The Strand magazine

Vol.13-#40# called also no. 73-#238#

Locating a strand of the Seattle Fault Zone in southeast Seattle, Washington through topographic analysis, borehole analysis and ground penetrating radar

Contributing to the evaluation of seismic hazards, a previously unmapped strand of the Seattle Fault Zone (SFZ), cutting across the southwest side of Lake Washington and southeast Seattle, is located and characterized on the basis of bathymetry, borehole logs, and ground penetrating radar (GPR). Previous geologic mapping and geophysical analysis of the Seattle area have generally mapped the locations of some strands of the SFZ, though a complete and accurate understanding of locations of all individual strands of the fault system is still incomplete. A bathymetric scarp-like feature and co-linear aeromagnetic anomaly lineament defined the extent of the study area. A 2-dimensional lithology cross-section was constructed using six boreholes, chosen from suitable boreholes in the study area. In addition, two GPR transects, oblique to the proposed fault trend, served to identify physical differences in subsurface materials. The proposed fault trace follows the previously mapped contact between the Oligocene Blakeley Formation and Quaternary deposits, and topographic changes in slope. GPR profiles in Seward Park and across the proposed fault location show the contact between the Blakeley Formation and unconsolidated glacial deposits, but it does not constrain an offset. However, north-dipping beds in the Blakely Formation are consistent with previous interpretations of P-wave seismic profiles on Mercer Island and Bellevue, Washington. The profiles show the mapped location of the aeromagnetic lineament in Lake Washington and the inferred location of the steeply-dipping, high-amplitude bedrock reflector, representing a fault strand. This north-dipping reflector is likely the same feature identified in my analysis. I characterize the strand as a splay fault, antithetic to the frontal fault of the SFZ. This new fault may pose a geologic hazard to the region.

Chain scission and branching in irradiated poly(tetrafluoroethylene-co-hexafluoropropylene)

The radiation chemistry of poly(tetrafluoroethylene-co-hexafluoropropylene) (FEP) with a TFE mole fraction of 0.90 has been studied under vacuum using Co-60 gamma-radiation over a range of temperatures and absorbed doses. The radiolysis temperatures were 300, 363, 423, 523 and 543 K. New structure formation in the copolymers was analysed by solid-state F-19 NMR spectroscopy. The new structures formed in the copolymers have been identified and the G-values for the formation of new chemical structures have been investigated at 363 and 523 K. These two temperatures are just above and just below the polymer T-g and T-m, respectively. At the lower temperature, there was no evidence for any chain branching and an estimate of G(S) of 1.0 was obtained. A value of G(S) of 1.3 and a minimum value of G(X)(Y) of 1.3 were obtained at 523 K. (C) 2003 Society of Chemical Industry.

The Mre11 complex and ATM: a two-way functional interaction in recognising and signaling DNA double strand breaks

Mutations in components of the Mre 11/Rad50/Nbs1 complex give rise to genetic disorders characterized by neurological abnormalities, radiosensitivity, cell cycle checkpoint defects, genomic instability and cancer predisposition. Evidence exists that this complex associates with chromatin during DNA replication and acts as a sensor of double strand breaks (dsbs) in DNA after exposure to radiation. A series of recent reports provides additional support that the complex senses breaks in DNA and relays this information to ATM, mutated in ataxia-telangiectasia (A-T), which in turn activates pathways for cell cycle checkpoint activation. Paradoxically members of the Mre11 complex are also downstream of ATM in these pathways. Here, Lavin attempts to make sense of this sensing mechanism with reference to a series of recent reports on the topic. (C) 2004 Elsevier B.V. All rights reserved.

Countering cooperative effects in protease inhibitors using constrained b-strand-mimicking templates in focused combinatorial libraries

