Alien Registration- Freedman, Benjamin (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/25306/thumbnail.jp

Multiscale Mechanical, Structural, And Compositional Response Of Tendon To Static And Dynamic Loading During Healing

The extracellular matrix (ECM) is a major component of the biomechanical environment with which tendon cells (tenocytes) interact. Alterations to matrix structural and mechanical properties due to mechanical loading may promote normal tendon homeostasis or create pathological conditions. For example, fatigue loading of tendon elevates collagen fiber waviness (crimp), which correlates linearly with tissue laxity. The tendon ECM may also be altered following tendon injury. Aberrant tissue phenotypes caused by tendon ruptures are exemplified not only at transcript and protein levels, but also can extend to include disorganized collagen structure, inferior mechanical properties, and reduced in vivo limb function in animals. This dissertation explores the interface between dynamic loading and tendon healing across multiple length scales using living tendon explants. This work begins to define the implications of macroscale mechanical loading on collagen structure and tenocyte response in uninjured and healing tendon, and provides a foundation for the development of new strategies to improve tendon healing. Ultimately, this work helps our understanding of tendon’s multiscale response to loading, provides a framework for the micromechanical environment that tenocytes interact in response to dynamic loading and healing, and lays important groundwork for benchmarks for tendon tissue engineering. The multiscale response to mechanical loading, which is a hallmark of clinical rehabilitation protocols, is necessary to determine the ramifications of various macroscale loading protocols. Additionally, these results provide benchmarks for the environments in which tendon cells may experience following cell delivery therapies. Several exciting future avenues of research are possible that would highly impact basic science research of tendon function and lead to potentially translatable approaches that could improve tendon injury onset and healing response. In conclusion, this dissertation provides a strong foundation on which future experimental and computational studies can build to fully elucidate the multiscale mechanisms that govern strain transfer in tendon

Histone H1 is essential for mitotic chromosome architecture and segregation in Xenopus laevis egg extracts.

During cell division, condensation and resolution of chromosome arms and the assembly of a functional kinetochore at the centromere of each sister chromatid are essential steps for accurate segregation of the genome by the mitotic spindle, yet the contribution of individual chromatin proteins to these processes is poorly understood. We have investigated the role of embryonic linker histone H1 during mitosis in Xenopus laevis egg extracts. Immunodepletion of histone H1 caused the assembly of aberrant elongated chromosomes that extended off the metaphase plate and outside the perimeter of the spindle. Although functional kinetochores assembled, aligned, and exhibited poleward movement, long and tangled chromosome arms could not be segregated in anaphase. Histone H1 depletion did not significantly affect the recruitment of known structural or functional chromosomal components such as condensins or chromokinesins, suggesting that the loss of H1 affects chromosome architecture directly. Thus, our results indicate that linker histone H1 plays an important role in the structure and function of vertebrate chromosomes in mitosis

Existence of Solutions to Boundary Value Problems on Infinite Intervals

In this talk, we will analyze boundary value problems on infinite intervals subject to generalized boundary conditions. In particular, results are obtained for problems in the differential equation setting for a wide variety of problems. For such problems, we establish sufficient conditions for the existence of solutions as well as a qualitative description of solutions according to a parameter. Conditions for solvability are obtained by employing the Lyapunov-Schmidt procedure and an application of the implicit function theorem

5 S,15 S-Dihydroperoxyeicosatetraenoic Acid (5,15-diHpETE) as a Lipoxin Intermediate: Reactivity and Kinetics with Human Leukocyte 5-Lipoxygenase, Platelet 12-Lipoxygenase, and Reticulocyte 15-Lipoxygenase-1.

