Probing Light Atoms at Sub-nanometer Resolution: Realization of Scanning Transmission Electron Microscope Holography

Atomic resolution imaging in transmission electron microscopy (TEM) and scanning TEM (STEM) of light elements in electron-transparent materials has long been a challenge. Biomolecular materials, for example, are rapidly altered when illuminated with electrons. These issues have driven the development of TEM and STEM techniques that enable the structural analysis of electron beam-sensitive and weakly scattering nano-materials. Here, we demonstrate such a technique, STEM holography, capable of absolute phase and amplitude object wave measurement with respect to a vacuum reference wave. We use an amplitude-dividing nanofabricated grating to prepare multiple spatially separated electron diffraction probe beams focused at the sample plane, such that one beam transmits through the specimen while the others pass through vacuum. We raster-scan the diffracted probes over the region of interest. We configure the post specimen imaging system of the microscope to diffraction mode, overlapping the probes to form an interference pattern at the detector. Using a fast-readout, direct electron detector, we record and analyze the interference fringes at each position in a 2D raster scan to reconstruct the complex transfer function of the specimen, t(x). We apply this technique to image a standard target specimen consisting of gold nanoparticles on a thin amorphous carbon substrate, and demonstrate 2.4 angstrom resolution phase images. We find that STEM holography offers higher phase-contrast of the amorphous material while maintaining Au atomic lattice resolution when compared with high angle annular dark field STEM.Comment: 9 pages, 5 figures in main text, 1 supplemental figure in the appendi

Therapeutic Intervention for Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS): A Systematic Review and Meta-Analysis

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has been treated with several different interventions with limited success. This meta-analysis aims to review all trials reporting on therapeutic intervention for CP/CPPS using the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). Methods We searched Medline, PubMed, the Cochrane Pain, Palliative & Supportive Care Trials, the Cochrane Register of Controlled Trials, CINAHL, ClinicalTrials.gov, and the NIDDK website between 1947 and December 31, 2011 without language or study type restrictions. All RCTs for CP/CPPS lasting at least 6 weeks, with a minimum of 10 participants per arm, and using the NIH-CPSI score, the criterion standard for CP/CPPS, as an outcome measure were included. Data was extracted from each study by two independent reviewers. Gillbraith and I-squared plots were used for heterogeneity testing and Eggers and Peters methods for publication bias. Quality was assessed using a component approach and meta-regression was used to analyze sources of heterogeneity. Results: Mepartricin, percutaneous tibial nerve stimulation (PTNS), and triple therapy comprised of doxazosin + ibuprofen + thiocolchicoside (DIT) resulted in clinically and statistically significant reduction in NIH-CPSI total score. The same agents and aerobic exercise resulted in clinically and statistically significant NIH-CPSI pain domain score reduction. Acupuncture, DIT, and PTNS were found to produce statistically and clinically significant reductions in the NIH-CPSI voiding domain. A statistically significant placebo effect was found for all outcomes and time analysis showed that efficacy of all treatments increased over time. Alpha-blockers, antibiotics, and combinations of the two failed to show statistically or clinically significant NIH-CPSI reductions. Conclusion: Results from this meta-analysis reflect our current inability to effectively manage CP/CPPS. Clinicians and researchers must consider placebo effect and treatment efficacy over time and design studies creatively so we can more fully elucidate the etiology and role of therapeutic intervention in CP/CPPS.

Structured Electron Beam Illumination: A New Control Over the Electron Probe Weird Probes and New Experiments

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Bedrock erosion surfaces record former East Antarctic Ice Sheet extent

East Antarctica hosts large subglacial basins into which the East Antarctic Ice Sheet (EAIS) likely retreated during past warmer climates. However, the extent of retreat remains poorly constrained, making quantifying past and predicted future contributions to global sea level rise from these marine basins challenging. Geomorphological analysis and flexural modeling within the Wilkes Subglacial Basin is used to reconstruct the ice margin during warm intervals of the Oligocene–Miocene. Flat‐lying bedrock plateaus are indicative of an ice sheet margin positioned >400–500 km inland of the modern grounding zone for extended periods of the Oligocene–Miocene, equivalent to a 2 meter rise in global sea level. Our findings imply that if major EAIS retreat occurs in the future, isostatic rebound will enable the plateau surfaces to act as seeding points for extensive ice rises, thus limiting extensive ice margin retreat of the scale seen during the early EAIS

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Scoring docking conformations using predicted protein interfaces

BACKGROUND: Since proteins function by interacting with other molecules, analysis of protein-protein interactions is essential for comprehending biological processes. Whereas understanding of atomic interactions within a complex is especially useful for drug design, limitations of experimental techniques have restricted their practical use. Despite progress in docking predictions, there is still room for improvement. In this study, we contribute to this topic by proposing T-PioDock, a framework for detection of a native-like docked complex 3D structure. T-PioDock supports the identification of near-native conformations from 3D models that docking software produced by scoring those models using binding interfaces predicted by the interface predictor, Template based Protein Interface Prediction (T-PIP). RESULTS: First, exhaustive evaluation of interface predictors demonstrates that T-PIP, whose predictions are customised to target complexity, is a state-of-the-art method. Second, comparative study between T-PioDock and other state-of-the-art scoring methods establishes T-PioDock as the best performing approach. Moreover, there is good correlation between T-PioDock performance and quality of docking models, which suggests that progress in docking will lead to even better results at recognising near-native conformations. CONCLUSION: Accurate identification of near-native conformations remains a challenging task. Although availability of 3D complexes will benefit from template-based methods such as T-PioDock, we have identified specific limitations which need to be addressed. First, docking software are still not able to produce native like models for every target. Second, current interface predictors do not explicitly consider pairwise residue interactions between proteins and their interacting partners which leaves ambiguity when assessing quality of complex conformations