Biophysical Studies of Transmembrane Helix Dimerization

My research lab works towards the understanding of the physical and chemical principles governing the interaction of membrane proteins. Of particular interest is the role of the transmembrane domains in these interactions. The focus, thus far, has been on fibroblast growth factor receptors and mucin proteins and the formation of dimers. These membrane proteins are important because they regulate many vital cellular processes. Furthermore, diseases may arise when homo- and heterodimerization are not controlled properly due to mutations or overexpression of the membrane protein. Thus, these studies may provide useful information towards the development of better therapeutics. I will present two different methodologies to measure dimerization between transmembrane helices, and how they can be used to obtain thermodynamic and structural information

Large-Scale Spectroscopic Mapping of the ρ\rho Ophiuchi Molecular Cloud Complex I. The C2_{2}H to N2_2H+^+ Ratio as a Signpost of Cloud Characteristics

We present 2.5-square-degree C$_{2}$H N=1-0 and N$_2$H$^+$ J=1-0 maps of the $\rho$ Ophiuchi molecular cloud complex. These are the first large-scale maps of the $\rho$ Ophiuchi molecular cloud complex with these two tracers. The C$_{2}$H emission is spatially more extended than the N$_2$H$^+$ emission. One faint N$_2$H$^+$ clump Oph-M and one C$_{2}$H ring Oph-RingSW are identified for the first time. The observed C$_{2}$H to N$_{2}$H$^{+}$ abundance ratio ([C$_{2}$H]/[N$_{2}$H$^{+}$]) varies between 5 and 110. We modeled the C$_{2}$H and N$_2$H$^+$ abundances with 1-D chemical models which show a clear decline of [C$_2$H]/[N$_2$H$^+$] with chemical age. Such an evolutionary trend is little affected by temperatures when they are below 40 K. At high density (n$_H$ $>$ 10$^5$ cm$^{-3}$), however, the time it takes for the abundance ratio to drop at least one order of magnitude becomes less than the dynamical time (e.g., turbulence crossing time $\rm \sim$10$^5$ years). The observed [C$_2$H]/[N$_2$H$^+$] difference between L1688 and L1689 can be explained by L1688 having chemically younger gas in relatively less dense regions. The observed [C$_{2}$H]/[N$_{2}$H$^{+}$] values are the results of time evolution, accelerated at higher densities. For the relative low density regions in L1688 where only C$_2$H emission was detected, the gas should be chemically younger.Comment: Accepted by ApJ, 45 pages, 10 figure

State-space based mass event-history model I: many decision-making agents with one target

A dynamic decision-making system that includes a mass of indistinguishable agents could manifest impressive heterogeneity. This kind of nonhomogeneity is postulated to result from macroscopic behavioral tactics employed by almost all involved agents. A State-Space Based (SSB) mass event-history model is developed here to explore the potential existence of such macroscopic behaviors. By imposing an unobserved internal state-space variable into the system, each individual's event-history is made into a composition of a common state duration and an individual specific time to action. With the common state modeling of the macroscopic behavior, parametric statistical inferences are derived under the current-status data structure and conditional independence assumptions. Identifiability and computation related problems are also addressed. From the dynamic perspectives of system-wise heterogeneity, this SSB mass event-history model is shown to be very distinct from a random effect model via the Principle Component Analysis (PCA) in a numerical experiment. Real data showing the mass invasion by two species of parasitic nematode into two species of host larvae are also analyzed. The analysis results not only are found coherent in the context of the biology of the nematode as a parasite, but also include new quantitative interpretations.Comment: Published in at http://dx.doi.org/10.1214/08-AOAS189 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Tracing the Ingredients for a Habitable Earth from Interstellar Space through Planet Formation

We use the C/N ratio as a monitor of the delivery of key ingredients of life to nascent terrestrial worlds. Total elemental C and N contents, and their ratio, are examined for the interstellar medium, comets, chondritic meteorites and terrestrial planets; we include an updated estimate for the Bulk Silicate Earth (C/N = 49.0 +/- 9.3). Using a kinetic model of disk chemistry, and the sublimation/condensation temperatures of primitive molecules, we suggest that organic ices and macro-molecular (refractory or carbonaceous dust) organic material are the likely initial C and N carriers. Chemical reactions in the disk can produce nebular C/N ratios of ~1-12, comparable to those of comets and the low end estimated for planetesimals. An increase of the C/N ratio is traced between volatile-rich pristine bodies and larger volatile-depleted objects subjected to thermal/accretional metamorphism. The C/N ratios of the dominant materials accreted to terrestrial planets should therefore be higher than those seen in carbonaceous chondrites or comets. During planetary formation, we explore scenarios leading to further volatile loss and associated C/N variations owing to core formation and atmospheric escape. Key processes include relative enrichment of nitrogen in the atmosphere and preferential sequestration of carbon by the core. The high C/N BSE ratio therefore is best satisfied by accretion of thermally processed objects followed by large-scale atmospheric loss. These two effects must be more profound if volatile sequestration in the core is effective. The stochastic nature of these processes hints that the surface/atmospheric abundances of biosphere-essential materials will likely be variable.Comment: Accepted by PNAS per http://www.pnas.org/content/early/2015/07/01/1500954112.abstract?sid=9fd8abea-9d33-46d8-b755-217d10b1c24