n VNTR within GRIN2A. We established a DNA collection, estimation, and genotyping protocol of the (GT)n VNTR for 96 samples and demonstrated accuracy of this genotyping method. Clinically, athletes carrying the long allele genotype may be predisposed to prolonged recovery following a concussive injury.
    • N-Player Statistical Nash Game Control: M-th Cost Cumulant Optimization

      Won, Chang-Hee, 1967-; Helferty, John J.; Hutapea, Parsaoran; Ferrese, Frank; Du, Xiaojiang (Temple University. Libraries, 2014)
      Game theory is the study of tactical interactions involving conflicts and cooperations among multiple decision makers called players with applications in diverse disciplines such as economics, biology, management, communication networks, electric power systems and control. This dissertation studies a statistical differential game problem where finite N players optimize their system performance by shaping the distribution of their cost function through cost cumulants. This research integrates game theory with statistical optimal control theory and considers a statistical Nash non-cooperative nonzero-sum game for a nonlinear dynamic system with nonquadratic cost functions. The objective of the statistical Nash game is to find the equilibrium solution where no player has the incentive to deviate once other players maintain their equilibrium strategy. The necessary condition for the existence of the Nash equilibrium solution is given for the m-th cumulant cost optimization using the Hamilton-Jacobi-Bellman (HJB) equations. In addition, the sufficient condition which is the verification theorem for the existence of Nash equilibrium solution is given for the m-th cumulant cost optimization using the Hamilton-Jacobi-Bellman (HJB) equations. However, solving the HJB equations even for relatively low dimensional game problem is not trivial, we propose to use neural network approximate method to find the solution of the HJB partial differential equations for the statistical game problem. Convergence proof of the neural network approximate method solution to exact solution is given. In addition, numerical examples are provided for the statistical game to demonstrate the applicability of the proposed theoretical developments.
    • Naming Movement: Nomenclature and Ways of Knowing Dance

      Meglin, Joellen A.; Kahlich, Luke C.; Nagatomo, Shigenori; Zohn, Steven David, 1966- (Temple University. Libraries, 2011)
      This study examines dance terminologies and documentation of Korean and French court dances, Jeongjae and Belle Dance, respectively. For Belle Dance, Raoul Feuillet's Chorégraphie (1700) and Pierre Rameau's Maître à Danser (1725) provide lists of movement terms, definitions of them, and instructions for how to enact them. For Jeongjae, Jeongjae mudo holgi, written in the nineteenth century, comprises diagrams and descriptions of dance movements. These sources have their own ways of converting dance movement into language, revealing the divergent perspectives toward body movement in each culture. Their divergent modes of documenting dance demonstrate the characteristic ways of expressing and constructing knowledge of body movement of their historical and cultural contexts. By comparing the terminologies and documentation that carry historically and culturally specific concepts, I explore underlying assumptions about what kinds of information are considered knowledge and preserved through articulation in words and graphic symbols. This study addresses the research question, what do dance terminologies and processes of documentation suggest about perspectives on dance movement in two distinct dance cultures. To articulate the differences, this study examines selected documents as a whole and dance terms in specific. The significance of characteristic features found in the textual analysis will be illuminated through an exploration of intertextual relationships between the dance texts and important sources of the period that focus on the body and how it is conceived in relation to the human being. This study suggests that, dance documents, which translate selected aspects of dance movement into words and graphic symbols, encapsulate historically and culturally specific ways of knowing dance movement. Intending to capture movement analytically and visually, Belle Dance treatises attempt to establish objective knowledge of dance. This mode of knowing corresponds to philosophical and practical milieus that constructed the theory of mind-body dualism, mathematical foundations of modern science, and reliance on sense perceptions. In contrast, Jeongjae documents take the performer's experience as the standard point of view, considering his or her inner experience as well as observable results of movement. Correspondingly, Korean traditional culture adhered to a holistic view of the body and promoted implicit expressions to describe body movements.
    • Nanoscale confinement and interfacial effects on the dynamics and glass transition/crystallinity of thin adsorbed films on silica nanoparticles.

