SHIFTX2: significantly improved protein chemical shift prediction

A new computer program, called SHIFTX2, is described which is capable of rapidly and accurately calculating diamagnetic 1H, 13C and 15N chemical shifts from protein coordinate data. Compared to its predecessor (SHIFTX) and to other existing protein chemical shift prediction programs, SHIFTX2 is substantially more accurate (up to 26% better by correlation coefficient with an RMS error that is up to 3.3× smaller) than the next best performing program. It also provides significantly more coverage (up to 10% more), is significantly faster (up to 8.5×) and capable of calculating a wider variety of backbone and side chain chemical shifts (up to 6×) than many other shift predictors. In particular, SHIFTX2 is able to attain correlation coefficients between experimentally observed and predicted backbone chemical shifts of 0.9800 (15N), 0.9959 (13Cα), 0.9992 (13Cβ), 0.9676 (13C′), 0.9714 (1HN), 0.9744 (1Hα) and RMS errors of 1.1169, 0.4412, 0.5163, 0.5330, 0.1711, and 0.1231 ppm, respectively. The correlation between SHIFTX2’s predicted and observed side chain chemical shifts is 0.9787 (13C) and 0.9482 (1H) with RMS errors of 0.9754 and 0.1723 ppm, respectively. SHIFTX2 is able to achieve such a high level of accuracy by using a large, high quality database of training proteins (>190), by utilizing advanced machine learning techniques, by incorporating many more features (χ2 and χ3 angles, solvent accessibility, H-bond geometry, pH, temperature), and by combining sequence-based with structure-based chemical shift prediction techniques. With this substantial improvement in accuracy we believe that SHIFTX2 will open the door to many long-anticipated applications of chemical shift prediction to protein structure determination, refinement and validation. SHIFTX2 is available both as a standalone program and as a web server (http://www.shiftx2.ca)

The reactions of the molecular nitrogen doubly charged ion with neutral molecules of relevance to planetary ionospheres

Diatomic dications (e.g. C02+) have been known to exist for several decades and are believed to be important components of energised media. Molecular dications possess significant internal energy due to the Coulombic repulsion of their two positive charges, meaning that many possible reaction channels are available to dications in a collision with a neutral molecule. Modellers have recently predicted that N22+ is present in the ionosphere of Earth and Titan as well as the dications C>22+ and 02+ in the ionosphere of Earth and CC>22+ in the ionosphere of Mars. These recent predictions, of dications in planetary ionospheres, imply that dications, and processes involving dication-neutral collisions, may have more significance than previously thought in the upper atmospheres of planets. Therefore this thesis describes a study of the reactions between N2 dications and neutrals, potentially of relevance to the ionosphere of Earth and Titan. A position sensitive coincidence (PSCO) time-of flight (TOF) mass spectrometer is used to probe the reactivity, energetics and dynamics of the bimolecular reactions of N22 . Dication-neutrals reactions often result in a pair of singly charged ions. The PSCO experiment is used to collect these pairs of singly-charged ions in coincidence. From the position-sensitive data we extract the velocity vectors of the product ions, and if the reaction of interest involves the formation of a third, undetected, neutral species, its velocity can be determined via conservation of momentum. The electron transfer reactions between dications and neutrals have been well rationalized 2+ previously, so only the electron transfer reactions of N2 with Ne and NO are discussed in this thesis. This thesis concentrates on probing the less well rationalized, bond- forming reactions between dications and neutrals. The bond-forming reactions of N22+ with O2, CO2, H2O, C2H2, CH4, H2 and Ar have been investigated and discussed. Several new bond-forming reactions mechanisms are derived for example, the bond-forming reactions of N22+ with O2 proceed via a 'long' lived complex which dissociates via loss of a neutral and then charge separation, a mechanism which is also operating for one of the bond-forming reactions of N2 with CO2 and N2 with H2O. Additional bond-forming reactions are detected for N22+ with CO2 and H2O, which proceed via shorter lived collision complexes. The reactions of N22+ with C2H2, CH4, H2 and Ar all proceed via a variety of mechanisms involving short-lived collision complexes or H and electron stripping

Analisis Penerapan Sistem Akuntansi Penjualan Kredit Dan Penerimaan Kas Dalam Mendukung Pengendalian Intern Perusahaan (Studi Kasus PT. Smart Tbk Refinery Surabaya)

