Estimating loop length from CryoEM images at medium resolutions

Background: De novo protein modeling approaches utilize 3-dimensional (3D) images derived from electron cryomicroscopy (CryoEM) experiments. The skeleton connecting two secondary structures such as α-helices represent the loop in the 3D image. The accuracy of the skeleton and of the detected secondary structures are critical in De novo modeling. It is important to measure the length along the skeleton accurately since the length can be used as a constraint in modeling the protein. Results: We have developed a novel computational geometric approach to derive a simplified curve in order to estimate the loop length along the skeleton. The method was tested using fifty simulated density images of helix-loop-helix segments of atomic structures and eighteen experimentally derived density data from Electron Microscopy Data Bank (EMDB). The test using simulated density maps shows that it is possible to estimate within 0.5 angstrom of the expected length for 48 of the 50 cases. The experiments, involving eighteen experimentally derived CryoEM images, show that twelve cases have error within 2 angstrom. Conclusions:The tests using both simulated and experimentally derived images show that it is possible for our proposed method to estimate the loop length along the skeleton if the secondary structure elements, such as α-helices, can be detected accurately, and there is a continuous skeleton linking the α-helices

Estimating Loop Length from CryoEM Images at Medium Resolutions

Background: De novo protein modeling approaches utilize 3-dimensional (3D) images derived from electron cryomicroscopy (CryoEM) experiments. The skeleton connecting two secondary structures such as α-helices represent the loop in the 3D image. The accuracy of the skeleton and of the detected secondary structures are critical in De novo modeling. It is important to measure the length along the skeleton accurately since the length can be used as a constraint in modeling the protein. Results: We have developed a novel computational geometric approach to derive a simplified curve in order to estimate the loop length along the skeleton. The method was tested using fifty simulated density images of helix-loop-helix segments of atomic structures and eighteen experimentally derived density data from Electron Microscopy Data Bank (EMDB). The test using simulated density maps shows that it is possible to estimate within 0.5 angstrom of the expected length for 48 of the 50 cases. The experiments, involving eighteen experimentally derived CryoEM images, show that twelve cases have error within 2 angstrom. Conclusions:The tests using both simulated and experimentally derived images show that it is possible for our proposed method to estimate the loop length along the skeleton if the secondary structure elements, such as α-helices, can be detected accurately, and there is a continuous skeleton linking the α-helices

E-government adoption: A cultural comparison

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ Springer Science + Business Media, LLC 2008.E-government diffusion is an international phenomenon. This study compares e-government adoption in the U.K. to adoption in the U.S. In particular, this study seeks to determine if the same factors are salient in both countries. Several studies have explored citizen acceptance of e-government services in the U.S. However, few studies have explored this phenomenon in the U.K. To identify the similarities and differences between the U.K. and the U.S. a survey is conducted in the U.K. and the findings are compared to the literature that investigates diffusion in the U.S. This study proposes a model of e-government adoption in the U.K. based on salient factors in the U.S. A survey is administered to 260 citizens in London to assess the importance of relative advantage, trust and the digital divide on intention to use e-government. The results of binary logistic regression indicate that there are cultural differences in e-government adoption in the U.K. and the U.S. The results indicate that of the prevailing adoption constructs, relative advantage and trust are pertinent in both the U.S. and the U.K., while ICT adoption barriers such as access and skill may vary by culture. Implications for research and practice are discussed

Attenuation of Age-Related Metabolic Dysfunction in Mice With a Targeted Disruption of the Cβ Subunit of Protein Kinase A

The cyclic adenosine monophosphate–dependent protein kinase A (PKA) pathway helps regulate both cell growth and division, and triglyceride storage and metabolism in response to nutrient status. Studies in yeast show that disruption of this pathway promotes longevity in a manner similar to caloric restriction. Because PKA is highly conserved, it can be studied in mammalian systems. This report describes the metabolic phenotype of mice lacking the PKA catalytic subunit Cβ. We confirmed that Cβ has high levels of expression in the brain but also showed moderate levels in liver. Cβ-null animals had reduced basal PKA activity while appearing overtly normal when fed standard rodent chow. However, the absence of Cβ protected mice from diet-induced obesity, steatosis, dyslipoproteinemia, and insulin resistance, without any differences in caloric intake or locomotor activity. These findings have relevant pharmacological implications because aging in mammals is characterized by metabolic decline associated with obesity, altered body fat distribution, and insulin resistance

The OSCE in a pre-registration osteopathy program: Introduction and psychometric properties

Objective To investigate the psychometric properties of the objective structured clinical examination (OSCE) conducted in the final year of a pre-professional osteopathy program. A variety of metrics are used to determine the reliability and validity of the examination. Methods Data from the OSCE conducted in 2011 was collated and analysed to establish the pass/fail rates, cost of the examination, internal consistency, and variance components. The examination was conducted over two days with students completing 5 stations on day 1 and 4 stations on day 2. Each station was of 15 min duration and there were 2 examiners per station. Results Forty-eight students and 31 examiners were involved in the examination. Twenty-six students failed at least one station with six students failing three or more stations. Cronbach's alpha was greater than 0.80 for all stations indicating that each is internally consistent and over 50% of the variance in the students' total score for a station was due to the students themselves. The total cost of conducting the examination was $AUD12,933.20. Conclusion The results of the study suggest that the OSCE format is an appropriate method for assessing clinical competency in osteopathic education. The OSCE should be used in conjunction with other forms of assessment to develop and overall picture of the students' clinical competency. Some modifications to the format of the assessment are required to improve the examination and these will be the subject of further studies

Subduction zone volcanic ash can fertilize the surface ocean and stimulate phytoplankton growth: Evidence from biogeochemical experiments and satellite data

Volcanoes confront Earth scientists with new fundamental questions: Can airborne volcanic ash release nutrients on contact with seawater, thereby excite the marine primary productivity (MPP); and, most notably, can volcanoes through oceanic fertilization affect the global climate in a way that is so far poorly understood? Here we present results from biogeochemical experiments showing that 1) volcanic ash from subduction zone volcanoes rapidly release an array of nutrients (co-)limiting algal growth in vast oceanic areas, 2) at a speed much faster (minute-scale) than hitherto known and that marine phytoplankton from low-iron oceanic areas can swiftly, within days, utilize iron from volcanic sources. We further present satellite data possibly indicating an increase of the MPP due to the seaward deposition of volcanic particulate matter. Our study supports the hypothesis that oceanic (iron) fertilization with volcanic ash may play a vital role for the development of the global climate