      Wunder, Stephanie L.; Varnum, Susan A.; Strongin, Daniel R.; Ilies, Marc A. (Temple University. Libraries, 2011)
      The research investigated in this dissertation has focused on understanding the structure-property-function relationships of polymer nanocomposites. The properties of composite systems are dictated by the properties of their components, typically fillers in a polymer matrix. In nanocomposites, the polymer near an interface has significantly different properties compared with the bulk polymer, and the contribution of the adsorbed polymer to composite properties becomes increasingly important as the filler size decreases. Despite many reports of highly favorable properties, the behavior of polymer nanocomposites is not generally predictable, and thus requires a better understanding of the interfacial region. The ability to tailor the filler/matrix interaction and an understanding of the impact of the interface on macroscopic properties are keys in the design of nanocomposite properties. In this original work the surface of silica nanoparticles was tailored by: a) Changing the number of sites for polymer attachment by varying the surface silanols and, b) By varying the size/curvature of nanoparticles. The effect of surface tailoring on the dynamic properties after the adsorption of two model polymers, amorphous polymethyl methacrylate (PMMA) and semicrystalline polyethylene oxide (PEO) was observed. The interphase layer of polymers adsorbed to silica surfaces is affected by the surface silanol density as well as the relative size of the polymer compared with the size of the adsorbing substrate. The non-equilibrium adsorption of PMMA onto individual colloidal Stöber silica (SiO2) particles, where Rparticle (100nm) > RPMMA (~6.5nm) was compared with the adsorption onto fumed silica, where Rparticle (7nm) ~ RPMMA (6.5nm) < Aggregate (~1000nm), both as a function of silanol density [SiOH] and hydrophobility. In the former case, TEM images showed that the PMMA adsorbed onto individual nanoparticles, so that the number of PMMA chains/bead could be calculated, whereas in the latter case bridging of PMMA between aggregates occurred. The anchoring point densities were comparable to the silanol densities, suggesting that PMMA adsorbed as trains rather than loops. For hydrophilic SiO2, Tg increased with [SiOH], as more carbonyl groups hydrogen bonded to the silanols, and was independent of particle morphology. For methylated silica, (CH3)3-SiO2, the adsorption isotherms were identical for colloidal and fumed silica, but Tg was depressed for the former, and comparable to the bulk value for the latter. The increased Tg of PMMA adsorbed onto fumed (CH3)3-SiO2 was attributed to the larger loops formed by the bridging PMMA chains between the silica aggregates. For nanocomposites the interphase region becomes more important as the surface/volume ratio of the nanoparticles increases. Polymers have chain dimensions (characterized by the radius of gyration, Rg) similar to the nanoparticles (Rnanoparticle) themselves, so that chain conformation, mobility and crystallinity can be affected by Rg/Rnanoparticle. Here, both the glass transition temperature (Tg) and degree of crystallinity (Xc) of polyethylene oxide (PEO) on individual SiO2 nanoparticles of nominal 15, 50 and 100 nm diameter (2 RSiO2) , in which Rg (PEO) was greater, equal to or less than RSiO2 was investigated. Plateau adsorption of PEO on SiO2 nanoparticles (PEO-SiO2) increased in the order PEO-SiO2 (100 nm) > PEO-SiO2 (50 nm) > PEO-SiO2 (15 nm). At plateau adsorption after melting and solidification, the samples were completely amorphous. The Tg of the adsorbed PEO increased in the order PEO-SiO2 (100 nm) > PEO-SiO2 (50 nm) > PEO-SiO2 (15 nm); since the Tgs were above 25oC in all cases, the PEO behaved more like a brittle solid than an elastomer. For comparable amounts of PEO that were adsorbed from solution but not melted, the melt endotherm increased in the order PEO-SiO2 (15 nm) > PEO-SiO2 (50 nm) > PEO-SiO2 (100 nm). These trends were interpreted as due to an increase in loop/tail lengths and thus flexibility, with a concomitant ability to crystallize, as Rg (PEO)/RSiO2 decreased and which was the result of less hydrogen bond formation between the oxygens of PEO and the silanols (SiOH) of the SiO2 as the nanoparticle size decreased. This in turn was attributed to the energetically unfavorable conformations necessary for the PEO chains to adopt in order to hydrogen bond with silanols on the smaller nanoparticles. The degradation behavior of amorphous PMMA and semicrystalline PEO on silica (SiO2) nanoparticles as a function of silanol density and nanoparticle size was investigated by derivative thermogravimetric analysis (DTGA) for adsorption amounts below plateau adsorption. For PMMA Td decreased as the number of SiOH/C=O contacts decreased, either from heat treatment of the SiO2, which reduced the silanol density, or as the nanoparticle size decreased, reducing the numbers of places that the PMMA chain contacted the nanoparticles.
    • Narrative Identifications among Anarcho-Punks in Philadelphia

      Vila, Pablo, 1952-; Gordon, Lewis R. (Lewis Ricardo), 1962-; Zhao, Shanyang, 1957-; Wright, Thomas (Temple University. Libraries, 2012)
      This dissertation uses in depth interviews and participant observation in order to understand an important contemporary subculture: anarcho-punks. The research was done in Philadelphia, Pennsylvania between the years of 2006 and 2012. The overarching theme that connects the different chapters of the dissertation together is a focus on the ways in which the identification narratives of participants are ethical in nature, meaning that the narrators are working to maintain an ethical sense of self in their narration. In addition, I show the identitarian consequences of the ways in which the hyphenation of the anarcho-punk identification works to both separate and join the two different identifications "anarchist" and "punk." I also show the ways in which identifications are narratively structured. This is done throughout the ten chapters of the dissertation. Each of the substantive chapters focuses on the different narratives used by the participants to understand a particular theme that is important to developing an understanding of the subculture overall.
    • Naskh al-Qur'an: A Theological and Juridical Reconsideration of the Theory of Abrogation and Its Impact on Qur'anic Exegesis

      Blankinship, Khalid Yahya; Ayoub, Mahmoud; Wright, Robert B.; Hasan, Zameer U. (Temple University. Libraries, 2011)
      The Qur'an has always been a medium through and upon which Islam and the Muslim faith are structured and built. It mediates the relationship between Muslims and God. Despite its alleged divine origin, the Qur'an as a scriptural and textual reality remains to be understood by Muslims. Many theories and principles have been developed out of the long Qur'anic interpretive tradition to address the Muslims' theological and legal needs. One of the most interesting, yet controversial, exegetical legal theories is the theory of naskh, a theory stipulating the abrogation of a verse of the Qur'an by another. The discourse of naskh raises many unsettling theological and legal questions. The present proposed research attempts to reassess the early Muslim understanding of the theory of Qur'anic abrogation. It raises fundamental questions about the accuracy of the assumptions of the early Muslim conception of textual annulment and the ongoing legal discourse of Islamic law in Muslim scholarship. It is the thesis of this proposed study that the theory of abrogation has been historically and traditionally conceived and discussed in a very rigid and dogmatic fashion as a result of the theological misconception of the immutability of both the divine will and revelation, and that the theory of naskh, as such, has failed to appropriate the legal contents of the law within the structures of juridical discourse. In other words, the rigidity and dogmatic nature of the theory of naskh has rendered the theory an inadequate conceptual framework to deal with an ever changing legal need of our time. Muslims to this day have struggled to preserve, adapt and redefine their social and legal norms in the face of changing situations. A central issue in this ongoing struggle has been the question of the nature, status, authority, and viability of the Qur'an and the Islamic law. The intellectual tradition of Islam has provided the underpinnings for adaptation, reform, and evolution. It is within this tradition of Islamic intellectualism that this proposed research intends to contribute. The theological component of this research will influence the way revelation is understood in Islam, while the legal component hopes to initiate a new Muslim attitude towards Islamic law. The exegetical consideration will hopefully create a reorientation of hermeneutical principle in Qur'anic exegesis. This study of naskh, for all its intent and purpose as outlined above, is primarily a study of naskh al-Qur'an as captured by the formative sources of `Sunni' Islam. It is therefore the case that this study should be strictly understood as one that does not pretend to include nor represent the views of Shi`ism on naskh in the Qur'an or the theory of naskh in itself.
    • National Narratives and Global Politics: Immigrant and Second-Generation Iranians in the United States and Germany

