Development of Spectroscopic Methods for Dynamic Cellular Level Study of Biochemical Kinetics and Disease Progression

One of the current fundamental objectives in biomedical research is understanding molecular and cellular mechanisms of disease progression. Recent work in genetics support the stochastic nature of disease progression on the single cell level. For example, recent work has demonstrated that cancer as a disease state is reached after the accumulation of damages that result in genetic errors. Other diseases like Huntingtons, Parkinsons, Alzheimers, cardiovascular disease are developed over time and their cellular mechanisms of disease transition are largely unknown. Modern techniques of disease characterization are perturbative, invasive and fully destructive to biological samples. Many methods need a probe or enhancement to take data which alters the biochemistry of the cells and may not be a true representations of cellular mechanisms. Current methods of characterizing disease progression cannot measure dynamics of a process but rely on an average state of a system at a fixed endpoint. They track cellular changes at a population level that rely on static ensemble averages that compare the same population at different time points or populations exposed to different stimuli. Ensemble averaging obscures spatiotemporal and dynamic molecular and cellular mechanism information by only measuring changes before and after disease transitions which neglects mechanistic information. This type of snap shot measurement contains no information regarding the transition into a disease state. The use of an ensemble averages ignores single cell level changes by assuming cells in a population are similar. In reality individual cell-to-cell variability in the same cell population can cause one cell to transition to disease state while another cell does not. Fluctuations are indicators of disease and if cellular processes are not studied spatiotemporally then key molecular changes are undetected. If the path to disease progression is known on an individual cell level, then treatments can be modified to alleviate or prevent disease through early detection. The aim of this thesis is to quantitatively and dynamically measure a biomedical sample on the single cell level without destroying or manipulating it significantly to characterize cellular mechanisms. The technique developed uses microRaman Spectroscopy to analyze molecular signatures of single cells and compare differences between signatures of cells in different populations

Detection of Galactic Center source G2 at 3.8 μ\mum during periapse passage

We report new observations of the Galactic Center source G2 from the W. M. Keck Observatory. G2 is a dusty red object associated with gas that shows tidal interactions as it nears closest approach with the Galaxy's central black hole. Our observations, conducted as G2 passed through periapse, were designed to test the proposal that G2 is a 3 earth mass gas cloud. Such a cloud should be tidally disrupted during periapse passage. The data were obtained using the Keck II laser guide star adaptive optics system (LGSAO) and the facility near-infrared camera (NIRC2) through the K' [2.1 $\mu$m] and L' [3.8 $\mu$m] broadband filters. Several results emerge from these observations: 1) G2 has survived its closest approach to the black hole as a compact, unresolved source at L'; 2) G2's L' brightness measurements are consistent with those over the last decade; 3) G2's motion continues to be consistent with a Keplerian model. These results rule out G2 as a pure gas cloud and imply that G2 has a central star. This star has a luminosity of $\sim$30 $L_{\odot}$ and is surrounded by a large ($\sim$2.6 AU) optically thick dust shell. The differences between the L' and Br-$\gamma$ observations can be understood with a model in which L' and Br-$\gamma$ emission arises primarily from internal and external heating, respectively. We suggest that G2 is a binary star merger product and will ultimately appear similar to the B-stars that are tightly clustered around the black hole (the so-called S-star cluster).Comment: Accepted by ApJ Letters, 2014 October 1

A population of dust-enshrouded objects orbiting the Galactic black hole

The central 0.1 parsecs of the Milky Way host a supermassive black hole identified with the position of the radio and infrared source Sagittarius A*, a cluster of young, massive stars (the S stars) and various gaseous features. Recently, two unusual objects have been found to be closely orbiting Sagittarius A*: the so-called G sources, G1 and G2. These objects are unresolved (having a size of the order of 100 astronomical units, except at periapse, where the tidal interaction with the black hole stretches them along the orbit) and they show both thermal dust emission and line emission from ionized gas. G1 and G2 have generated attention because they appear to be tidally interacting with the supermassive Galactic black hole, possibly enhancing its accretion activity. No broad consensus has yet been reached concerning their nature: the G objects show the characteristics of gas and dust clouds but display the dynamical properties of stellar-mass objects. Here we report observations of four additional G objects, all lying within 0.04 parsecs of the black hole and forming a class that is probably unique to this environment. The widely varying orbits derived for the six G objects demonstrate that they were commonly but separately formed

3d Tissue Engineered In Vitro Models Of Cancer In Bone.

Biological models are necessary tools for gaining insight into underlying mechanisms governing complex pathologies such as cancer in the bone. Models range fro

A population of dust-enshrouded objects orbiting the Galactic black hole.

The central 0.1 parsecs of the Milky Way host a supermassive black hole identified with the position of the radio and infrared source Sagittarius A* (refs. 1,2), a cluster of young, massive stars (the S stars3) and various gaseous features4,5. Recently, two unusual objects have been found to be closely orbiting Sagittarius A*: the so-called G sources, G1 and G2. These objects are unresolved (having a size of the order of 100 astronomical units, except at periapse, where the tidal interaction with the black hole stretches them along the orbit) and they show both thermal dust emission and line emission from ionized gas6-10. G1 and G2 have generated attention because they appear to be tidally interacting with the supermassive Galactic black hole, possibly enhancing its accretion activity. No broad consensus has yet been reached concerning their nature: the G objects show the characteristics of gas and dust clouds but display the dynamical properties of stellar-mass objects. Here we report observations of four additional G objects, all lying within 0.04 parsecs of the black hole and forming a class that is probably unique to this environment. The widely varying orbits derived for the six G objects demonstrate that they were commonly but separately formed