Internship at Kit.com - Health Diagnostics through Mail

Currently the most common way to run a diagnostic test is to go to a doctor\u27s office for a blood draw, but this has drawbacks - offices can be crowded, lead to exposure to illness, and take a large amount of time out of your day. At the Biotech startup company, Kit.com, we hope to provide the ability for clients to use our diagnostics kits in the comfort of their own home. Due to the use of the mail to deliver our kit anyone can use it and there are no needles involved to help assuage anxiety. We use a fringerprick test that uses lancets that provides a quick method that doesn\u27t require the user to see a needle. The amount of blood needed for our tests is approximately 700uL while conventional draws can take multiple milliliters. Some examples of some tests we provide are HbA1c, Triglyceride and multiple enzyme level panels. My role is to test the components of the kit for quality and to test the user experience with volunteers

PhD

dissertationTransport and permeability properties of the blood-cerebrospinal fluid and blood-brain barriers were determined by kinetic analysis of radioisotope uptake from the plasma into the central nervous system of adult and infant rats. For adult rats (5 wk of age), 36CI and 22Na uptake into the lateral ventricle (LVCP) and fourth ventricle (4VCP) choroid plexuses were resolved into two components, a fast component (t,½ 0.02-0.05 h) which represents isotope distribution within the extracellular and residual erythrocyte compartments and a slow component (t ½ 0.85-1.93 h) representing isotope movement into the epithelial cell compartment. Calculated LVCP and 4VCPcell [CI], 67 mmol/kg cell HO, were 3.9x greater than that predicted for passive distribution by the membrane potential. It is postulated that CI is actively transported into the choroid ependymal cell across the basolateral membrane; the energy for active CI transport may be the Na electrochemical potential gradient which is twice that of the CI electrochemical potential difference. 36CI and 22Na uptake into the cerebrospinal fluid (CSF) were resolved into two components, a fast component (t ½ 0.18 h, fractional volume 0.24) and a slow component (t ½ 1.2 h, fractional volume 0.76). Evidence suggests that the fast component represents isotope movement across the blood-CSF barrier, i.e., the choroid plexuses. The slow component may reflect isotope exchange primarily from brain extracellular fluid into the CSF. Cerebral cortex and cerebellum uptake of 36CI and 22 Na were resolved into two components. The fast component (t ½ 0.02-0.05 h, fractional volume 0.04-0.08) Is comprised of the vascular compartment and a small perivascular space. The slow component (t ½ 1.1-1.7 h, fractional volume 0.92-0.96) represents isotope movement across the blood-brain barrier into the brain extracellular and cellular compartments. The extracellular fluid volume of the cerebral cortex and cerebellum was estimated as ~13% from the initial slope of the brain space versus CSF space curve. Like the choroid plexuses, the glial cell compartment of the brain would appear to actively accumulate CI from 2-6x that predicted for passive distribution. The relative permeability of the blood-CSF and blood-brain barriers to 36CI, 22Na, and 3H-mannitol was determined by calculating permeability surface-area products (PA). Analysis of the PA values for all three isotopes indicates that the effective permeability of the choroidal epithelium (blood-CSF barrier) is significantly greater than that of the cerebral cortex or cerebellum capillary endothelium (blood-brain barrier). Analysis of radioisotope uptake by the 1- and 2-wk rat central nervous system revealed significant maturational differences from that of the 5-wk rat. The calculated LVCPand 4VCP cell [CI] and [Na] were markedly greater in the 1-wk than in the 5-wk rat. Likewise, a significant CSF fast component was not observed for radioisotope uptake at 1 wk of age. It is postulated that while the immature choroid plexus can actively accumulate CI across the basolateral membrane of the cell, the mechanisms which regulate CI exit from the choroidal cell into the CSF have not fully developed. Thus, at 1 wk, epithelial cell [CI] and [Na] were substantially greater than at 2 or 5 wk because ion transport into the choroidal cell across the basolateral membrane was not coupled with ion movement from the cell into the CSF. The onset of choroid plexus fluid secretion {~2 wk), as indicated by the volume of the CSF fast component, corresponds in time to the decrease in choroid plexus cell [CI] and [Na] (1-2 wk). Lastly, the cerebral cortex and cerebellum PA for all three radioisotopes decreased significantly between 1 and 5 wk of age (barrier tightening) while the CSF (fast component) PA to 36CI and 22Na increased with age (transepithelial choroid plexus NaCI transport)