      Byng, Michelle; Grasmuck, Sherri; Espinal, Rosario (Temple University. Libraries, 2014)
      This dissertation project examines the lived experiences of immigrant and second- generation Iranian immigrants to uncover the factors that shape their perceptions of belonging in two differ western nations. It is a qualitative methods study that utilized in-depth interviews. I address the limitations of past research by highlighting that Iranians' experiences of belonging and membership in western nations are greatly influenced by the national narratives of their host societies and the global politics surrounding Iran. My central research questions are: How do America's and Germany's national narratives of immigration influence Iranians' sense of belonging? and How do Iranians perceive the global politics surrounding Iran as impacting their lives in the West? Research on Iranians in the United States and Europe underscores Iranians' proclivity to become entrepreneurs in their new nation, the lack of solidarity and community among Iranians, and the discrimination that they experience due to their ethnic and religious identities. However, we lack comparative scholarship that examines Iranian immigrants' experiences in two nations where the national narratives are different. Moreover, there is an absence of research that addresses whether, and how, global politics influence perceptions of belonging. The three empirical chapters examine the data from sixty-four in-depth interviews with immigrant and second-generation Iranians living in northern and southern California, and Hamburg, Germany. In the first interview data chapter, I examine the motivations of Iranians' migration to the US and Germany, their settlement experiences, and their expectations of their lives in their new nation. Specifically in this chapter, I reveal that the lack of foreign policy considerations for post-Revolution Iranian exiles in the US and the institutionalized nature of refugee policy, and lack of it, in each nation helps explain the varying settlement experiences of immigrant-generation Iranians in the US and Germany. It is noteworthy that these experiences also helped shape Iranians' understanding of each nation's main values and characteristics. In the second empirical chapter, I show that national narratives of immigration are important in shaping Iranian immigrants' understandings, expectations, and experiences of belonging and membership in the US and Germany. These narratives inform their interpretations of not just the prospects of belonging, but the indications of whether they have accomplished it. In the last data chapter, I explore how Iran's global political standing influences the lives of Iranian immigrants living in the US and Germany. In both the US and Germany, the dominant negative discourse surrounding a highly politicized homeland stigmatizes Iranians' identities, and makes them more subject to experiences of marginality and discrimination. Specifically, in the US, global politics puts a cap on Iranians' quality of middle class experiences, and facilitates the construction of social marginality and discrimination against them. In Germany, it helps solidify a boundary that is already there. Ultimately, this dissertation research uncovers three important aspects in regards to perceptions of belonging among Iranians in the US and Germany: First, a comparison of Iranian immigrant experiences in two western nations where the narratives of belonging are considerably different demonstrated that the national narratives of an immigrants' host society greatly shape and mediate perceptions and experiences of belonging and membership. Specifically in the US, Iranians perceive belonging when they can obtain opportunities for social mobility, when their ancestry is not marked or stigmatized, and when they can place themselves in the `nation of immigrants' narrative. In Germany, Iranians perceive that they can come close to belonging once they are perceived as having culturally accommodated to German society, can access greater opportunity structures, and are perceived and accepted as `good foreigners and immigrants'. Second, an examination of how global politics surrounding Iran impact Iranians' lives in western nations revealed that their identities are stigmatized; they encounter marginality and exclusion, and ultimately feel that they do not belong or have full membership in the US and Germany. Interestingly, Iranians in both nations hypothesized that an improved Iranian standing would help facilitate belonging and membership. What is more, their perceptions of how their lives would change, and how belonging would take shape, if they did not live with the stigmas created by Iran's global politics, were inextricably linked to the national narratives of their host societies. Third, there were significant generational differences in how the second-generation in each nation assessed belonging. In the US, the second-generations' ability to access the educational resources needed for professional careers, despite their perceptions of the existence of anti-Iranian prejudice, legitimized both the US national narrative and proved to them that they can secure a good quality of life and be a part of US society. In Germany, the second generation experienced generational lag with regard to belonging. Their ability to belong is not resolved by length of residence, German citizenship, German educational attainments, or their adherence German cultural norms and practices. Rather, second generation believed that being marked as foreigners was perpetual, and not an identity that one loses after a few generations. Ultimately, among the US second-generation US sample there were more significant/powerful declarations of the ability to acquire social mobility and belonging, while those in Germany experienced a more generalized feeling of not belonging. This research contributes to ongoing conversations regarding immigrant belonging and membership. It adds the comparative dimension of belonging and membership by examining evaluations of belonging in two western nations where the national narratives are different. Furthermore, it takes into account how the contentious and antagonistic political relationship between Iran and western nations has impacted Iranians' lived experiences, and ability to belong, in the US and Germany. Ultimately, the inclusion of national narratives and global politics contributes to our understanding of the sociological processes that facilitate, and disrupt, experiences of immigrant belonging and membership in their host society, and provides us with a deeper understanding of the layered and complex dynamics that shape immigrant experiences.
    • NATO's Crisis Years: The End of the Atlantic Mystique and the Making of Pax Atlantica, 1955-1968