A major problem in de novo design of enzyme inhibitors is the unpredictability of the induced fit, with the shape of both ligand and enzyme changing cooperatively and unpredictably in response to subtle structural changes within a ligand. We have investigated the possibility of dampening the induced fit by using a constrained template as a replacement for adjoining segments of a ligand. The template preorganizes the ligand structure, thereby organizing the local enzyme environment. To test this approach, we used templates consisting of constrained cyclic tripeptides, formed through side chain to main chain linkages, as structural mimics of the protease-bound extended beta-strand conformation of three adjoining amino acid residues at the N- or C-terminal sides of the scissile bond of substrates. The macrocyclic templates were derivatized to a range of 30 structurally diverse molecules via focused combinatorial variation of nonpeptidic appendages incorporating a hydroxyethylamine transition-state isostere. Most compounds in the library were potent inhibitors of the test protease (HIV-1 protease). Comparison of crystal structures for five protease-inhibitor complexes containing an N-terminal macrocycle and three protease-inhibitor complexes containing a C-terminal macrocycle establishes that the macrocycles fix their surrounding enzyme environment, thereby permitting independent variation of acyclic inhibitor components with only local disturbances to the protease. In this way, the location in the protease of various acyclic fragments on either side of the macrocyclic template can be accurately predicted. This type of templating strategy minimizes the problem of induced fit, reducing unpredictable cooperative effects in one inhibitor region caused by changes to adjacent enzyme-inhibitor interactions. This idea might be exploited in template-based approaches to inhibitors of other proteases, where a beta-strand mimetic is also required for recognition, and also other protein-binding ligands where different templates may be more appropriate.

Double-strand break repair gene polymorphisms and risk of breast or ovarian cancer

Deficiencies in DNA repair have been hypothesized to increase cancer risk and excess cancer incidence is a feature of inherited diseases caused by defects in DNA damage recognition and repair. We investigated, using a case-control design, whether the double-strand break repair gene polymorphisms RAD51 5' untranslated region -135 G > C, XRCC2 R188H G > A, and XRCC3 T241M C > T were associated with risk of breast or ovarian cancer in Australian women. Sample sets included 1,456 breast cancer cases and 793 age-matched controls ages under 60 years of age, 549 incident ovarian cancer cases, and 335 controls of similar age distribution. For the total sample and the subsample of Caucasian women, there were no significant differences in genotype distribution between breast cancer cases and controls or between ovarian cancer cases and combined control groups. The crude odds ratios (OR) and 95% confidence intervals (95% CI) associated with the RAD51 GC/CC genotype frequency was OR, 1.10; 95% CI, 0.80-1.41 for breast cancer and OR, 1.22; 95% CI, 0.92-1.62 for ovarian cancer. Similarly, there were no increased risks associated with the XRCC2 GA/AA genotype (OR, 0.98; 95% CI, 0.76-1.26 for breast cancer and OR, 0.93; 95% CI, 0.69-1.25 for ovarian cancer) or the XRCC3 CT/TT genotype (OR, 0.92; 95% Cl, 0.77-1.10 for breast cancer and OR, 0.87; 95% CI, 0.71-1.08 for ovarian cancer). Results were little changed after adjustment for age and other measured risk factors. Although there was little statistical power to detect modest increases in risk for the homozygote variant genotypes, particularly for the rare RAD51 and XRCC2 variants, the data suggest that none of these variants play a major role in the etiology of breast or ovarian cancer.

A strand of vermicelli:Dr Darwin's part in the creation of Frankenstein's monster

Although much has been written about Mary Shelley's Frankenstein, the part played by Erasmus Darwin (1731-1802) has been almost entirely neglected. This is odd as, apart from some ghost stories, Dr Darwin is the one influence mentioned in both the 1816 and 1831 prefaces to the book. The present contribution aims to redress that omission. It aims to show that Darwin's ideas about spontaneous generation, his anti-establishment ideas, and his literary genius played a significant role in forming the 'dark and shapeless substance' surging in Mary Shelley's mind during the summer of 1816 and from which her tale of Gothic horror emerged. It is, however, ultimately ironic that Frankenstein, which warns against a too enthusiastic use of scientific knowledge, should have been partly inspired by one of the most optimistically forward-looking of all late eighteenth-century thinkers. © 2007 Institute of Materials, Minerals and Mining.

Flexibility of short-strand RNA in aqueous solution as revealed by molecular dynamics simulation:are A′-RNA and A-RNA distinct conformational structures?