Feet on the potential energy surface, head in the π clouds

The landscape of a potential energy surface is marked by chemically interesting features. Hills and valleys correspond to transition states and reactive intermediates; the deepest valley gives the most stable configuration. Mapping these features for individual molecules and for the interactions between molecules is one of the goals of computational chemistry. The dispersion energy is a weak attractive force in intermolecular interactions. Dispersion energy results from a purely quantum mechanical effect, in which instantaneous multipoles on one molecule induce multipoles on another. Among neutral atoms or molecules that lack permanent multipole moments, the dispersion interaction is the principal attractive force. Dispersion also plays a significant role in the interaction between molecules with diffuse π clouds. This interaction is often difficult to capture with standard computational chemistry methods, so a comparison of the results obtained with various methods is itself important. This work presents explorations of the potential energy surface of clusters of atoms and of the interactions between molecules. First, structures of small aluminum clusters are examined and classified as ground states, transition states, or higher-order saddle points. Subsequently, the focus shifts to dispersion-dominated π-π interactions when the potential energy surfaces of benzene, substituted benzene, and pyridine dimers are explored. Because DNA nucleotide bases can be thought of as substituted heterocycles, a natural extension of the substituted benzene and pyridine investigations is to model paired nucleotide bases. Finally, the success of the dispersion studies inspires the development of an extension to the computational method used, which will enable the dispersion energy to be modeled - and the potential energy surface explored - in additional chemical systems

The Meaning and Malleableness of Liberty from 1897-1945

This paper covers how the substance and meaning of liberty changed during the ending years of the Gilded Age (1870-1900) through the beginning ages of the Civil Rights Movement (1954-1968). Economic liberty took shape in the cases Allegeyer v. Louisiana (1897) and Lochner v. New York (1905). Civil liberties would take several more years to come into the Supreme Court’s jurisdiction. The case Gitlow v. New York (1925) began the establishment of incorporation of the Bill of Rights to the states, otherwise known as our fundamental liberties (note: The Supreme Court used selective incorporation, however). In the case U.S. v. Carolene Products (1938), the court stated that it would impose higher scrutiny to laws that violated the Bill of Rights. This paper attempts to rationalize that legal realism and sociological jurisprudence, both established by Roscoe Pound, changed the way we view liberty in the modern day. In a span of just under 50 years, the court retreated from substantive Due Process of economic liberty to substantive Due Process of civil liberty and human rights. Rulings such as Korematsu v. U.S. (1945), which established strict scrutiny, were the stepping stones of the growing Civil Rights Movement that would take the nation by storm from the mid-1950s until the end of the 1960s. Lastly, this paper argues that, while it may not be publicly known to all, Supreme Court decisions shape the way our laws are created, and thus, how our democratic society functions as a whole. We must not take our liberty for granted