      Immerman, Richard H.; Hitchcock, William I.; Zubok, V. M. (Vladislav Martinovich); Lockenour, Jay, 1966-; Kaplan, Lawrence S. (Temple University. Libraries, 2014)
      What is NATO? This diplomatic history reveals that NATO and its meaning were contingent and never static. Instead, NATO was a machine the allies sought to adapt and use to achieve their national interests. NATO was shrouded in an "Atlantic mystique," the suggestion that the allies practiced a unique and exceptional type of cooperation based on shared values and common heritage. But this mystique did not define or ensure NATO's longevity; in fact NATO was thought necessary because of differences between the allies. The allies' national interests did converge on fundamental points, like the need for security. But they rarely agreed on specifics. And when they disagreed on basic questions, like NATO's relationship to the rest of the world, the role of Europe in NATO, and the American commitment to the continent, sparks flew. But because NATO was not static, it could adapt. And the hope held by each ally that they could convince their allies to change NATO to meet their needs - the hope inherent in a dynamic NATO machine - kept the allies working together. From 1955 to 1968, both the allies and the world situation changed dramatically. So to did the allies' plans and uses they saw for NATO. The primary interest of allies was protection from the Soviet Union. But the allies - even some in the Federal Republic of Germany - also believed NATO protected them from a resurgent Germany. Just how to defend against either threat was never agreed. But the allies believed that NATO, by keeping the Cold War cold, and by fostering cooperation between the western European states, established a Pax Atlantica. In this Atlantic peace the allies prospered. They cooperated and they competed, but peacefully. By the end of the 1960s, the allies believed NATO was necessary to maintaining the Pax Atlantica, even if - especially if - the Soviet empire collapsed. Amidst the crises of the 1950s and 1960s, the allies came to believe NATO was guaranteed a long future.
    • Natural Play, Healthy Play: Environmental Determinants of Young Children's Outdoor Physical Activity

      Sachs, Michael L.; Hineline, Philip Neil; Butcher-Poffley, Lois A.; DuCette, Joseph P. (Temple University. Libraries, 2015)
      The prevalence of obesity among young children has markedly increased over the past two decades, with more than one-third of American preschoolers now overweight or obese and at risk for lifelong health problems. Physical activity is a recommended obesity prevention strategy, yet preschoolers typically fail to meet recommended daily physical activity guidelines, spending just 15 minutes engaged in moderate to vigorous physical activity, compared to six sedentary hours daily. Unstructured play in settings with varied features, such as childcare center playgrounds, potentially plays a significant role in increasing the amount of time preschoolers spend in moderate-to-vigorous physical activity (MVPA). The purposes of this study were first, to compare the intensity and type of preschoolers' physical activity across four distinctly different outdoor play settings; second, to identify particular features in each play setting associated with MVPA and sedentary behavior; and, third, to identify, test, and evaluate environmental modifications to increase preschoolers' MVPA in outdoor play settings. Seventeen 3-5 year-old children participated in repeated unstructured play sessions featuring 16 min of play in each of 4 novel settings: a traditional climber, a wooded natural area, a garden, and an adventure, or "loose parts" playground. Interventions to increase physical activity were introduced to the adventure playground during the first two phases, and to all four settings during the third phase. Physical activity intensity was measured using ActiGraph GT3x+ activity monitors and contextual information concerning motor skills was obtained by trained observers using the System for Observing Play and Recreation in Communities (SOPARC), adapted to the age and environment of the study. Results show that both play setting design theme and the composition of specific play features within the setting impact the type of motor skills children perform and the amount of MVPA young children accumulate during unstructured play. Findings additionally demonstrate that simple, low-cost modifications to play settings can increase MVPA for targeted subgroups and individual children; outcomes were setting-specific. Study results may be useful to public health and medical workers, parents, educators, playground designers, community planners, and policy makers who focus on increasing preschool children's daily MVPA and decreasing childhood obesity.
    • NATURAL PRODUCT ANALOGUES AND 2-PYRIDONE PHOTOCHEMISTRY

      Sieburth, Scott McNeill; Andrade, Rodrigo B.; Wang, Rongsheng; Cannon, Kevin C. (Temple University. Libraries, 2020)
      There is a profound need for new antibiotics which overcome bacterial resistance. The predominant source for these is natural products; however, they are often quickly rendered ineffective due to antibiotic resistance. A proven method in drug discovery is improving the properties of natural products through diverted total synthesis (DTS). Of particular interest is promysalin, which is produced by Pseudomonas putida, and selectively inhibits the growth of Gram-negative pathogenic bacteria Pseudomonas aeruginosa at nanomolar concentrations. The work herein describes modifications to the side chain which were shown to modulate antibacterial potency and specificity. A similarly inspired approach to countering antibiotic resistance is the targeted modification of a single carbon to silicon, motivated by the proven success of this substitution shown in pharmaceuticals and amino acids. The target for this modification is albocycline, a known macrolactone antibiotic that exhibits potent antibiotic activity against S. aureus. Replacing the C4 carbon of albocycline with silicon will provide sila-albocycline with enhanced hydrogen bonding properties and altered lipophilicity due to the slight changes from the carbon to silicon atom. In addition, there is anticipated intrinsic stability of the silanol toward rearrangement reactions than carbon-based. The proposed synthesis diverts from the known total synthesis of albocycline, as reported by the Andrade Group. This work details the efforts made towards the total synthesis of sila-albocycline. Lastly, there is untapped potential for UV-promoted photochemistry to create molecular scaffolds, which may lead to novel synthetic routes to complex molecules in addition to providing new polycycles that may expand current medicinal products. The work herein describes the synthesis of tethered chloro- and methoxy-substituted benzyl alcohols to 2-pyridones and the resulting products when exposing the solution to ultraviolet light. This generated new polycycles with complex structures which have unexplored biological or medicinal properties.
    • NATURAL PRODUCT AND BUILDING BLOCK SYNTHESIS: CAROLACTON-INSPIRED ANALOGS, THE ANTITUMOR THERAPEUTIC FRAX-1036, AND THE CONSTRUCTION OF ATOMICALLY PRECISE MEMBRANES FROM SPIROLIGOMERS