We use molecular dynamics simulations to compare the conformational structure and dynamics of a 21-base pair RNA sequence initially constructed according to the canonical A-RNA and A'-RNA forms in the presence of counterions and explicit water. Our study aims to add a dynamical perspective to the solid-state structural information that has been derived from X-ray data for these two characteristic forms of RNA. Analysis of the three main structural descriptors commonly used to differentiate between the two forms of RNA namely major groove width, inclination and the number of base pairs in a helical twist over a 30 ns simulation period reveals a flexible structure in aqueous solution with fluctuations in the values of these structural parameters encompassing the range between the two crystal forms and more. This provides evidence to suggest that the identification of distinct A-RNA and A'-RNA structures, while relevant in the crystalline form, may not be generally relevant in the context of RNA in the aqueous phase. The apparent structural flexibility observed in our simulations is likely to bear ramifications for the interactions of RNA with biological molecules (e.g. proteins) and non-biological molecules (e.g. non-viral gene delivery vectors). © CSIRO 2009.

β-Strand mimetic foldamers rigidified through dipolar repulsion

Many therapeutically relevant protein-protein interactions contain hot-spot regions on secondary structural elements, which contribute disproportionately to binding enthalpy. Mimicry of such α-helical regions has met with considerable success, however the analogous approach for the β-strand has received less attention. Presented herein is a foldamer for strand mimicry in which dipolar repulsion is a central determinant of conformation. Computation as well as solution- and solid-phase data are consistent with an ensemble weighted almost exclusively in favor of the desired conformation.

La scission des fermières : dissidence et autonomie, 1937-1950

Les Cercles de Fermières font partie intégrante de ma vie familiale. Ma mère, ma soeur, ma belle-soeur, trois de mes tantes ont été membres du cercle local de Ste-Agnès-de-Dundee, dont le membership oscillait constamment entre 15 et 18 membres. Le troisième jeudi du mois était « la sortie » de ma mère. Elle affirmait détester les journées d'études, les congrès, mais en faisait toujours partie. Les Cercles de Fermières constituent une des plus anciennes associations féminines au Québec et la première à regrouper autant de femmes. En 1915, elles sont 160 ; en 1919, au premier congrès elles sont 1 047; en 1940, 27 000; en 1944, 49 000 et en comptent plus de 80 000 membres. L'histoire de ce mouvement féminin rural ne manque donc pas d'intérêt pour l'histoire des femmes. Le sujet est d'autant plus attrayant qu'il recoupe l'histoire sociale et politique du Québec ainsi que l'histoire de l’Église. Le mouvement prend naissance en 1915 sous les auspices du ministère de l’Agriculture du Québec, stratégie utilisée principalement pour contrer l'exode rural. Les évêques, qui avaient d'abord approuvé et appuyé les Cercles de Fermières, deviennent, à partir de 1940, moins favorables à l'organisation. La neutralité du mouvement, le caractère facultatif de la présence d'un aumônier, les réformes apportées par le gouvernement Godbout, entre autres le droit de vote accordé aux femmes sans oublier la peur du communisme, alertent l'épiscopat québécois. Les évêques craignent aussi pour leur autorité. À l’heure où l'épiscopat désire regrouper l'ensemble de la population québécoise selon le modèle diocésain, les Cercles de Fermières adoptent la division par districts agronomiques proposée par l'État pour fédérer ses cercles. Comme un autre mouvement rural, l'Union Catholique des cultivateurs, fondée en 1924 et parrainée par l'épiscopat québécois, est regroupé selon les diocèses, on estime que ce modèle pourrait avantageusement remplacer la division agronomique. […]

