ASU Scholarship Showcase

This paper studies the effect of targeted observations on state and parameter estimates determined with Kalman filter data assimilation (DA) techniques. We first provide an analytical result demonstrating that targeting observations within the Kalman filter for a linear model can significantly reduce state estimation error as opposed to fixed or randomly located observations. We next conduct observing system simulation experiments for a chaotic model of meteorological interest, where we demonstrate that the local ensemble transform Kalman filter (LETKF) with targeted observations based on largest ensemble variance is skillful in providing more accurate state estimates than the LETKF with randomly located observations. Additionally, we find that a hybrid ensemble Kalman filter parameter estimation method accurately updates model parameters within the targeted observation context to further improve state estimation.

A structurally and compositionally well-defined and spectrally tunable artificial light-harvesting system has been constructed in which multiple organic dyes attached to a three-arm-DNA nanostructure serve as an antenna conjugated to a photosynthetic reaction center isolated from Rhodobacter sphaeroides 2.4.1. The light energy absorbed by the dye molecules is transferred to the reaction center, where charge separation takes place. The average number of DNA three-arm junctions per reaction center was tuned from 0.75 to 2.35. This DNA-templated multichromophore system serves as a modular light-harvesting antenna that is capable of being optimized for its spectral properties, energy transfer efficiency, and photostability, allowing one to adjust both the size and spectrum of the resulting structures. This may serve as a useful test bed for developing nanostructured photonic systems.

Time-resolved fluorescence spectroscopy was used to explore the pathway and kinetics of energy transfer in photosynthetic membrane vesicles (chromatophores) isolated from Rhodobacter (Rba.) sphaeroides cells harvested 2, 4, 6 or 24 hours after a transition from growth in high to low level illumination. As previously observed, this light intensity transition initiates the remodeling of the photosynthetic apparatus and an increase in the number of light harvesting 2 (LH2) complexes relative to light harvesting 1 (LH1) and reaction center (RC) complexes. It has generally been thought that the increase in LH2 complexes served the purpose of increasing the overall energy transmission to the RC. However, fluorescence lifetime measurements and analysis in terms of energy transfer within LH2 and between LH2 and LH1 indicate that, during the remodeling time period measured, only a portion of the additional LH2 generated are well connected to LH1 and the reaction center. The majority of the additional LH2 fluorescence decays with a lifetime comparable to that of free, unconnected LH2 complexes. The presence of large LH2-only domains has been observed by atomic force microscopy in Rba. sphaeroides chromatophores (Bahatyrova et al., Nature, 2004, 430, 1058), providing structural support for the existence of pools of partially connected LH2 complexes. These LH2-only domains represent the light-responsive antenna complement formed after a switch in growth conditions from high to low illumination, while the remaining LH2 complexes occupy membrane regions containing mixtures of LH2 and LH1–RC core complexes. The current study utilized a multi-parameter approach to explore the fluorescence spectroscopic properties related to the remodeling process, shedding light on the structure-function relationship of the photosynthetic assembles. Possible reasons for the accumulation of these largely disconnected LH2-only pools are discussed.

The effects of urbanization on ozone levels have been widely investigated over cities primarily located in temperate and/or humid regions. In this study, nested WRF-Chem simulations with a finest grid resolution of 1 km are conducted to investigate ozone concentrations O₃ due to urbanization within cities in arid/semi-arid environments. First, a method based on a shape preserving Monotonic Cubic Interpolation (MCI) is developed and used to downscale anthropogenic emissions from the 4 km resolution 2005 National Emissions Inventory (NEI05) to the finest model resolution of 1 km. Using the rapidly expanding Phoenix metropolitan region as the area of focus, we demonstrate the proposed MCI method achieves ozone simulation results with appreciably improved correspondence to observations relative to the default interpolation method of the WRF-Chem system. Next, two additional sets of experiments are conducted, with the recommended MCI approach, to examine impacts of urbanization on ozone production: (1) the urban land cover is included (i.e., urbanization experiments) and, (2) the urban land cover is replaced with the region's native shrubland. Impacts due to the presence of the built environment on O₃ are highly heterogeneous across the metropolitan area. Increased near surface O₃ due to urbanization of 10–20 ppb is predominantly a nighttime phenomenon while simulated impacts during daytime are negligible. Urbanization narrows the daily O₃ range (by virtue of increasing nighttime minima), an impact largely due to the region's urban heat island. Our results demonstrate the importance of the MCI method for accurate representation of the diurnal profile of ozone, and highlight its utility for high-resolution air quality simulations for urban areas.

Background:
Ketogenic diets are high fat and low carbohydrate or very low carbohydrate diets, which render high production of ketones upon consumption known as nutritional ketosis (NK). Ketosis is also produced during fasting periods, which is known as fasting ketosis (FK). Recently, the combinations of NK and FK, as well as NK alone, have been used as resources for weight loss management and treatment of epilepsy.

Methods:
A crossover study design was applied to 11 healthy individuals, who maintained moderately sedentary lifestyle, and consumed three types of diet randomly assigned over a three-week period. All participants completed the diets in a randomized and counterbalanced fashion. Each weekly diet protocol included three phases: Phase 1 - A mixed diet with ratio of fat: (carbohydrate + protein) by mass of 0.18 or the equivalence of 29% energy from fat from Day 1 to Day 5. Phase 2- A mixed or a high-fat diet with ratio of fat: (carbohydrate + protein) by mass of approximately 0.18, 1.63, or 3.80 on Day 6 or the equivalence of 29%, 79%, or 90% energy from fat, respectively. Phase 3 - A fasting diet with no calorie intake on Day 7. Caloric intake from diets on Day 1 to Day 6 was equal to each individual’s energy expenditure. On Day 7, ketone buildup from FK was measured.

