Sarbanes Oxley: Is there a quantifiable difference?

Michelle Morris's poster on the ramifications of the Sarbanes Oxley Act

Structure and function of the mammalian small heat shock protein Hsp25

Hsp25 is the murine equivalent of human Hsp27, both of which are members of the small heat shock protein (sHsp) family. sHsps are a group of intracellular molecular chaperones that protect unstable intermediates of cellular proteins from aggregation and precipitation. Hsp27 and other sHsps play a role in various neurodegenerative diseases such as Alzheimer\u27s, Alexander\u27s, Creutzfeld-Jakob and Parkinson\u27s diseases. Crystallisation of mammalian sHsps has thus far not been achieved due to the polydisperse and dynamic nature of these proteins. As a result, the oligomeric structure of sHsps is unclear, hindering the elucidation of the functional mechanisms of these proteins. In this study, a series of site-directed Hsp25 mutants was constructed, in which polar residues of the flexible region of the C-terminal extension were replaced with less polar residues. The C-terminal extension of sHsps is typically short and unstructured and is thought to play an important role in solubilising these proteins and the complexes they form with target proteins by counteracting the hydrophobicity of the remainder of the sHsp. The C-terminal extension is also implicated in interaction with target proteins. Wildtype Hsp25 and various C-terminal extension mutants (E190A, R192A, Q194A, E199A, E204A, Q205A, K209L) were expressed and successfully purified. A truncation mutant, E190stop, was also constructed but became insoluble during the purification process, demonstrating the importance of the C-terminal extension in maintaining the stability of Hsp25. Wildtype and mutant Hsp25 proteins were characterised structurally and functionally using a range of spectroscopic techniques, including far-UV circular dichroism spectroscopy, tryptophan and ANS binding fluorescence spectroscopy, sizeexclusion fast protein liquid chromatography, nuclear magnetic resonance spectroscopy and chaperone assays under both reduction and heat stress conditions. These experiments enabled the identification of residues key to the chaperone ability of Hsp25. The R192A and Q194A mutants were functionally indistinct from the wildtype protein and exhibited only minor alterations to their structure. It was therefore concluded that the R192 and Q194 residues are not vital for Hsp25 to function as a molecular chaperone. Each of the glutamic acid residue mutants exhibited significant alterations in tertiary structure, with increases in exposure of hydrophobic regions compared with wildtype Hsp25, and a minor decrease in the oligomeric size of the E190A mutant was observed. Functionally, these mutants showed poor thermostability and disrupted chaperone function. Glutamic acid residues are abundantly present in proteins from thermophilic organisms and are implicated in the stability of these proteins at high temperatures. Replacement of each of the glutamic acid residues in the C-terminal extension of Hsp25 resulted in loss of solubility at elevated temperatures, indicating that these residues perform similar roles in both Hsp25 and thermophilic proteins. The increase in surface hydrophobicity may have contributed to the poor thermostability of these mutants and also the inefficient capture of target proteins observed in the chaperone assays. The tertiary and quaternary structures of the Q205A mutant were significantly perturbed and the function of this mutant was completely abolished under heat stress conditions. Alterations to the tertiary structure of the N-terminal domain were observed and oligomerisation was severely disrupted, with three distinct oligomeric forms being present: an oligomer larger than that of the wildtype protein and two smaller oligomers. The chaperone activity of this mutant was comparable to that of wildtype Hsp25 under reduction stress conditions, indicating that each of the oligomeric forms were functional. Under heat stress conditions, however, the Q205A mutant co-precipitated along with the target proteins. Flexibility of the mutated residue was considerably decreased, as assessed by NMR experiments, but the remainder of the C-terminal extension was not significantly altered. Together, these results lead to the conclusion that the Q205 residue is vital for the performance of Hsp25 as a molecular chaperone at elevated temperatures. Mutation of the K209 residue also showed disruption to the oligomerisation of Hsp25, with the K209L mutant eluting as three peaks after size-exclusion chromatography. This mutant was functionally defective under reduction stress conditions but showed comparable chaperone activity to the wildtype at high temperature, suggesting that the smaller oligomeric species require temperature-induced structural alterations in order to acquire chaperone ability. Because full chaperone activity was observed under reduction stress conditions, direct interactions between the C- terminal lysine residue of Hsp25 and target proteins is unlikely to be a requirement of chaperone activity. The stabilisation of αB-crystallin by αA-crystallin is important for the maintenance of the structure and function of αB-crystallin in the eye lens, where these sHsps are present in a ~3:1 ratio. Outside the eye lens, however, αA-crystallin is found only in trace amounts in some tissues. Co-complexes between various sHsps have been observed in vivo, for example between αB-crystallin and Hsp27, and it has been proposed that one or more ubiquitous sHsps stabilise αB-crystallin in non-lenticular tissues. Whilst αB-crystallin was found to be unstable above ~69ºC, Hsp25 remained almost completely in solution at 100ºC. A 3:1 Hsp25:αB-crystallin mixture showed practically identical thermostability to the Hsp25 homo-oligomer and provides support for the role of this sHsp as a stabiliser of αB-crystallin. Chaperone activity assays of the 3:1 mixture show results closely resembling those of the Hsp25 homooligomer and demonstrate that interactions between the two sHsps result in an altered chaperone activity of αB-crystallin. Significant insights into the structure and function of Hsp25 were gained in this study. Several residues in the C-terminal extension were identified as critical to the structural and functional integrity of this sHsp and analysis of the amino acid composition of the C-terminal extensions of sHsps from various organisms indicate that some of these residues may play similar roles in other sHsps

