Undergraduate Research Opportunities Program (UROP)
http://hdl.handle.net/1853/12294
UROP assists undergraduate students in finding research opportunities of quality and substance.Sat, 13 Aug 2022 15:43:57 GMT2022-08-13T15:43:57ZHsp90 and the Evolution of Novel Cellular Differentiation
http://hdl.handle.net/1853/66764
Hsp90 and the Evolution of Novel Cellular Differentiation
Cheng, Vivian
Cellular differentiation is a prerequisite for complex multicellular life, yet little is known about how it evolves de novo. Several mechanisms may explain how early multicellular organisms evolved to perform cell-specific roles. In this work, I explore the potential role of cellular aging in driving age-dependent differences that evolve to become co-opted for a novel role in cellular differentiation. Specifically, I am examining how, in the snowflake yeast model system of nascent multicellularity, the Hsp90 class chaperone proteins have evolved to act in a novel age-dependent manner, thus driving the emergence of adaptive differences in protein activity among cells.
http://hdl.handle.net/1853/66764Cheng, VivianCellular differentiation is a prerequisite for complex multicellular life, yet little is known about how it evolves de novo. Several mechanisms may explain how early multicellular organisms evolved to perform cell-specific roles. In this work, I explore the potential role of cellular aging in driving age-dependent differences that evolve to become co-opted for a novel role in cellular differentiation. Specifically, I am examining how, in the snowflake yeast model system of nascent multicellularity, the Hsp90 class chaperone proteins have evolved to act in a novel age-dependent manner, thus driving the emergence of adaptive differences in protein activity among cells.On the Rank of Random, Symmetric Matrices over Z_2 via Random Graphs
http://hdl.handle.net/1853/66763
On the Rank of Random, Symmetric Matrices over Z_2 via Random Graphs
Raghavan, Aaditya
It is well-known that the game of \textit{Lights Out} on a graph $G$ with $|V(G)| = n$ is universally solvable if and only if the sum of the adjacency matrix of $G$ and the identity matrix $I_{n}$ is invertible over $\Z_2$. Denoting $G(n, 1/2)$ to be a graph on $n$ vertices chosen uniformly at random (each edge is chosen to be included or not independently with probability $1/2$), Forrest and Manno conjectured that as $n$ goes to infinity, the probability that $G(n, 1/2)$ is universally solvable is roughly $0.419$. We derive an explicit formula for this probability which, as a consequence, yields a more precise asymptotic probability. Moreover, we show that the probability that a random, symmetric matrix $M$ in $\Z_2^{n \times n}$ is invertible does not depend on the distribution of 0's and 1's along the main diagonal: we prove that the probabilities are identical for any given 0-1 distribution along the main diagonal over all matrices in $\Z_2^{n \times n}$ if $n$ is even, and over all matrices in $\Z_2^{n \times n}$ with at least one 1 along the main diagonal if $n$ is odd. We also develop expressions for the probability that, for $r \in \N$, $M$ has nullity $2r+1$ in the case that $n$ is odd, and $2r$ in the case that $n$ is even, in terms of closely related quantities.
http://hdl.handle.net/1853/66763Raghavan, AadityaIt is well-known that the game of \textit{Lights Out} on a graph $G$ with $|V(G)| = n$ is universally solvable if and only if the sum of the adjacency matrix of $G$ and the identity matrix $I_{n}$ is invertible over $\Z_2$. Denoting $G(n, 1/2)$ to be a graph on $n$ vertices chosen uniformly at random (each edge is chosen to be included or not independently with probability $1/2$), Forrest and Manno conjectured that as $n$ goes to infinity, the probability that $G(n, 1/2)$ is universally solvable is roughly $0.419$. We derive an explicit formula for this probability which, as a consequence, yields a more precise asymptotic probability. Moreover, we show that the probability that a random, symmetric matrix $M$ in $\Z_2^{n \times n}$ is invertible does not depend on the distribution of 0's and 1's along the main diagonal: we prove that the probabilities are identical for any given 0-1 distribution along the main diagonal over all matrices in $\Z_2^{n \times n}$ if $n$ is even, and over all matrices in $\Z_2^{n \times n}$ with at least one 1 along the main diagonal if $n$ is odd. We also develop expressions for the probability that, for $r \in \N$, $M$ has nullity $2r+1$ in the case that $n$ is odd, and $2r$ in the case that $n$ is even, in terms of closely related quantities.The effects of AT-RvD1 delivery on SPM metabolism, myeloid recruitment, and myogenesis in a murine model of Volumetric Muscle Loss injury
http://hdl.handle.net/1853/66762
The effects of AT-RvD1 delivery on SPM metabolism, myeloid recruitment, and myogenesis in a murine model of Volumetric Muscle Loss injury
Pittman, Frank S.
Volumetric Muscle Loss injury (VML) is the partial ablation of skeletal muscle, usually on the extremities, sustained through traumatic or surgical means, such as motor vehicle accidents, military combat, or surgical resection. The frank loss of musculature characteristic of VML sufficiently disrupts or eliminates the wound’s endogenous repair mechanisms such that healing becomes virtually impossible 1,2. VML patients must deal with permanent functional impairments, chronic inflammation, and chronic pain 1. Current clinical strategies for VML treatment include muscle flap autografts and free tissue transfer that, while salvaging the injured limb, are often no better than amputation in terms of functional improvement and patient quality of life 3,4. Much research in the field has been focused on overcoming the challenges and deficits associated with this clinical gold-standard. Biomaterial strategies using decellularized extracellular matrix (ECM) derived from skeletal muscle, porcine small intestinal submucosa (SIS), and urinary bladder matrix (UBM) have been extensively studied, with multiple FDA-approved products available for clinical use 5–7.