      Schafmeister, Christian; Wang, Rongsheng; Sieburth, Scott McNeill; Cannon, Kevin C. (Temple University. Libraries, 2019)
      Ever since traditional medicine developed thousands of years ago, humans have looked to natural substances as remedies for maladies. Today, many isolation and natural product chemists have begun revisiting ancient folk medicines in an attempt to isolate the compound(s) responsible for effective treatment. In addition to the examination of traditional remedies, the secondary metabolites of many newly discovered species, especially bacteria, get tested against a wide array of pathogenic cells. Isolated from the myxobacterium Sorangium cellulosum, the secondary metabolite carolacton was discovered to be lethal to Streptococcus mutans cells transitioning to the biofilm state. This was a significant finding since S. mutans is the main causative agent of dental caries, the most prevalent chronic childhood and adolescent disease worldwide. Herein, our efforts to design, synthesize, and biologically evaluate a 16-member library of carolacton-inspired analogs is described. In addition to natural product inspired research, two projects borne from a target-oriented templated approach are also described. The first, the synthesis of the antitumor compound FRAX-1036, was completed as part of a collaboration with the Chernoff group at Fox Chase Cancer Center to provide them with more material for murine testing. The second, the synthesis of macrocycles for the formation of atomically precise membranes, was conducted using spiroligomer building blocks and unnatural amino acids to furnish a triangle-shaped macrocycle via solution and solid phase techniques. This dissertation highlights the usefulness of the techniques of diverted total synthesis and building block synthesis in organic chemistry.
    • Natural Resource Use in Madagascar

      Sewall, Brent J.; Sanders, Robert W.; Cordes, Erik E.; Tanaka, Jacqueline; Pearsall, Charlyn (Temple University. Libraries, 2015)
      The anthropogenic use of natural resources has become a major cause of biodiversity loss and habitat degradation throughout the world. Deforestation - the conversion of forests to alternative land covers - has led to a decrease in local biodiversity directly through a decrease in habitat, and indirectly through habitat fragmentation. Likewise, defaunation – the loss of animals both directly through hunting and indirectly through deforestation – has led to the empty forest syndrome and subsequent deterioration of forest ecosystems. In many cases, areas where anthropogenic use of natural resources is high overlap with areas of high biodiversity value. Therefore, the present series of studies aims to better understand the impacts that different types of natural resources use and habitat degradation have on biodiversity. This dissertation details the results of five studies, which aimed to: 1) examine the effects of habitat degradation on plant-frugivore networks; 2), understand the live capture and extent of ownership of lemurs in Madagascar; 3) understand the micro- and macro-level drivers of wild meat consumption in Madagascar; 4) describe the capture, movement, and trade of wild meat in Madagascar; and 5) the impacts of habitat changes on the diets and vertical stratification of frugivorous bats. For the first study, our objectives were to understand the effects of habitat degradation on (1) community structure, (2) network structure, and (3) seed dispersal services. We focused on fruit-bearing trees and frugivores (two lemur and five bird species) across a three-point gradient of habitat degradation in a tropical dry forest in Madagascar. Our objectives were to understand the effects of habitat degradation on (1) community structure, (2) network structure, and (3) seed dispersal services. We focused on fruit-bearing trees and frugivores (two lemur and five bird species) across a three-point gradient of habitat degradation in a tropical dry forest in Madagascar. Data on fruit consumption by frugivores were collected over 592 hours of observations at 13 fruiting tree species. We found that as habitat became more degraded: (1) the community structure of both frugivores and fruiting tree communities changed; (2) the mutualistic network structure became less complex and less connected; (3) the interaction strengths of pair-wise interactions changed and the asymmetries of these interactions shifted; and (4) seed dispersal decreased by 91% in the secondary forest, compared to the primary forest. In addition, we show that frugivores: (1) sometimes stopped eating fruit in the degraded forest, even when they had consumed it in other forests; and (2) appeared to avoid some fruiting tree species while showing preference for others. The mutualistic network studied in this paper appeared sensitive to anthropogenic disturbance and a novel measure of effectiveness helped quantify these changes. For the second study, our objectives were to provide the first quantitative estimates of the prevalence, spatial extent, correlates and timing of lemur ownership, procurement methods, within-country movements, and numbers and duration of ownership. Using semi-structured interviews of 1,093 households and 61 transporters, across 17 study sites, we found that lemur ownership was widespread and affected a variety of taxa. We estimate that 28,253 lemurs have been affected since 2010. Most lemurs were caught by owners and kept for either short (≤1 week) or long (≥3 years) periods. The live capture of lemurs in Madagascar is not highly organized but may threaten several endangered species. For the third study, we investigated the role of wild meat in food security in Madagascar, a country where wild meat consumption is poorly understood in urban areas and at regional scales. Using semi-structured interviews (n = 1339 heads-of-households, 21 towns), we aimed to: 1) quantify the amount and purpose of; 2) understand the drivers behind; and, 3) examine recent changes in wild meat consumption in Madagascar. Few respondents preferred wild meat (8 ± 3%) but most had eaten it at least once (78 ± 7%), and consumption occurred across ethnic groups, in urban and rural settings. More food insecure areas reported higher rates of recent consumption of wild meat. However, consumption was best explained by individual preferences and taboos. Few respondents (<1 ± <1%) had increased rates of consumption during their lifetimes, and wild meat prices showed no change from 2005-2013. Most consumption involved wild pigs and small-bodied animals, though these animal groups and lemurs were consumed less in recent years. Given these data, wild meat is unlikely to enhance food security for most Malagasy people in urban and well-connected rural areas. For the fourth study, and to improve understanding of the wild meat trade in Madagascar, our objectives were to: (1) quantify the volume of consumption, transport, and sale for different animal groups, compared to domestic meat; (2) describe the methods of capture and hunting for different animal groups; (3) analyze the patterns of movement of wild meat from the capture location to the final consumer, compared to domestic meat; and (4) examine how the prices of wild meat change depending on the venue through which the consumer purchases it. Data was collected in May-August 2013 using semi-structured interviews of consumers (n = 1343 households, 21 towns), meatsellers (n = 520 restaurants, open-air markets stalls, and supermarkets, 9 towns), and drivers of inter-city transit vehicles (n = 61, 5 towns). We found that: (1) a wide range of hunting methods were used, though their prevalence of use differed by animal group; (2) wild meat traveled distances of up to 166 km to reach consumers, though some animal groups were hunted locally (<10 km) in rural areas; (3) most wild meat was procured from free sources (hunting and receiving meat as a gift), though urban respondents who consumed bats and wild pigs were more likely to purchase those meats; and (4) wild meat was consumed at lower rates than domestic meat, though urban respondents consumed twice as much wild meat as rural respondents. We conclude that urban and rural respondents differ in how they interact with the wild meat commodity chain. We also believe that the consumption and trade of wild meat in Madagascar is likely more formalized that previously thought. Finally, for our fifth study, we used stable isotope analysis to examine how foraging by three fruit bat species in Madagascar, Pteropus rufus, Eidolon dupreanum, and Rousettus madagascariensis, are impacted by habitat change across a large spatial scale. Our results indicated that the three species had broadly overlapping diets. Differences in diet were nonetheless detectable and consistent between P. rufus and E. dupreanum, and these diets shifted when they co-occurred, suggesting resource partitioning across habitats and vertical strata within the canopy to avoid competition. Changes in diet were also correlated with a decrease in forest cover, though at a larger spatial scale in P. rufus than in E. dupreanum. These results suggest fruit bat species exhibit differing foraging strategies in response to habitat change. They also highlight the key threats that fruit bats face from habitat change, and clarify the spatial scales at which conservation efforts should be implemented to mitigate threats for these bat species in Madagascar.
    • NATURE OF AND RISK FOR EXPERIENCING MIXED STATES IN RECENT-ONSET BIPOLAR SPECTRUM SAMPLE

