Modeling Invariances in Inferotemporal Cell Tuning

In macaque inferotemporal cortex (IT), neurons have been found to respond selectively to complex shapes while showing broad tuning ("invariance") with respect to stimulus transformations such as translation and scale changes and a limited tuning to rotation in depth. Training monkeys with novel, paperclip-like objects, Logothetis et al. could investigate whether these invariance properties are due to experience with exhaustively many transformed instances of an object or if there are mechanisms that allow the cells to show response invariance also to previously unseen instances of that object. They found object-selective cells in anterior IT which exhibited limited invariance to various transformations after training with single object views. While previous models accounted for the tuning of the cells for rotations in depth and for their selectivity to a specific object relative to a population of distractor objects, the model described here attempts to explain in a biologically plausible way the additional properties of translation and size invariance. Using the same stimuli as in the experiment, we find that model IT neurons exhibit invariance properties which closely parallel those of real neurons. Simulations show that the model is capable of unsupervised learning of view-tuned neurons. The model also allows to make experimentally testable predictions regarding novel stimulus transformations and combinations of stimuli.

Modeling the Transport Sector: The Role of Existing Fuel Taxes in Climate Policy

Existing fuel taxes play a major role in determining the welfare effects of exempting the transportation sector from measures to control greenhouse gases. To study this phenomenon we modify the MIT Emissions Prediction and Policy Analysis (EPPA) model to disaggregate the household transportation sector. This improvement requires an extension of the GTAP data set that underlies the model. The revised and extended facility is then used to compare economic costs of cap-and-trade systems differentiated by sector, focusing on two regions: the USA where the fuel taxes are low, and Europe where the fuel taxes are high. We find that the interplay between carbon policies and pre-existing taxes leads to different results in these regions: in the USA exemption of transport from such a system would increase the welfare cost of achieving a national emissions target, while in Europe such exemptions will correct pre-existing distortions and reduce the cost.

Cell-line Engineering of Chinese Hamster Ovary Cells for Low-temperature Culture

Developments in mammalian cell culture and recombinant technology has allowed for the production of recombinant proteins for use as human therapeutics. Mammalian cell culture is typically operated at the physiological temperature of 37°. However, recent research has shown that the use of low-temperature conditions (30-33°) as a platform for cell-culture results in changes in cell characteristics, such as increased specific productivity and extended periods of cell viability, that can potentially improve the production of recombinant proteins. Furthermore, many recent reports have focused on investigating low-temperature mammalian cell culture of Chinese hamster ovary (CHO) cells, one of the principal cell-lines used in industrial production of recombinant proteins. Exposure to low ambient temperatures exerts an external stress on all living cells, and elicits a cellular response. This cold-stress response has been observed in bacteria, plants and mammals, and is regulated at the gene level. The exact genes and molecular mechanisms involved in the cold-stress response in prokaryotes and plants have been well studied. There are also various reports that detail the modification of cold-stress genes to improve the characteristics of bacteria or plant cells at low temperatures. However, there is very limited information on mammalian cold-stress genes or the related pathways governing the mammalian cold-stress response. This project seeks to investigate and characterise cold-stress genes that are differentially expressed during low-temperature culture of CHO cells, and to relate them to the various changes in cell characteristics observed in low-temperature culture of CHO cells. The gene information can then be used to modify CHO cell-lines for improved performance in the production of recombinant proteins.

Numerical comparison between Maxwell stress method and equivalent multipole approach for calculation of the dielectrophoretic force in octupolar cell traps

This work presents detailed numerical calculations of the dielectrophoretic force in octupolar traps designed for single-cell trapping. A trap with eight planar electrodes is studied for spherical and ellipsoidal particles using an indirect implementation of the boundary element method (BEM). Multipolar approximations of orders one to three are compared with the full Maxwell stress tensor (MST) calculation of the electrical force on spherical particles. Ellipsoidal particles are also studied, but in their case only the dipolar approximation is available for comparison with the MST solution. The results show that the full MST calculation is only required in the study of non-spherical particles.

Effect of Gas Sparging in Mammalian Cell Bioreactors

One of the major problems in the operations of mammalian cell bioreactors is the detrimental effect of gas sparging. Since the most convenient way to oxygenate any bioreactor is by gas sparging, this adverse effect has often been one of the limiting oxygen transport problems in both laboratory and industrial mammalian cell bioreactors. When one examines the literature on the effect of gas sparging on the death of mammalian cells, a great deal of confusions has been reported. It is not clear from the published literature as to the leading cause for gas-sparged related cell death. These confusions prevent the rational design and operations of mammalian cell bioreactors. In our laboratory, we have attempted to address this problem both fundamentally as well as attempt to obtain a general understanding on the adverse effect of gas sparging. Our analyses first examined the fluid shear associated with the various sections that the gas bubbles encounter during entrance, passage through the bioreactor and the final exit of the gas bubbles. Our analyses showed that the major damage of the mammalian cells by gas bubbles is due to the burst of the bubbles when exiting the bioreactor. It was also our hypothesis that the entrained cells in the liquid boundary layer of the gas bubble upon bursting is the major cause for cell death. We have corroborated this hypothesis by correlating the liquid entrainment with the cell death rate using results from our laboratory as well as other studies. Pluonic F-68, a weak surfactant, has routinely been used in laboratory and industrial bioreactors. In the past, the protective effect of Pluronic F-68 has never been shown as to why it is effective. In our research, we have data using microphotography which clearly demonstrated and corroborated our entrainment hypothesis is the major reason for the effectiveness of Pluronic F-68 in protecting the cells from gas-sparged related cell death.