PhD

dissertationTransport and permeability properties of the blood-cerebrospinal fluid and blood-brain barriers were determined by kinetic analysis of radioisotope uptake from the plasma into the central nervous system of adult and infant rats. For adult rats (5 wk of age), 36CI and 22Na uptake into the lateral ventricle (LVCP) and fourth ventricle (4VCP) choroid plexuses were resolved into two components, a fast component (t,½ 0.02-0.05 h) which represents isotope distribution within the extracellular and residual erythrocyte compartments and a slow component (t ½ 0.85-1.93 h) representing isotope movement into the epithelial cell compartment. Calculated LVCP and 4VCPcell [CI], 67 mmol/kg cell HO, were 3.9x greater than that predicted for passive distribution by the membrane potential. It is postulated that CI is actively transported into the choroid ependymal cell across the basolateral membrane; the energy for active CI transport may be the Na electrochemical potential gradient which is twice that of the CI electrochemical potential difference. 36CI and 22Na uptake into the cerebrospinal fluid (CSF) were resolved into two components, a fast component (t ½ 0.18 h, fractional volume 0.24) and a slow component (t ½ 1.2 h, fractional volume 0.76). Evidence suggests that the fast component represents isotope movement across the blood-CSF barrier, i.e., the choroid plexuses. The slow component may reflect isotope exchange primarily from brain extracellular fluid into the CSF. Cerebral cortex and cerebellum uptake of 36CI and 22 Na were resolved into two components. The fast component (t ½ 0.02-0.05 h, fractional volume 0.04-0.08) Is comprised of the vascular compartment and a small perivascular space. The slow component (t ½ 1.1-1.7 h, fractional volume 0.92-0.96) represents isotope movement across the blood-brain barrier into the brain extracellular and cellular compartments. The extracellular fluid volume of the cerebral cortex and cerebellum was estimated as ~13% from the initial slope of the brain space versus CSF space curve. Like the choroid plexuses, the glial cell compartment of the brain would appear to actively accumulate CI from 2-6x that predicted for passive distribution. The relative permeability of the blood-CSF and blood-brain barriers to 36CI, 22Na, and 3H-mannitol was determined by calculating permeability surface-area products (PA). Analysis of the PA values for all three isotopes indicates that the effective permeability of the choroidal epithelium (blood-CSF barrier) is significantly greater than that of the cerebral cortex or cerebellum capillary endothelium (blood-brain barrier). Analysis of radioisotope uptake by the 1- and 2-wk rat central nervous system revealed significant maturational differences from that of the 5-wk rat. The calculated LVCPand 4VCP cell [CI] and [Na] were markedly greater in the 1-wk than in the 5-wk rat. Likewise, a significant CSF fast component was not observed for radioisotope uptake at 1 wk of age. It is postulated that while the immature choroid plexus can actively accumulate CI across the basolateral membrane of the cell, the mechanisms which regulate CI exit from the choroidal cell into the CSF have not fully developed. Thus, at 1 wk, epithelial cell [CI] and [Na] were substantially greater than at 2 or 5 wk because ion transport into the choroidal cell across the basolateral membrane was not coupled with ion movement from the cell into the CSF. The onset of choroid plexus fluid secretion {~2 wk), as indicated by the volume of the CSF fast component, corresponds in time to the decrease in choroid plexus cell [CI] and [Na] (1-2 wk). Lastly, the cerebral cortex and cerebellum PA for all three radioisotopes decreased significantly between 1 and 5 wk of age (barrier tightening) while the CSF (fast component) PA to 36CI and 22Na increased with age (transepithelial choroid plexus NaCI transport)

Consequences of the Megafauna Extinction: Changes in Food Web Networks on the Edwards Plateau Across the Pleistocene-Holocene Transition

We are experiencing biodiversity loss due to climate change and human impacts, which is not only harmful to the environment but can also alter the composition of communities and interactions among species. The late Pleistocene experienced a loss of large-bodied mammals which resulted in significant changes in community structure due to changes in body size, diet, and species associations. The impact of these changes on species interactions and community structure across the Pleistocene-Holocene transition remains poorly understood. Using a robust data set of species composition, stable isotopes, body size, and climate variables, we constructed and compared ecological networks of mammal paleocommunities on the Edwards Plateau, Texas. One site, Hall’s Cave, has a temporal resolution that allows an in-depth analysis by separating the last 22,000 years into 16 time intervals. We measured the structure of food webs using modularity, and species contributions to modularity. Additionally for Hall’s Cave, we measured an index of node overlap and segregation for each time interval. We find consistent decreases in modularity across all sites with food webs shifting from having multiple clusters in the Pleistocene to fewer clusters in the Holocene. The less complex network post extinction is largely attributed to the loss of particular species interactions. In Hall’s Cave, we find node overlap increases and modularity decreases over time. Spearman-Rank correlation analyses indicate that changes in modularity were not driven by changes in species richness or climate change. The degree of node overlap shifted across the Pleistocene-Holocene transition and was significantly different from null model expectations in the Holocene but not in the Pleistocene. These results suggest that the transition from a modular network to a network of less complexity with an overlap of interacting species may have been driven by other factors that changed the food web, such as species composition. Thus, the change in mammal food web structure of Hall’s Cave was mainly a consequence of the megafauna extinctions. Advisors: S. Kathleen Lyons and Daizaburo Shizuk

Electron Affinity of Al13: A Correlated Electronic Structure Study

Neutral and anionic 13-atom aluminum clusters are studied with high-level, fully ab initio methods: second-order perturbation theory (MP2) and coupled cluster theory with singles, doubles, and perturbative triples (CCSD(T)). Energies and vibrational frequencies are reported for icosahedral and decahedral isomers, and are compared with density functional theory results. At the MP2 level of theory, with all of the basis sets employed, the icosahedral structure is energetically favored over the decahedral structure for both the neutral and anionic Al13 clusters. Hessian calculations imply that only the icosahedral structures are potential energy minima. The CCSD(T)/aug-cc-pVTZ adiabatic electron affinity of Al13 is found to be 3.57 eV, in excellent agreement with experiment