Flood magnitude-frequency and lithologic control on bedrock river incision in post-orogenic terrain

Mixed bedrock-alluvial rivers - bedrock channels lined with a discontinuous alluvial cover - are key agents in the shaping of mountain belt topography by bedrock fluvial incision. Whereas much research focuses upon the erosional dynamics of such rivers in the context of rapidly uplifting orogenic landscapes, the present study investigates river incision processes in a post-orogenic (cratonic) landscape undergoing extremely low rates of incision (> 5 m/Ma). River incision processes are examined as a function of substrate lithology and the magnitude and frequency of formative flows along Sandy Creek gorge, a mixed bedrock-alluvial stream in arid SE-central Australia. Incision is focused along a bedrock channel with a partial alluvial cover arranged into riffle-pool macrobedforms that reflect interactions between rock structure and large-flood hydraulics. Variations in channel width and gradient determine longitudinal trends in mean shear stress (τb) and therefore also patterns of sediment transport and deposition. A steep and narrow, non-propagating knickzone (with 5% alluvial cover) coincides with a resistant quartzite unit that subdivides the gorge into three reaches according to different rock erodibility and channel morphology. The three reaches also separate distinct erosional styles: bedrock plucking (i.e. detachment-limited erosion) prevails along the knickzone, whereas along the upper and lower gorge rock incision is dependent upon large formative floods exceeding critical erosion thresholds (τc) for coarse boulder deposits that line 70% of the channel thalweg (i.e. transport-limited erosion). The mobility of coarse bed materials (up to 2 m diameter) during late Holocene palaeofloods of known magnitude and age is evaluated using step-backwater flow modelling in conjunction with two selective entrainment equations. A new approach for quantifying the formative flood magnitude in mixed bedrock-alluvial rivers is described here based on the mobility of a key coarse fraction of the bed materials; in this case the d84 size fraction. A 350 m3/s formative flood fully mobilises the coarse alluvial cover with τb200-300 N/m2 across the upper and lower gorge riffles, peaking over 500 N/m2 in the knickzone. Such floods have an annual exceedance probability much less than 10- 2 and possibly as low as 10- 3. The role of coarse alluvial cover in the gorge is discussed at two scales: (1) modulation of bedrock exposure at the reach-scale, coupled with adjustment to channel width and gradient, accommodates uniform incision across rocks of different erodibility in steady-state fashion; and (2) at the sub-reach scale where coarse boulder deposits (corresponding to <i>τ</i><sub>b</sub> minima) cap topographic convexities in the rock floor, thereby restricting bedrock incision to rare large floods. While recent studies postulate that decreasing uplift rates during post-orogenic topographic decay might drive a shift to transport-limited conditions in river networks, observations here and elsewhere in post-orogenic settings suggest, to the contrary, that extremely low erosion rates are maintained with substantial bedrock channel exposure. Although bed material mobility is known to be rate-limiting for bedrock river incision under low sediment flux conditions, exactly how a partial alluvial cover might be spatially distributed to either optimise or impede the rate of bedrock incision is open to speculation. Observations here suggest that the small volume of very stable bed materials lining Sandy Creek gorge is distributed so as to minimise the rate of bedrock fluvial incision over time

VARIETAL RESISTANCE

Production of all classes of wheat grown in the United States totaled 2.5 billion bushels in 1997. Common wheat, Triticum aestivum L. subsp. aestivum, is the primary source of all wheat varieties grown in the United States, with over 200 varieties known and over 100 varieties cultivated. These 100 varieties constitute over 95% of all wheat cultivated in the United States. Five general wheat classes are predominant in the United States: hard red winter, hard red spring, soft red winter, white, and durum

Structure-Based Design of Non-Natural Amino Acid Inhibitors of Amyloid Fibrillation

