Hereditary hemochromatosis (HH) is a prevalent genetic disorder that results in the daily excess absorption of dietary iron. If untreated this disease leads to systemic organ failure and death. HH is caused by mutations to the gene coding for a protein called HFE, a type I transmembrane glycoprotein with a demonstrated role in regulating cellular iron homeostasis. HFE binds to the cell-surface receptor transferrin receptor (TfR), a dimeric type II transmembrane glycoprotein responsible for iron uptake into most mammalian cell types. TfR binds iron-loaded transferrin (Fe-Tf) from the blood and transports it to acidic recycling endosomes where iron is released from Fe-Tf in a TfR-facilitated process. Iron-free transferrin (apo-Tf) remains bound to TfR and is recycled to the cell surface, where apo-Tf rapidly dissociates from TfR upon exposure to the basic pH of blood. HFE and Fe-Tf can bind simultaneously to TfR to form a ternary complex, but HFE binding to TfR lowers the apparent affinity of the Fe-Tf/TfR interaction. This reduction could result from direct competition between HFE and Fe-Tf for receptor binding sites, from negative cooperativity, or both. We sought to understand the mechanism of HFE, Fe-Tf, and apo-Tf binding by TfR to help define HFE's role in iron homeostasis. We determined the binding constants for HFE, Fe-Tf, and apo-Tf to an extensive set of site-directed TfR mutants and discovered that HFE and Tf bind to an overlapping site on TfR, indicating the two proteins compete with each other for receptor binding. The mutagenesis results also identified differences in the contact points between TfR and the two forms of Tf, Fe-Tf and apo-Tf. By combining the mutations that are required for apo-Tf, but not Fe-Tf, binding we find that a highly conserved hydrophobic patch on the TfR surface is required for the receptor-mediated stimulation of iron release from Fe-Tf. From these data we propose a structure-based model for the mechanism of TfR-assisted iron release.
It’s March 2005 and Martha Stewart is getting out of jail. As celebrities’ personal lives have become media worthy, Newsweek publishes her coming out from behind a red curtain on the cover. From this curtain, which represents her time in a minimum?security prison for insider trading, emerges the new trimmer, healthier looking Martha. This new trimmer body represents the overall reformation that Stewart experienced behind bars. There is a catch. Yes, that is Martha Stewart’s head, but the body belongs to a model. This is in fact a photo?illustration. A new term created for the age of digital technology, a photo illustration is one that is altered to the point that the editors deem it is no longer ethical to consider it a photograph. Yet, in order to find out that this image is in fact a photo?illustration, and not a photograph, one has to flip to the third page and read the fine print. This photo is a compilation of things that do exist, to form a person who never existed in this form, and it looks entirely believable. In the age of digital media this image is not the exception to the norm—it is the norm. We often assume that photographs do not need interpretation, especially in a journalistic context where it is assumed that they record the reality the journalist is attempting to convey. The inference of reality, however, is not always justified.
Photography is a language. 1 A part of our visual culture, photographs are used across society for diverse purposes ranging from personal remembrances to an international means of communication. Photos are used in scrapbooks and greeting cards, as backgrounds on computer desktops and decorations in our homes. Photographs 1 This thesis follows the style and format of History of Photography. surround us. From the moment one wakes up, to the moment one goes to sleep, the twenty?first century is defined by photographic images.
Numerous studies, starting from Amihud and Mendelson (1986) have shown that liquidity is an important variable that affects the stock prices. Using various measures of liquidity, these studies generally support the liquidity premium theory, which provides a rationale for a trade off between return on assets and their liquidity. In general, higher rate of returns are associated with less liquid assets.. For example, using bid-ask spread as a measure of liquidity, Amihud and Mendelson (1986) show that the quoted bid-ask spread has a significant positive effect on stock returns. Similarly, Eleswarapu and Reinganum (1993) using the same quoted bid-ask spread as a proxy for liquidity find that the positive relation documented in Amihud and Mendelson is restricted only in January.
Brennan and Subrahmanyam (1996) take an innovative approach by estimating the price impact of a trade based on Kyle’s (1985) model and find that it is significantly positively related to average returns. Easley, Hvidkjaer, and O’Hara (2002) document a similar result using their measure of illiquidity called the probability of information trading, which reflects the adverse selection cost arising from information asymmetry among traders. Additional evidence on positive illiquidity-return relation is provided by Chalmers and Kadlec (1998) using the amortized bid-ask spread, by Datar, Naik, and Radcliff (1998) using share turnover, by Brennan, Chordia, and Subrahmanyam (1998) using dollar trading volume, and most recently by Hasbrouck (2003) using a liquidity proxy based on a newly created effective spread in the daily data.