      Alloy, Lauren B.; Drabick, Deborah A.; McCloskey, Michael S.; Olino, Thomas; Chen, Eunice Y.; Weisberg, Robert W. (Temple University. Libraries, 2015)
      Clinicians and researchers have identified a pattern of "mixed" symptoms that are sometimes exhibited by individuals with bipolar spectrum disorders (BSDs). However, the criteria for these mixed states as outlined by the American Psychological Association have been criticized for being too stringent for most individuals that experience impairing episodes of mixed symptomatology (e.g., Akiskal, 1996). Mixed states are associated with a more impairing course of illness and suicidality. More research is needed on mixed states, and there is particularly little evidence for risk factors in recent-onset samples. The aims of this study were to 1) examine the prevalence of mixed states in a sample of individuals with recent-onset bipolar spectrum disorders, 2) examine the symptom structure of hypomanic and depressive episodes, and 3) examine some of the risk factors associated with mixed states. Participants in sample 1 were adolescents, initially aged 14-19, selected for exhibiting either moderate or high Behavioral Approach System (BAS) risk for first onset of BSDs. Participants in sample 2 were 18-24 year old undergraduates from Temple University recruited for having a bipolar spectrum diagnosis. Mixed states captured 37.10% of all episodes examined in sample 1, yet only 13 (10.48%) of these episodes met available research criteria for mixed mood episodes. Factor analysis yielded two adequate models that fit the data; one model had two factors that aligned with traditional depressive and hypomanic symptomatology, and another model had three factors that aligned with hypothesized overactivity, inhibited depression, and irritable risk taking components of bipolar disorder. Latent class analysis allowed for examining observed patterns of responses within individuals, and then grouping heterogeneous groups of individuals into classes based on similarities on dimensions of interest, performance within dimensions, or both (Nylund, Bellmore, Nishina, & Graham, 2007). The latent class analysis showed that three classes best defined bipolar spectrum individuals in sample 1: low impulsivity, aggressive, and substance problems classes were obtained. The `aggressive' class was significantly more likely than the `low impulsivity' class to experience any mixed symptomatology, although a continuous measure of mixed symptoms did not yield significant differences between classes. Overall, the results from the current study support findings suggesting that mixed mood states are more commonly experienced than originally believed. These results extend previous studies to include individuals with bipolar spectrum disorders, not solely bipolar I and II disorders. These findings also suggest that non-treatment-seeking samples may have different types of mixed mood states than those seeking treatment. These findings add support to the literature that individuals with BSDs and comorbid substance use diagnoses are at increased risk for chronic illness, and show that these individuals are also more likely to experience mixed mood states than those without comorbid substance use diagnosis. Treatment providers should be aware of the complications that are inherent in bipolar individuals with comorbid substance diagnoses, as they are more likely to experience more episodes as well as mixed symptoms.
    • Navigating Neighborhoods: How Social Networks and Space Shape the Decisions and Experiences of Families in Housing Mobility Programs

