The Role of Cadmium and Nickel in Estrogen Receptor Signaling and Breast Cancer: Metalloestrogens or Not?

During the last half-century, incidences of breast cancer have increased globally. Various factors —genetic and environmental— have been implicated in the initiation and progression of this disease. One potential environmental risk factor that has not received a lot of attention is the exposure to heavy metals. While several mechanisms have been put forth describing how high concentrations of heavy metals play a role in carcinogenesis, it is unclear whether chronic, lowlevel exposure to certain heavy metals (i.e. cadmium and nickel), can directly result in the development and progression of cancer. Cadmium and nickel have been hypothesized to play a role in breast cancer development by acting as metalloestrogens— metals that bind to estrogen receptors and mimic the actions of estrogen. Since the lifetime exposure to estrogen is a wellestablished risk factor for breast cancer, anything that mimics its activity will likely contribute to the etiology of the disease. However, heavy metals, depending on their concentration, are capable of binding to a variety of proteins and may exert their toxicities by disrupting multiple cellular functions, complicating the analysis of whether heavy metal-induced carcinogenesis is mediated by the estrogen receptor. The purpose of this review is to discuss the various epidemiological, in vivo, and in vitro studies that show a link between the heavy metals, cadmium and nickel, and breast cancer development. We will particularly focus on the studies that test whether or not these two metals act as metalloestrogens in order to assess the strength of the data supporting this hypothesis

Initial sequencing and analysis of the human genome

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62798/1/409860a0.pd

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Low-Backlash Worm Gears with NiTi Shape Memory Alloys

This paper investigates the use of martensitic Nickel-Titanium within worm gear transmissions in order to reduce the backlash of the gearwheels. In drive technology low-backlash transmissions are demanded. The backlash, adjusted at room temperature, decreases with increasing temperature as a consequence of different thermal expansions of the gear wheels and the housing. This can result in clamping of the teeth and leads to failure of the whole transmission. With NiTi-actuators, working in the extrinsic two-way effect, it is possible to realize two conditions of low-backlash and to avoid clamping of the gear wheels. The actuators induce a radial movement of the worm wheel depending on the increasing temperature within the gearbox. The decreasing backlash, as a result of different thermal expansions, is compensated by the expansion of the martensitic NiTi actuators while transforming to the austenite. The adjustment travel of the actuators has to correspond to the thermal change of the centre distance. By measuring the change of backlash on the test bench, the theoretical dimensioning of the actuator system can be verified. The variation of the main parameters like torque, the speed and different temperature levels as a result of the input power should demonstrate the effectiveness of the NiTi actuators