STRUCTURAL ANALYSIS OF RIBOSOME BINDING ELEMENTS OF THE 3´ UTR IN TWO POSITIVE-STRAND PLANT RNA VIRUSES

Turnip crinkle virus (TCV) and Pea enation mosaic virus (PEMV) are two positive (+)-strand RNA viruses that are used to investigate the regulation of translation and replication due to their small size and simple genomes. Both viruses contain cap-independent translation elements (CITEs) within their 3´ untranslated regions (UTRs) that fold into tRNA-shaped structures (TSS) according to nuclear magnetic resonance and small angle x-ray scattering analysis (TCV) and computational prediction (PEMV). Specifically, the TCV TSS can directly associate with ribosomes and participates in RNA-dependent RNA polymerase (RdRp) binding. The PEMV kissing-loop TSS (kl-TSS) can simultaneously bind to ribosomes and associate with the 5´ UTR of the viral genome. Mutational analysis and chemical structure probing methods provide great insight into the function and secondary structure of the two 3´ CITEs. However, lack of 3-D structural information has limited our understanding of their functional dynamics. Here, I report the folding dynamics for the TCV TSS using optical tweezers (OT), a single molecule technique. My study of the unfolding/folding pathways for the TCV TSS has provided an unexpected unfolding pathway, confirmed the presence of Ψ3 and hairpin elements, and suggested an interconnection between the hairpins and pseudoknots. In addition, this study has demonstrated the importance of the adjacent upstream adenylate-rich sequence for the formation of H4a/Ψ3 along with the contribution of magnesium to the stability of the TCV TSS. In my second project, I report on the structural analysis of the PEMV kl-TSS using NMR and SAXS. This study has re-confirmed the base-pair pattern for the PEMV kl-TSS and the proposed interaction of the PEMV kl-TSS with its interacting partner, hairpin 5H2. The molecular envelope of the kl-TSS built from SAXS analysis suggests the kl-TSS has two functional conformations, one of which has a different shape from the previously predicted tRNA-shaped form. Along with applying biophysical methods to study the structural folding dynamics of RNAs, I have also developed a technique that improves the production of large quantities of recombinant RNAs in vivo for NMR study. In this project, I report using the wild-type and mutant E.coli strains to produce cost-effective, site-specific labeled, recombinant RNAs. This technique was validated with four representative RNAs of different sizes and complexity to produce milligram amounts of RNAs. The benefit of using site-specific labeled RNAs made from E.coli was demonstrated with several NMR techniques.

On The Consistency Of Monte Carlo Track Structure Dna Damage Simulations.

Monte Carlo track structures (MCTS) simulations have been recognized as useful tools for radiobiological modeling. However, the authors noticed several issues regarding the consistency of reported data. Therefore, in this work, they analyze the impact of various user defined parameters on simulated direct DNA damage yields. In addition, they draw attention to discrepancies in published literature in DNA strand break (SB) yields and selected methodologies. The MCTS code Geant4-DNA was used to compare radial dose profiles in a nanometer-scale region of interest (ROI) for photon sources of varying sizes and energies. Then, electron tracks of 0.28 keV-220 keV were superimposed on a geometric DNA model composed of 2.7 × 10(6) nucleosomes, and SBs were simulated according to four definitions based on energy deposits or energy transfers in DNA strand targets compared to a threshold energy ETH. The SB frequencies and complexities in nucleosomes as a function of incident electron energies were obtained. SBs were classified into higher order clusters such as single and double strand breaks (SSBs and DSBs) based on inter-SB distances and on the number of affected strands. Comparisons of different nonuniform dose distributions lacking charged particle equilibrium may lead to erroneous conclusions regarding the effect of energy on relative biological effectiveness. The energy transfer-based SB definitions give similar SB yields as the one based on energy deposit when ETH ≈ 10.79 eV, but deviate significantly for higher ETH values. Between 30 and 40 nucleosomes/Gy show at least one SB in the ROI. The number of nucleosomes that present a complex damage pattern of more than 2 SBs and the degree of complexity of the damage in these nucleosomes diminish as the incident electron energy increases. DNA damage classification into SSB and DSB is highly dependent on the definitions of these higher order structures and their implementations. The authors' show that, for the four studied models, different yields are expected by up to 54% for SSBs and by up to 32% for DSBs, as a function of the incident electrons energy and of the models being compared. MCTS simulations allow to compare direct DNA damage types and complexities induced by ionizing radiation. However, simulation results depend to a large degree on user-defined parameters, definitions, and algorithms such as: DNA model, dose distribution, SB definition, and the DNA damage clustering algorithm. These interdependencies should be well controlled during the simulations and explicitly reported when comparing results to experiments or calculations.

Photo-fenton degradation of poly(Ethyleneglycol)

Polyethyleneglycol (PEG) was photooxidized in a photo-Fenton system and results compared with the dark reaction. The products were analysed using GPC and HPLC. In the absence of light, PEG samples needed 490 min to reduce their w by 50%, whereas under UV irradiation, only 10 min were necessary. The exponential decay of w with a concomitant increase in polydispersity and number of average chain scission, characterized a random chain scission mechanism. The degradation products of PEG in both systems showed the presence of lower molecular weight products, including smaller ethyleneglycols and formic acid. The mechanism involves consecutive processes, were the larger ethyleneglycols give rise, successively, to smaller ones. This suggests that the mechanism involves successive scissions of the polymer chain. Irradiated samples decomposed faster than those kept in the dark This study proves that the foto-Fenton method associated with UV-light is a good reactant for PEG photodegradation.