Many globular and natively disordered proteins can convert into amyloid fibers. These fibers are associated with numerous pathologies1 as well as with normal cellular functions2,3, and frequently form during protein denaturation4,5. Inhibitors of pathological amyloid fibers could serve as leads for therapeutics, provided the inhibitors were specific enough to avoid interfering with normal processes. Here we show that computer-aided, structure-based design can yield highly specific peptide inhibitors of amyloid formation. Using known atomic structures of segments of amyloid fibers as templates, we have designed and characterized an all D-amino acid inhibitor of fibrillation of the tau protein found in Alzheimer’s disease, and a non-natural L-amino acid inhibitor of an amyloid fiber that enhances sexual transmission of HIV. Our results indicate that peptides from structure-based designs can disrupt the fibrillation of full-length proteins, including those like tau that lack fully ordered native structures

Profiling of transcriptional and epigenetic changes during directed endothelial differentiation of human embryonic stem cells identifies FOXA2 as a marker of early mesoderm commitment

Introduction: Differentiation of vascular endothelial cells (ECs) in clinically relevant numbers for injection into ischaemic areas could offer therapeutic potential in the treatment of cardiovascular conditions, including myocardial infarction, peripheral vascular disease and stroke. While we and others have demonstrated successful generation of functional endothelial-like cells from human embryonic stem cells (hESCs), little is understood regarding the complex transcriptional and epigenetic changes that occur during differentiation, in particular during early commitment to a mesodermal lineage. Methods: We performed the first gene expression microarray study of hESCs undergoing directed differentiation to ECs using a monolayer-based, feeder-free and serum-free protocol. Microarray results were confirmed by quantitative RT-PCR and immunocytochemistry, and chromatin immunoprecipitation (ChIP)-PCR analysis was utilised to determine the bivalent status of differentially expressed genes. Results: We identified 22 transcription factors specific to early mesoderm commitment. Among these factors, FOXA2 was observed to be the most significantly differentially expressed at the hESC–EC day 2 timepoint. ChIP-PCR analysis revealed that the FOXA2 transcription start site is bivalently marked with histone modifications for both gene activation (H3K4me3) and repression (H3K27me3) in hESCs, suggesting the transcription factor may be a key regulator of hESC differentiation. Conclusion: This enhanced knowledge of the lineage commitment process will help improve the design of directed differentiation protocols, increasing the yield of endothelial-like cells for regenerative medicine therapies in cardiovascular disease

P. aeruginosa SGNH Hydrolase-Like Proteins AlgJ and AlgX Have Similar Topology but Separate and Distinct Roles in Alginate Acetylation

The O-acetylation of polysaccharides is a common modification used by pathogenic organisms to protect against external forces. Pseudomonas aeruginosa secretes the anionic, O-acetylated exopolysaccharide alginate during chronic infection in the lungs of cystic fibrosis patients to form the major constituent of a protective biofilm matrix. Four proteins have been implicated in the O-acetylation of alginate, AlgIJF and AlgX. To probe the biological function of AlgJ, we determined its structure to 1.83 Å resolution. AlgJ is a SGNH hydrolase-like protein, which while structurally similar to the N-terminal domain of AlgX exhibits a distinctly different electrostatic surface potential. Consistent with other SGNH hydrolases, we identified a conserved catalytic triad composed of D190, H192 and S288 and demonstrated that AlgJ exhibits acetylesterase activity in vitro. Residues in the AlgJ signature motifs were found to form an extensive network of interactions that are critical for O-acetylation of alginate in vivo. Using two different electrospray ionization mass spectrometry (ESI-MS) assays we compared the abilities of AlgJ and AlgX to bind and acetylate alginate. Binding studies using defined length polymannuronic acid revealed that AlgJ exhibits either weak or no detectable polymer binding while AlgX binds polymannuronic acid specifically in a length-dependent manner. Additionally, AlgX was capable of utilizing the surrogate acetyl-donor 4-nitrophenyl acetate to catalyze the O-acetylation of polymannuronic acid. Our results, combined with previously published in vivo data, suggest that the annotated O-acetyltransferases AlgJ and AlgX have separate and distinct roles in O-acetylation. Our refined model for alginate acetylation places AlgX as the terminal acetlytransferase and provides a rationale for the variability in the number of proteins required for polysaccharide O-acetylation