Meeting the Earthworks Builders: A flash-based video game

We propose to create a video game about Earthwork Builder Culture for school-age children in grades 4 through 8. In the past, the Earthwork Builder Culture has been poorly addressed in student learning materials. Current understanding and portrayal of American Indians remains largely stereotypical. This game will be developed using content generated by scientists, academics, educators, and American Indians. This approach will ensure that the native voice will be incorporated into the subject content areas, interface, game mechanics and artwork. Educational video games are a multimodal form of student engagement using visual images, animation, sound, text, and navigation/ interface design elements that engage students and allow them to make decisions and choices, developing problem solving skills and systems thinking. This medium will allow us to communicate profound aspects of American Indian thought through player interaction and the juxtaposition of graphical information

Evaluation of alternatives for trichlorotrifluoroethane (CFC-113) to clean and verify liquid oxygen systems

NASA Langley Research Center (LARC) investigated several alternatives to the use of tri-chloro-tri-fluoroethane(CFC-113) in oxygen cleaning and verification. Alternatives investigated include several replacement solvents, Non-Destructive Evaluation (NDE) and Total Organic Carbon (TOC) analysis. Among the solvents, 1, 1-dichloro-1-fluoroethane (HCFC 141b) and di-chloro-penta-fluoro-propane (HCFC 225) are the most suitable alternatives for cleaning and verification. However, use of HCFC 141b is restricted, HCFC 225 introduces toxicity hazards, and the NDE and TOC methods of verification are not suitable for processes at LaRC. Therefore, the interim recommendation is to sparingly use CFC-113 for the very difficult cleaning tasks where safety is critical and to use HCFC 225 to clean components in a controlled laboratory environment. Meanwhile, evaluation must continue on now solvents and procedures to find one suited to LaRCs oxygen cleaning needs

LG MS 11 Northern Lambda Nord Archives Finding Aid

Description: One of the earliest gay and lesbian groups in the state, NLN began in 1979 as a support network for the rural LGBT community, located in Aroostook County, with members in Maine and New Brunswick. By the mid-1980s, NLN had added an outreach component, working to educate the local community on LGBT identity and acceptance and health and HIV/AIDS issues. They also started a Gay-Lesbian Phoneline which grew into the Maine HIV/AIDS Hotline. The group disbanded in 2000, but re-formed in 2006. The Archives contains an extensive collection of organizational records, promotional materials, photo albums and artifacts. Date Range: 1977-2002 Size of Collection: 21 ft

Memory functioning in children with reading disabilities and/or attention deficit/hyperactivity disorder: a clinical investigation of their working memory and long-term memory functioning.

We examined memory functioning in children with reading disabilities (RD), Attention deficit/hyperactivity disorder (ADHD), and RD/ADHD using a clinic sample with a clinical instrument: the Children\u27s Memory Scale, enhancing its generalizability. Participants included 23 children with RD, 30 with ADHD, 30 with RD/ADHD, and 30 controls. Children with RD presented with reduced verbal short-term memory (STM) but intact visual STM, central executive (CE), and long-term memory (LTM) functioning. Their deficit in STM appeared specific to tasks requiring phonetic coding of material. Children with ADHD displayed intact CE and LTM functioning but reduced visual-spatial STM, especially when off stimulant medication. Children with RD/ADHD had deficits consistent with both disorders

Dose Dependent Effects of Caffeine on Cognitive Performance and Neuronal Activation

Many students assume that the more caffeine you drink, the better your cognitive performance. Over-consumption of caffeine has many negative effects, so if there are no dose related cognitive benefits to large amounts of caffeine, then college students should limit their intake. This study looked at whether ingesting a medium dose (200 mg) versus a lower dose (100 mg) of caffeine improved short term memory as measured by Flanker and n-back tests, compared to a control group. In addition, we looked at whether larger doses of caffeine produced a difference in neuronal activation during these tests as measured by functional near-infrared spectroscopy (fNIR). There were no differences in cognitive performance observed between the treatment groups, although the 200 mg caffeine group did have significantly more neuronal activation during higher cognitive load tasks. If increased neuronal activation does not correlate to increased performance, it may not reflect an actual benefit of increased caffeine consumption

The Strong Symmetric Genus Spectrum of Abelian Groups

The strong symmetric genus of a group G is the minimum genus of any compact surface on which G acts faithfully while preserving orientation. We investigate the set of positive integers which occur as the strong symmetric genus of a finite abelian group. This is called the strong symmetric genus spectrum. We prove that there are an infinite number of gaps in the strong symmetric genus spectrum of finite abelian groups. We also determine an upper bound for the size of a finite abelian group that can act faithfully on a surface of a particular genus and then find the genus of abelian groups in particular families. These formulas produce a lower bound for the density of the strong symmetric genus spectrum