Results:
A statistically significant effect of Phase 2 (Day 6) diet was found on FK of Day 7, as indicated by repeated analysis of variance (ANOVA), F(2,20) = 6.73, p < 0.0058. Using a Fisher LDS pair-wise comparison, higher significant levels of acetone buildup were found for diets with 79% fat content and 90% fat content vs. 29% fat content (with p = 0.00159**, and 0.04435**, respectively), with no significant difference between diets with 79% fat content and 90% fat content. In addition, independent of the diet, a significantly higher ketone buildup capability of subjects with higher resting energy expenditure (R[superscript 2] = 0.92), and lower body mass index (R[superscript 2] = 0.71) was observed during FK.

Many drugs are effective in the early stage of treatment, but patients develop drug resistance after a certain period of treatment, causing failure of the therapy. An important example is Herceptin, a popular monoclonal antibody drug for breast cancer by specifically targeting human epidermal growth factor receptor 2 (Her2). Here we demonstrate a quantitative binding kinetics analysis of drug-target interactions to investigate the molecular scale origin of drug resistance. Using a surface plasmon resonance imaging, we measured the in situ Herceptin-Her2 binding kinetics in single intact cancer cells for the first time, and observed significantly weakened Herceptin-Her2 interactions in Herceptin-resistant cells, compared to those in Herceptin-sensitive cells. We further showed that the steric hindrance of Mucin-4, a membrane protein, was responsible for the altered drug-receptor binding. This effect of a third molecule on drug-receptor interactions cannot be studied using traditional purified protein methods, demonstrating the importance of the present intact cell-based binding kinetics analysis.

An interesting occurrence of a Rossby wave breaking event observed during the VORCORE experiment is presented and explained. Twenty-seven balloons were launched inside the Antarctic polar vortex. Almost all of these balloons evolved in the stratosphere around 500K within the vortex, except the one launched on 28 October 2005. In this case, the balloon was caught within a tongue of high potential vorticity (PV), and was ejected from the polar vortex. The evolution of this event is studied for the period between 19 and 25 November 2005. It is found that at the beginning of this period, the polar vortex experienced distortions due to the presence of Rossby waves. Then, these waves break and a tongue of high PV develops. On 25 November, the tongue became separated from the vortex and the balloon was ejected into the surf zone. Lagrangian simulations demonstrate that the air masses surrounding the balloon after its ejection were originating from the vortex edge. The wave breaking and the development of the tongue are confined within a region where a planetary Quasi-Stationary Wave 1 (QSW1) induces wind speeds with weaker values. The QSW1 causes asymmetry in the wind speed and the horizontal PV gradient along the edge of the polar vortex, resulting in a localized jet. Rossby waves with smaller scales propagating on top of this jet amplify as they enter the jet exit region and then break. The role of the QSW1 on the formation of the weak flow conditions that caused the non-linear wave breaking observed near the vortex edge is confirmed by three-dimensional numerical simulations using forcing with and without the contribution of the QSW1.

There are an increasing variety of applications in which peptides are both synthesized and used attached to solid surfaces. This has created a need for high throughput sequence analysis directly on surfaces. However, common sequencing approaches that can be adapted to surface bound peptides lack the throughput often needed in library-based applications. Here we describe a simple approach for sequence analysis directly on solid surfaces that is both high speed and high throughput, utilizing equipment available in most protein analysis facilities. In this approach, surface bound peptides, selectively labeled at their N-termini with a positive charge-bearing group, are subjected to controlled degradation in ammonia gas, resulting in a set of fragments differing by a single amino acid that remain spatially confined on the surface they were bound to. These fragments can then be analyzed by MALDI mass spectrometry, and the peptide sequences read directly from the resulting spectra.

Exposure to fine particles can cause various diseases, and an easily accessible method to monitor the particles can help raise public awareness and reduce harmful exposures. Here we report a method to estimate PM air pollution based on analysis of a large number of outdoor images available for Beijing, Shanghai (China) and Phoenix (US). Six image features were extracted from the images, which were used, together with other relevant data, such as the position of the sun, date, time, geographic information and weather conditions, to predict PM_2.5 index. The results demonstrate that the image analysis method provides good prediction of PM_2.5 indexes, and different features have different significance levels in the prediction.

Background: Chemistry and particularly enzymology at surfaces is a topic of rapidly growing interest, both in terms of its role in biological systems and its application in biocatalysis. Existing protein immobilization approaches, including noncovalent or covalent attachments to solid supports, have difficulties in controlling protein orientation, reducing nonspecific absorption and preventing protein denaturation. New strategies for enzyme immobilization are needed that allow the precise control over orientation and position and thereby provide optimized activity.

Methodology/Principal Findings: A method is presented for utilizing peptide ligands to immobilize enzymes on surfaces with improved enzyme activity and stability. The appropriate peptide ligands have been rapidly selected from high-density arrays and when desirable, the peptide sequences were further optimized by single-point variant screening to enhance both the affinity and activity of the bound enzyme. For proof of concept, the peptides that bound to β-galactosidase and optimized its activity were covalently attached to surfaces for the purpose of capturing target enzymes. Compared to conventional methods, enzymes immobilized on peptide-modified surfaces exhibited higher specific activity and stability, as well as controlled protein orientation.

Conclusions/Significance: A simple method for immobilizing enzymes through specific interactions with peptides anchored on surfaces has been developed. This approach will be applicable to the immobilization of a wide variety of enzymes on surfaces with optimized orientation, location and performance, and provides a potential mechanism for the patterned self-assembly of multiple enzymes on surfaces.