First radial velocity results from the MINiature Exoplanet Radial Velocity Array (MINERVA)

The MINiature Exoplanet Radial Velocity Array (MINERVA) is a dedicated observatory of four 0.7m robotic telescopes fiber-fed to a KiwiSpec spectrograph. The MINERVA mission is to discover super-Earths in the habitable zones of nearby stars. This can be accomplished with MINERVA's unique combination of high precision and high cadence over long time periods. In this work, we detail changes to the MINERVA facility that have occurred since our previous paper. We then describe MINERVA's robotic control software, the process by which we perform 1D spectral extraction, and our forward modeling Doppler pipeline. In the process of improving our forward modeling procedure, we found that our spectrograph's intrinsic instrumental profile is stable for at least nine months. Because of that, we characterized our instrumental profile with a time-independent, cubic spline function based on the profile in the cross dispersion direction, with which we achieved a radial velocity precision similar to using a conventional "sum-of-Gaussians" instrumental profile: 1.8 m s$^{-1}$ over 1.5 months on the RV standard star HD 122064. Therefore, we conclude that the instrumental profile need not be perfectly accurate as long as it is stable. In addition, we observed 51 Peg and our results are consistent with the literature, confirming our spectrograph and Doppler pipeline are producing accurate and precise radial velocities.Comment: 22 pages, 9 figures, submitted to PASP, Peer-Reviewed and Accepte

Temporal spatial and metabolic measures of walking in highly functional individuals with lower limb amputations

OBJECTIVE: The aim of this descriptive exploratory study is to record the temporal spatial parameters and metabolic energy expenditure during walking of individuals with amputation, walking with advanced prostheses and following completion of comprehensive rehabilitation, to able-bodied controls. DESIGN: Cross-sectional SETTING: Multi-disciplinary comprehensive rehabilitation centre PARTICIPANTS: Thirty severely injured United Kingdom military personnel with amputation and subsequent completion of their rehabilitation programme (10 unilateral trans-tibial, 10 unilateral trans-femoral, and 10 bilateral trans-femoral) were compared to (and of similar age, height and mass (p < 0.537) as) 10 able-bodied controls. INTERVENTIONS: Not applicable Main Outcomes and Measures: Temporal spatial and metabolic energy expenditure data were captured during walking on level ground at self-selected speed. RESULTS: The individuals with amputation were all male, with a mean age 29 years (SD = 4) and mean New Injury Severity Score of 31 (SD = 16). Walking speed, stride length, step length and cadence of individuals with a unilateral trans-tibial or trans-femoral amputation was comparable to controls, and only for individuals with a bilateral trans-femoral amputation was walking speed significantly slower (1·12m/s, p = 0.025) and cadence reduced (96 steps/min, p = 0.026). Oxygen cost for individuals with a unilateral trans-tibial amputation (0·15 ml/kg/m) was the same as for controls (0·15 ml/kg/m), and significantly increased by 20% (0·18ml/kg/m, p = 0.023) for unilateral trans-femoral and by 60% (0·24 ml/kg/m, p < 0.001) for bilateral trans-femoral individuals with amputation. CONCLUSION: The scientific literature reports a wide range of gait and metabolic energy expenditure across individuals with amputation. The results of this study indicate that the individuals with amputation have a gait pattern which is highly functional and efficient. This is comparable to a small number of studies reporting similar outcomes for individuals with a unilateral trans-tibial amputation, but the results from this study are better than those on individuals with trans-femoral amputations reported elsewhere, despite comparison with populations wearing similar prosthetic componentry. Those studies that do report similar outcomes have included individuals who have been provided with a comprehensive rehabilitation programme. This suggests that such a programme may be as important as, or even more important than, prosthetic component selection in improving metabolic energy expenditure. The data are made available as a benchmark for what is achievable in the rehabilitation of some individuals with amputations, but agreeably may not be possible for all amputees to achieve