The reaction of 5 S,15 S-dihydroperoxyeicosatetraenoic acid (5,15-diHpETE) with human 5-lipoxygenase (LOX), human platelet 12-LOX, and human reticulocyte 15-LOX-1 was investigated to determine the reactivity and relative rates of producing lipoxins (LXs). 5-LOX does not react with 5,15-diHpETE, although it can produce LXA4 when 15-HpETE is the substrate. In contrast, both 12-LOX and 15-LOX-1 react with 5,15-diHpETE, forming specifically LXB4. For 12-LOX and 5,15-diHpETE, the kinetic parameters are kcat = 0.17 s-1 and kcat/ KM = 0.011 μM-1 s-1 [106- and 1600-fold lower than those for 12-LOX oxygenation of arachidonic acid (AA), respectively]. On the other hand, for 15-LOX-1 the equivalent parameters are kcat = 4.6 s-1 and kcat/ KM = 0.21 μM-1 s-1 (3-fold higher and similar to those for 12-HpETE formation by 15-LOX-1 from AA, respectively). This contrasts with the complete lack of reaction of 15-LOX-2 with 5,15-diHpETE [Green, A. R., et al. (2016) Biochemistry 55, 2832-2840]. Our data indicate that 12-LOX is markedly inferior to 15-LOX-1 in catalyzing the production of LXB4 from 5,15-diHpETE. Platelet aggregation was inhibited by the addition of 5,15-diHpETE, with an IC50 of 1.3 μM; however, LXB4 did not significantly inhibit collagen-mediated platelet activation up to 10 μM. In summary, LXB4 is the primary product of 12-LOX and 15-LOX-1 catalysis, if 5,15-diHpETE is the substrate, with 15-LOX-1 being 20-fold more efficient than 12-LOX. LXA4 is the primary product with 5-LOX but only if 15-HpETE is the substrate. Approximately equal proportions of LXA4 and LXB4 are produced by 12-LOX but only if LTA4 is the substrate, as described previously [Sheppard, K. A., et al. (1992) Biochim. Biophys. Acta 1133, 223-234]

Substance Abuse via Legally Prescribed Drugs: The Case of Vicodin in the United States

Vicodin is the most commonly prescribed pain reliever in the United States. Research indicates that there are two million people who are currently abusing Vicodin, and the majority of those who abuse Vicodin were initially exposed to it via prescription. Our goal is to determine the most effective strategies for reducing the overall population of Vicodin abusers. More specifically, we focus on whether prevention methods aimed at educating doctors and patients on the potential for drug abuse or treatment methods implemented after a person abuses Vicodin will have a greater overall impact. We consider one linear and two non-linear compartmental models in which medical users of Vicodin can transition into the abuser compartment or leave the population by no longer taking the drug. Once Vicodin abusers, people can transition into a treatment compartment, with the possibility of leaving the population through successful completion of treatment or of relapsing and re-entering the abusive compartment. The linear model assumes no social interaction, while both non-linear models consider interaction. One considers interaction with abusers affecting the relapse rate, while the other assumes both this and an additional interaction between the number of abusers and the number of new prescriptions. Sensitivity analyses are conducted varying the rates of success of these intervention methods measured by the parameters to determine which strategy has the greatest impact on controlling the population of Vicodin abusers. From these models and analyses, we determine that manipulating parameters tied to prevention measures has a greater impact on reducing the population of abusers than manipulating parameters associated with treatment. We also note that increasing the rate at which abusers seek treatment affects the population of abusers more than the success rate of treatment itself

Encountering Ableism in the Moment

At colleges and universities in the United States, disability is typically addressed as a medicalized identity. Students must self-identify as having a disability to their postsecondary school in order to receive access to accommodations. They are also expected to communicate with faculty members about using accommodations in individual courses. Students report experiencing stigma and discrimination due to being required to disclose a disability status and negotiate with faculty members to use accommodations. This paper uses theoretical frameworks within the field of Disability Studies to investigate how university students engage in conversations with faculty members about accommodations. Students provide insight into the barriers to meaningful access to education that they encounter, and how they manage stigmatized social identities within the power dynamic of a student-faculty member relationship