      Goyette, Kimberly A.; Shlay, Anne B.; Elesh, David; Edin, Kathryn, 1962- (Temple University. Libraries, 2011)
      This dissertation analyzes the ways that race, class, and gender intersect in specific spatial contexts to shape access to opportunity and influence families' neighborhood decisions and experiences. I add to existing research by examining the initial processes of adjusting to new neighborhoods, focusing especially on the components of neighborhood transitions that are significant for low-income women and their children. I use in-depth qualitative interview data that was collected by Northwestern University's Institute for Policy Research between 2002 and 2005 with a randomly chosen sample of adults and youth in 91 families who participated in the Gautreaux Two housing mobility program in Chicago. This analysis assesses the various factors that influenced the range of program outcomes in order to understand the social processes involved. The results of this analysis show that respondents had complicated perspectives about moving out of public housing. Most respondents were eager to move out of their baseline neighborhoods, especially for the sake of their children. However, many also cited things they missed about the neighborhood once they moved. Many faced severe obstacles in locating an eligible unit. Some of these obstacles related to the poor implementation of the Gautreaux Two program, as well as to the tight rental market in Chicago at the time. After moving through the program, many families experienced hassles with landlords, substandard unit quality, distance from kin and support networks, and difficulty in creating new social ties in placement neighborhoods resulting in social isolation and transportation and financial difficulties. Other respondents had supportive relationships with landlords, good quality units, were able to maintain ties with kin, and developed relationships with new neighbors. Participants generally valued the racial diversity of their Gautreaux neighborhoods, and many emphasized the importance of having their children live in racially diverse areas. While some respondents' children faced discrimination in their new neighborhoods and schools, this was not the primary impetus for making subsequent mobility decisions. Policy implications include the need for further pre-move housing counseling for families in mobility programs, as well as continued program assistance to build and maintain strong social networks and connections to resources.
    • NAVIGATING PATERNAL HURDLES: A STRENGTHS-BASED EXPLORATION OF THE WAYS YOUNG BLACK MEN CONSTRUCT AND ENACT FATHERHOOD IN SOUTHWEST PHILADELPHIA

      Wood, Jennifer, 1971-; Payne, Yasser Arafat; Fader, Jamie J.; Fagan, Jay (Temple University. Libraries, 2020)
      The literature on desistance and crime-prevention finds that paternal engagement is correlated with increased self-esteem, and decreased delinquency, criminality and recidivism for both fathers and children (Holmes et al., 2012; James, 2015; Makariev & Shaker, 2010; Martinez, DeGarmo, & Eddy, 2004; Visher et al., 2011). While there is a breadth of research examining the collateral consequences of justice-involvement, such as employer discrimination and housing insecurity, there remains a dearth of literature exploring how these consequences specifically impact fathering. Because paternal engagement has implications for public safety, it is imperative to identify the personal and environmental factors that facilitate or challenge paternal engagement and the ways that paternal identity construction influences how fathers engage with their children. The current study employs a strengths-based perspective that acknowledges broader contextual forces that can impact marginalized fathers and explores the process of paternal identity construction and enactment within a novel framework that integrates perspectives from bioecological theory and identity theory. In particular, it investigates the ways young Black fathers navigate and adapt to different barriers to fathering, with a specific focus on police encounters and hypersurveillance. The research design comprises a qualitative approach that begins with a narrative inquiry interview followed by a subsequent interview that expands on themes discovered during the narrative inquiry. The study draws from interviews with 50 Black fathers between the ages of 25-34, with at least one biological child, living in the 19143 zip code of Philadelphia. Guided by the Dynamic Identity Construction and Enactment (DICE) model, the current study finds that social interactions with family, community, and criminal justice agents; internalized images of fathers and police in the media; and historical phenomena, such as mass incarceration and the crack epidemic cumulatively impact both paternal identity construction and fathering behavior for young Black men living in Southwest Philadelphia. This study suggests the use of the DICE model in research with marginalized communities, as it engenders a strengths-based lens by exploring both individual and contextual influences on individuals and communities. Findings also suggest (a) a reframing of deviance, (b) the use of person-first language in order to lessen the stigma of a criminal record (i.e. using terms such as “incarcerated individuals” instead of “inmates”), (c) increased non-law related interactions between police and community members in order to enhance familiarity and assuage fear on both ends, (d) a shift towards community corrections in order for fathers to remain active in their children’s lives, and (e) a greater focus on community-based coparenting programs in order to ensure that fathers maintain access to their children.
    • NAVIGATING THE BUILT ENVIRONMENT: READING BERENICE ABBOTT’S CHANGING NEW YORK

      Silk, Gerald; Orvell, Miles; Orvell, Miles (Temple University. Libraries, 2016)
      My thesis seeks to broaden the framework of conversation surrounding Berenice Abbott’s Changing New York. Much scholarship regarding Changing New York has focused on the individual photographs, examined and analyzed as independent of the meticulously arranged whole. My thesis considers the complete photo book, and how the curated pages work together to create a sort of guide of the city. Also, it has been continually noted that Abbott was a member of many artistic circles in New York City in the early 1930s, but little has been written analyzing how these relationships affected her artistic eye. Building on the scholarship of art historian Terri Weissman, my thesis contextualizes Abbott’s working environment to demonstrate how Abbott’s particular adherence to documentary photography allowed her to transcribe the urban metamorphosis. Turning to the scholarship of Peter Barr, I expand on his ideas regarding Abbott’s artistic relationship to the architectural and urban planning theories of Lewis Mumford and Henry-Russell Hitchcock. Abbott appropriated both Mumford and Hitchcock’s theories on the linear trajectory of architecture, selecting and composing her imagery to fashion for the viewer a decipherable sense of the built city. Within my thesis I sought to link contemporary ideas of the after-image proposed by Juan Ramon Resina to Abbott’s chronicling project. By using this framework I hope to show how Abbott’s photographs are still relevant to understanding the ever-changing New York City.
    • Near Infrared (NIR) Spectroscopic Assessment of Engineered Cartilage