System of selling credit accounting and system of cash receiving from account receivable is the source of life to achieving company goals. This research on the system of credit sales and cash receipts to support the company internal control. This research was conducted at PT. SMART Tbk Refinery Surabaya. PT. SMART Tbk Refinery Surabaya only selling cooking oil in the form of branded product and trading product on credit. PT. SMART Tbk Refinery Surabaya still has any weakness on system of selling credit accounting and system of cash receiving from account receivable, some of the sales transaction activity that occurred less supportive of the company\u27s internal control. This study aims to provide information to companies about the advantages and weakness of credit sales accounting system and cash receipts that have been applied by the company

Can Obesity Cause Depression? A Pseudo-panel Analysis

Objectives The US ranks ninth in obesity in the world, and approximately 7% of US adults experience major depressive disorder. Social isolation due to the stigma attached to obesity might trigger depression. Methods This paper examined the impact of obesity on depression. To overcome the endogeneity problem, we constructed pseudopanel data using the Behavioral Risk Factor Surveillance System from 1997 to 2008. Results The results were robust, and body mass index (BMI) was found to have a positive effect on depression days and the percentage of depressed individuals in the population. Conclusions We attempted to overcome the endogeneity problem by using a pseudo-panel approach and found that increases in the BMI increased depression days (or being depressed) to a statistically significant extent, with a large effect size

Assessing the performance of genome-wide association studies for predicting disease risk.

To date more than 3700 genome-wide association studies (GWAS) have been published that look at the genetic contributions of single nucleotide polymorphisms (SNPs) to human conditions or human phenotypes. Through these studies many highly significant SNPs have been identified for hundreds of diseases or medical conditions. However, the extent to which GWAS-identified SNPs or combinations of SNP biomarkers can predict disease risk is not well known. One of the most commonly used approaches to assess the performance of predictive biomarkers is to determine the area under the receiver-operator characteristic curve (AUROC). We have developed an R package called G-WIZ to generate ROC curves and calculate the AUROC using summary-level GWAS data. We first tested the performance of G-WIZ by using AUROC values derived from patient-level SNP data, as well as literature-reported AUROC values. We found that G-WIZ predicts the AUROC with 0.75). On the other hand, the average GWA study produces a multi-SNP risk predictor with an AUROC of 0.55. Detailed AUROC comparisons indicate that most SNP-derived risk predictions are not as good as clinically based disease risk predictors. All our calculations (ROC curves, AUROCs, explained heritability) are in a publicly accessible database called GWAS-ROCS (http://gwasrocs.ca). The G-WIZ code is freely available for download at https://github.com/jonaspatronjp/GWIZ-Rscript/

Modelling the role of tissue heterogeneity in epileptic rhythms

Epileptic seizure activity manifests as complex spatio-temporal dynamics on the clinically relevant macroscopic scale. These dynamics are known to arise from spatially heterogeneous tissue, but the relationship between specific spatial abnormalities and epileptic rhythm generation is not well understood. We formulate a simplified macroscopic modelling framework with which to study the role of spatial heterogeneity in the generation of epileptiform spatio-temporal rhythms. We characterize the overall model dynamics in terms of spontaneous activity and excitability and demonstrate normal and abnormal spreading of activity. We introduce a means to systematically investigate the topology of abnormal sub-networks and explore its impact on spontaneous and stimulus-evoked rhythmic dynamics. This computationally efficient framework complements results from detailed biophysical models, and allows the testing of specific hypotheses about epileptic dynamics on the macroscopic scale

Additional file 5: of Metabolome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants

Two-dimensional principal component analysis (PCA) of metabolite quantities obtained using LC/DFI-MS/MS-based profiling. Results are presented as scores (A) and loadings (B) plots. The percent variance accounted for by each principal component (PC) is indicated. For the scores plot, each dot represents a one of four replicates analyzed per plant species. Areas enclosed by 95 % confidence ellipses, containing dots of the same color, define statistically significant class separations [34]. Species abbreviations are defined in Table 1. Loadings representing individual metabolites are shown as black dots (B). Metabolites are indicated for select loadings. A complete listing of loadings data is found in Additional file 16. Abbreviations: C, acylcarnitine; SM, sphingomyelin; PC, phosphatidylcholine; aa, diacyl; ae, acyl-ester. A complete listing of full compound names and abbreviations is available online: http://www.biocrates.com/products/research-products/absoluteidq-p150-kit . (PDF 1591 kb