However, these studies continue to show that minimal levels of physiologically-relevant muscle fibers are regenerated in both human and animal trials of acellular matrices. Instead, regenerated tissue has been overwhelmingly composed of non-functional and non-contractile fibrotic and adipose tissue 6. Common between both the clinical gold standards and the acellular matrix strategies being studied is the over-looking of the inhospitable microenvironment caused by persistent inflammation that serves to activate fibrotic pathways of regeneration 1,7. Thus, the need for an alternative strategy that targets this pathological inflammation and results in better long-term functional outcomes for patients after severe extremity trauma is clear.
http://hdl.handle.net/1853/66762Pittman, Frank S.Volumetric Muscle Loss injury (VML) is the partial ablation of skeletal muscle, usually on the extremities, sustained through traumatic or surgical means, such as motor vehicle accidents, military combat, or surgical resection. The frank loss of musculature characteristic of VML sufficiently disrupts or eliminates the wound’s endogenous repair mechanisms such that healing becomes virtually impossible 1,2. VML patients must deal with permanent functional impairments, chronic inflammation, and chronic pain 1. Current clinical strategies for VML treatment include muscle flap autografts and free tissue transfer that, while salvaging the injured limb, are often no better than amputation in terms of functional improvement and patient quality of life 3,4. Much research in the field has been focused on overcoming the challenges and deficits associated with this clinical gold-standard. Biomaterial strategies using decellularized extracellular matrix (ECM) derived from skeletal muscle, porcine small intestinal submucosa (SIS), and urinary bladder matrix (UBM) have been extensively studied, with multiple FDA-approved products available for clinical use 5–7.
However, these studies continue to show that minimal levels of physiologically-relevant muscle fibers are regenerated in both human and animal trials of acellular matrices. Instead, regenerated tissue has been overwhelmingly composed of non-functional and non-contractile fibrotic and adipose tissue 6. Common between both the clinical gold standards and the acellular matrix strategies being studied is the over-looking of the inhospitable microenvironment caused by persistent inflammation that serves to activate fibrotic pathways of regeneration 1,7. Thus, the need for an alternative strategy that targets this pathological inflammation and results in better long-term functional outcomes for patients after severe extremity trauma is clear.Measuring Cerebral Blood Flow in a Mouse Model of Alzheimer's Disease
http://hdl.handle.net/1853/66761
Measuring Cerebral Blood Flow in a Mouse Model of Alzheimer's Disease
Daniel, Christy
Mild traumatic brain injuries (mTBIs), which are defined by an absence of overt structural damage in the brain have been associated with an increased risk of Alzheimer's Disease when sustained multiple times over an interval. Within mTBI, indirect evidence suggests that persistent post-concussive symptoms may be linked to reduced cerebral blood flow (CBF), of which deficits have been observed in cases of Alzheimer's Disease.
Diffuse correlation spectroscopy (DCS) is a non-invasive optical method that uses near-infrared light to measure fluctuations in intensity that are caused by moving red blood cells that can be used to measure cerebral blood flow (CBF) in C57bl/6 mice. This dissertation will adapt this novel protocol to a mouse model of Alzheimer’s Disease (3xTg). This strain will be utilized due to its accelerated AD pathology and the presence of literature that have observed impairments in CVR, CBF, among other biomarkers of Alzheimer’s Disease and traumatic brain injury. Given the smaller size of the 3xTg mice compared to C57bl/6, the DCS optical sensor must be modified. Herein, the design of a smaller sensor is detailed, along with a series of validation tests, which include measurements on a liquid phantom with known flow properties and on a pilot cohort of four 6–7-month-old 3xTg mice (2 males, 2 females). This data provides the foundational work to characterize the feasibility of DCS as a technique to monitor CBF and CVR in 3xTg mice for future experiments.
http://hdl.handle.net/1853/66761Daniel, ChristyMild traumatic brain injuries (mTBIs), which are defined by an absence of overt structural damage in the brain have been associated with an increased risk of Alzheimer's Disease when sustained multiple times over an interval. Within mTBI, indirect evidence suggests that persistent post-concussive symptoms may be linked to reduced cerebral blood flow (CBF), of which deficits have been observed in cases of Alzheimer's Disease.
Diffuse correlation spectroscopy (DCS) is a non-invasive optical method that uses near-infrared light to measure fluctuations in intensity that are caused by moving red blood cells that can be used to measure cerebral blood flow (CBF) in C57bl/6 mice. This dissertation will adapt this novel protocol to a mouse model of Alzheimer’s Disease (3xTg). This strain will be utilized due to its accelerated AD pathology and the presence of literature that have observed impairments in CVR, CBF, among other biomarkers of Alzheimer’s Disease and traumatic brain injury. Given the smaller size of the 3xTg mice compared to C57bl/6, the DCS optical sensor must be modified. Herein, the design of a smaller sensor is detailed, along with a series of validation tests, which include measurements on a liquid phantom with known flow properties and on a pilot cohort of four 6–7-month-old 3xTg mice (2 males, 2 females). This data provides the foundational work to characterize the feasibility of DCS as a technique to monitor CBF and CVR in 3xTg mice for future experiments.