      Pleshko, Nancy; Patil, Chetan Appasaheb; Bellas, Evangelia; Burdick, Jason A. (Temple University. Libraries, 2017)
      Articular cartilage has limited intrinsic healing capacity due to its dense and avascular structure. Clinical approaches have been developed to address the limitations associated with the poor ability of articular cartilage to regenerate. Current clinically approved techniques, however, can result in repair tissue that lacks appropriate hyaline cartilage biochemical and biomechanical properties, which lead to uncertain long-term clinical outcomes. Using tissue engineering strategies and a range of scaffolding materials, cell types, growth factors, culture conditions, and culture times, engineered tissues have been produced with compositional and biomechanical properties that approximate that of native tissue. In these studies, a considerable number of samples are typically sacrificed to evaluate compositional and mechanical properties, such as the amount of deposited collagen and sulfated glycosaminoglycan (sGAG) in the constructs. The number of sacrificed samples, as well as the amount of time and resources spent to evaluate the sacrificed samples using current gold standards, motivates an alternative method for evaluation of compositional properties. Vibrational spectroscopy, including infrared, has been considered as an alternative technique for assessment of tissues over the last 15-20 years. Infrared spectroscopy is based on absorbance of infrared light by tissue functional groups at specific vibrational frequencies, and thus, no external contrast is required. Vibrational spectroscopy is typically performed in two frequency regions, the mid infrared region (750-4000 cm-1), where penetration depth is limited to approximately 10 microns, and the near infrared (NIR) region (4000-12000 cm-1). In the NIR region, penetration of light is on the order of millimeters or centimeters, which makes it ideal for obtaining data through the full depth of engineered constructs. Here we employ NIR spectroscopy to nondestructively monitor the development of tissue-engineered constructs over culture period.
    • NEAR INFRARED SPECTROSCOPIC ASSESSMENT OF BONE WATER BINDING TO COLLAGEN AND MINERAL

      Pleshko, Nancy; Pleshko, Nancy; Patil, Chetan Appasaheb; Barbe, Mary F.; Tumarkin-Deratzian, Allison; Rajapakse, Chamith (Temple University. Libraries, 2019)
      Cortical bone fragility increases with age, therapeutic drug use and disease states. Clinically, bone fragility is evaluated by assessment of bone mineral density (BMD); however, studies have shown that other factors such as bone architecture, cell turnover and tissue composition influence bone quality. There is growing evidence that age related changes in bone water associated with collagen and/or mineral have a direct impact on bone mechanical competence and structural integrity. Understanding these compositional changes will aid in improved diagnose and prediction of fractures. Magnetic resonance imaging (MRI) is used to evaluate bone water, but this modality is limited in spatial resolution and is still being developed. Although still in the experimental stage, vibrational spectroscopy in the near infrared region (NIR) also known as near infrared spectroscopy (NIRS) is a nondestructive modality that can spatially evaluate alterations of bone composition. NIRS is a unique nondestructive technique that produces a signature spectrum by penetrating high frequency (4000-12,000 cm-1) non-ionizing radiation into material. NIRS permits a depth of penetration from millimeters to centimeters, dependent on frequency (wavelength). NIRS is very sensitive to water and can be used to provide molecular information of water related to collagen and mineral in bone samples. To date, definitive information on which NIR absorbances are linked to collagen or mineral bound water have not been identified. The overarching hypothesis is that water associated with collagen and/or mineral can be identified using NIRS and will serve as a biomarker for bone fragility in future preclinical studies. This will be achieved with the following three aims: First, to develop a method to image human cortical bone tissue using NIRS; second, to identify NIRS absorbances of water bound with mineral and collagen in bone; and finally, the third aim, to correlate the NIRS-derived water content in human cortical bone to structural properties determined by micro-computed tomography (micro-CT). Together these studies will establish the NIRS technique as a powerful tool to screen and monitor aging and diseased tissues in preclinical studies.
    • Negotiating Identities: An Interview Study and Autoethnography of Six Japanese American TESOL Professionals in Japan

      Casanave, Christine Pearson, 1944-; Beglar, David J.; Rosenkjar, Patrick; Churchill, Eton, 1964-; Motha, Suhanthie (Temple University. Libraries, 2014)
      In this interview study involving the analysis of narratives collected from Japanese American professionals teaching English to speakers of other languages (TESOL) who have lived more than ten years in Japan, I focus on how the participants negotiated their often contested identities in the TESOL context in Japan. I use the notion of identity negotiation narrowly defined as "struggles which occur when certain identity options are imposed or devalued, and others are unavailable or misunderstood" (Pavlenko & Blackledge, 2004, p. 20). Most Japanese Americans share similar phenotypes with the majority of Japanese nationals, creating many misconceptions about our linguistic competence in Japanese and English and ability to act appropriately within Japanese cultural norms. Educational settings are also an arena contributing to a simplistic Japanese/non-Japanese, native speaker/non-native speaker (NS/NNS) framework within which such encounters are defined. I intend to illuminate the underlying assumptions responsible for the misconceptions that continue to challenge their authenticity. This is in line with inquiry into the role of race in TESOL (Curtis & Romney, 2006; Kubota & Lin, 2006). The six participants were two men and four women, including myself. I conducted multiple interviews individually and in groups over a period of four years. I transcribed the narrative data into numbered lines and reworked selected parts into stanza form (Gee, 2005) or used block quotes to analyze the identity negotiation processes. For the autoethnography, I used intensive reflective writings done throughout the course of this project in addition to interview data in which I am the interviewer who also shares stories. Through multi-layered analyses (Sorsoli, 2007), I hope to illuminate what the individuals' narratives reflect about the contested nature of values held about language, ethnicity, race, and identity in the context of English teaching, learning, and use in Japan today. I suggest that the findings and conclusions from this study can be applied to other contexts in the world as well. It is therefore important for the TESOL professional to become an actively critical observer of how her work is affecting all the stakeholders, including her own self.