Evolution: Bacterial Mutation in Stationary Phase

AbstractA recent study indicates that the genomic mutation rate of the gut bacterium Escherichia coli is substantially higher in nongrowing than growing cultures. These findings are important in the light of the ongoing controversy over the generality and robustness of stationary phase mutagenesis and its evolutionary implications

Chemical-mechanical polishing: Enhancing the manufacturability of MEMS

The planarization technology of Chemical-Mechanical-Polishing (CMP), used for the manufacturing of multi-level metal interconnects for high-density Integrated Circuits (IC), is also readily adaptable as an enabling technology in Micro Electro Mechanical Systems (MEMS) fabrication, particularly polysilicon surface micromachining. CMP not only eases the design and manufacturability of MEMS devices by eliminating several photolithographic and film issues generated by severe topography, but also enables far greater flexibility with process complexity and associated designs. Thus, the CMP planarization technique alleviates processing problems associated with fabrication of multi-level polysilicon structures, eliminates design constraints linked with non-planar topography, and provides an avenue for integrating different process technologies. Examples of these enhancements include: an simpler extension of surface micromachining fabrication to multiple mechanical layers, a novel method of monolithic integration of electronics and MEMS, and a novel combination of bulk and surface micromachining

MEMS: A new approach to micro-optics

MicroElectroMechanical Systems (MEMS) and their fabrication technologies provide great opportunities for application to micro-optical systems (MOEMS). Implementing MOEMS technology ranges from simple, passive components to complicated, active systems. Here, an overview of polysilicon surface micromachining MEMS combined with optics is presented. Recent advancements to the technology, which may enhance its appeal for micro-optics applications are emphasized. Of all the MEMS fabrication technologies, polysilicon surface micromachining technology has the greatest basis in and leverages the most the infrastructure for silicon integrated circuit fabrication. In that respect, it provides the potential for very large volume, inexpensive production of MOEMS. This paper highlights polysilicon surface micromachining technology in regards to its capability to provide both passive and active mechanical elements with quality optical elements

Sustained Intraocular Pressure Elevation After Intravitreal Injection of Bevacizumab and Ranibizumab Associated with Trabeculitis

Anti-vascular endothelial growth factor agents are frequently used to treat a variety of ocular neovascular diseases. While agents like bevacizumab and ranibizumab appear to be safe and effective, there have been reports of severe intraocular inflammation as well as sustained elevation of intraocular pressure (IOP) after single or multiple intravitreal injections of these protein-based therapeutics. The true mechanism leading to inflammation and/or sustained spikes in IOP remains unknown. We report a patient with sustained IOP elevation and kerato-precipitates on the trabecular meshwork after multiple injections of both bevacizumab and ranibizumab. We propose that monomer antibodies, aggregated proteins, or other high molecular weight molecules might lead to inflammation in the trabecular meshwork and subsequent elevation in IOP

Multi-level polysilicon surface-micromachining technology: Applications and issues

Polysilicon surface micromachining is a technology for manufacturing Micro-Electro-Mechanical Systems (MEMS) which has, as its basis, the manufacturing methods and tool sets used to manufacture the integrated electronic circuit. This paper describes a three-level mechanical-polysilicon surface-micromachining technology and includes a discussion of the advantages of this level of process complexity along with issues which affect device fabrication and performance. Historically, the primary obstacles to multi-level polysilicon fabrication were related to the severe wafer topography generated by the repetition of film depositions and etching. The introduction of Chemical Mechanical Polishing (CMP) to surface micromachining has largely removed these issues and opened significant avenues for device complexity. Several examples of three-level devices with the benefits of CMP are presented. Of primary hindrance to the widespread use of polysilicon surface micromachining, and in particular microactuation mechanisms, are issues related to the device surfaces. The closing discussion examines the potential of several latter and post-fabrication processes to circumvent or to directly alleviate the surface problems

The Error and Repair Catastrophes: A Two-Dimensional Phase Diagram in the Quasispecies Model

This paper develops a two gene, single fitness peak model for determining the equilibrium distribution of genotypes in a unicellular population which is capable of genetic damage repair. The first gene, denoted by $\sigma_{via}$, yields a viable organism with first order growth rate constant $k > 1$ if it is equal to some target ``master'' sequence $\sigma_{via, 0}$. The second gene, denoted by $\sigma_{rep}$, yields an organism capable of genetic repair if it is equal to some target ``master'' sequence $\sigma_{rep, 0}$. This model is analytically solvable in the limit of infinite sequence length, and gives an equilibrium distribution which depends on \mu \equiv L\eps , the product of sequence length and per base pair replication error probability, and \eps_r , the probability of repair failure per base pair. The equilibrium distribution is shown to exist in one of three possible ``phases.'' In the first phase, the population is localized about the viability and repairing master sequences. As \eps_r exceeds the fraction of deleterious mutations, the population undergoes a ``repair'' catastrophe, in which the equilibrium distribution is still localized about the viability master sequence, but is spread ergodically over the sequence subspace defined by the repair gene. Below the repair catastrophe, the distribution undergoes the error catastrophe when $\mu$ exceeds \ln k/\eps_r , while above the repair catastrophe, the distribution undergoes the error catastrophe when $\mu$ exceeds $\ln k/f_{del}$, where $f_{del}$ denotes the fraction of deleterious mutations.Comment: 14 pages, 3 figures. Submitted to Physical Review

Manufacturing microsystems-on-a-chip with 5-level surface micromachining technology

An agile microsystem manufacturing technology has been developed that provides unprecedented 5 levels of independent polysilicon surface-micromachine films for the designer. Typical surface-micromachining processes offer a maximum of 3 levels, making this the most complex surface-micromachining process technology developed to date. Leveraged from the extensive infrastructure present in the microelectronics industry, the manufacturing method of polysilicon surface-micromachining offers similar advantages of high-volume, high-reliability, and batch-fabrication to microelectromechanical systems (MEMS) as has been accomplished with integrated circuits (ICs). These systems, comprised of microscopic-sized mechanical elements, are laying the foundation for a rapidly expanding, multi-billion dollar industry 2 which impacts the automotive, consumer product, and medical industries to name only a few

Population genetic variation in gene expression is associated with phenotypic variation in Saccharomyces cerevisiae

BACKGROUND: The relationship between genetic variation in gene expression and phenotypic variation observable in nature is not well understood. Identifying how many phenotypes are associated with differences in gene expression and how many gene-expression differences are associated with a phenotype is important to understanding the molecular basis and evolution of complex traits. RESULTS: We compared levels of gene expression among nine natural isolates of Saccharomyces cerevisiae grown either in the presence or absence of copper sulfate. Of the nine strains, two show a reduced growth rate and two others are rust colored in the presence of copper sulfate. We identified 633 genes that show significant differences in expression among strains. Of these genes, 20 were correlated with resistance to copper sulfate and 24 were correlated with rust coloration. The function of these genes in combination with their expression pattern suggests the presence of both correlative and causative expression differences. But the majority of differentially expressed genes were not correlated with either phenotype and showed the same expression pattern both in the presence and absence of copper sulfate. To determine whether these expression differences may contribute to phenotypic variation under other environmental conditions, we examined one phenotype, freeze tolerance, predicted by the differential expression of the aquaporin gene AQY2. We found freeze tolerance is associated with the expression of AQY2. CONCLUSIONS: Gene expression differences provide substantial insight into the molecular basis of naturally occurring traits and can be used to predict environment dependent phenotypic variation