Direct infusion mass spectrometry metabolomics dataset: a benchmark for data processing and quality control

Direct-infusion mass spectrometry (DIMS) metabolomics is an important approach for characterising molecular responses of organisms to disease, drugs and the environment. Increasingly large-scale metabolomics studies are being conducted, necessitating improvements in both bioanalytical and computational workflows to maintain data quality. This dataset represents a systematic evaluation of the reproducibility of a multi-batch DIMS metabolomics study of cardiac tissue extracts. It comprises of twenty biological samples (cow vs. sheep) that were analysed repeatedly, in 8 batches across 7 days, together with a concurrent set of quality control (QC) samples. Data are presented from each step of the workflow and are available in MetaboLights. The strength of the dataset is that intra- and inter-batch variation can be corrected using QC spectra and the quality of this correction assessed independently using the repeatedly-measured biological samples. Originally designed to test the efficacy of a batch-correction algorithm, it will enable others to evaluate novel data processing algorithms. Furthermore, this dataset serves as a benchmark for DIMS metabolomics, derived using best-practice workflows and rigorous quality assessment

High-precision epsilon expansions of single-mass-scale four-loop vacuum bubbles

In this article we present a high-precision evaluation of the expansions in \e=(4-d)/2 of (up to) four-loop scalar vacuum master integrals, using the method of difference equations developed by S. Laporta. We cover the complete set of `QED-type' master integrals, i.e. those with a single mass scale only (i.e. $m_i\in\{0,m\}$) and an even number of massive lines at each vertex. Furthermore, we collect all that is known analytically about four-loop `QED-type' masters, as well as about {\em all} single-mass-scale vacuum integrals at one-, two- and three-loop order.Comment: 25 pages, uses axodraw.st

Metabolomics reveals mouse plasma metabolite responses to acute exercise and effects of disrupting AMPK-glycogen interactions

Introduction: The AMP-activated protein kinase (AMPK) is a master regulator of energy homeostasis that becomes activated by exercise and binds glycogen, an important energy store required to meet exercise-induced energy demands. Disruption of AMPK-glycogen interactions in mice reduces exercise capacity and impairs whole-body metabolism. However, the mechanisms underlying these phenotypic effects at rest and following exercise are unknown. Furthermore, the plasma metabolite responses to an acute exercise challenge in mice remain largely uncharacterized. Methods: Plasma samples were collected from wild type (WT) and AMPK double knock-in (DKI) mice with disrupted AMPK-glycogen binding at rest and following 30-min submaximal treadmill running. An untargeted metabolomics approach was utilized to determine the breadth of plasma metabolite changes occurring in response to acute exercise and the effects of disrupting AMPK-glycogen binding. Results: Relative to WT mice, DKI mice had reduced maximal running speed (p < 0.0001) concomitant with increased body mass (p < 0.01) and adiposity (p < 0.001). A total of 83 plasma metabolites were identified/annotated, with 17 metabolites significantly different (p < 0.05; FDR<0.1) in exercised (↑6; ↓11) versus rested mice, including amino acids, acylcarnitines and steroid hormones. Pantothenic acid was reduced in DKI mice versus WT. Distinct plasma metabolite profiles were observed between the rest and exercise conditions and between WT and DKI mice at rest, while metabolite profiles of both genotypes converged following exercise. These differences in metabolite profiles were primarily explained by exercise-associated increases in acylcarnitines and steroid hormones as well as decreases in amino acids and derivatives following exercise. DKI plasma showed greater decreases in amino acids following exercise versus WT. Conclusion: This is the first study to map mouse plasma metabolomic changes following a bout of acute exercise in WT mice and the effects of disrupting AMPK-glycogen interactions in DKI mice. Untargeted metabolomics revealed alterations in metabolite profiles between rested and exercised mice in both genotypes, and between genotypes at rest. This study has uncovered known and previously unreported plasma metabolite responses to acute exercise in WT mice, as well as greater decreases in amino acids following exercise in DKI plasma. Reduced pantothenic acid levels may contribute to differences in fuel utilization in DKI mice

Two-loop corrections to the Isgur-Wise function in QCD sum rules

We complete the QCD sum rule analysis of the Isgur Wise form factor $\xi(v\cdot v')$ at next-to-leading order in renormalization-group improved perturbation theory. To this end, the exact result for the two-loop corrections to the perturbative contribution is derived using the heavy quark effective theory. Several techniques for the evaluation of two-loop integrals involving two different types of heavy quark propagators are discussed in detail, among them the methods of integration by parts and differential equations. The order-$\alpha_s$ corrections to the Isgur-Wise function turn out to be small and well under control. At large recoil, they tend to decrease the form factor by $5-10\%$.Comment: 24 pages (REVTEX), 2 figures available upon request, SLAC-PUB-599

A Heavy-Light Chiral Quark Model

We present a new chiral quark model for mesons involving a heavy and a light (anti-) quark. The model relates various combinations of a quark - meson coupling constant and loop integrals to physical quantities. Then, some quantities may be predicted and some used as input. The extension from other similar models is that the present model includes the lowest order gluon condensate of the order (300 MeV)^4 determined by the mass splitting of the 0^- and the 1^- heavy meson states. Within the model, we find a reasonable description of parameters such as the decay constants f_B and f_D, the Isgur-Wise function and the axial vector coupling g_A in chiral perturbation theory for light and heavy mesons.Comment: 31 pages, 13 figures, RevTex4.

A magic connection between massive and massless diagrams

A useful connection between two-loop massive vacuum integrals and one-loop off-shell triangle diagrams with massless internal particles is established for arbitrary values of the space-time dimension n.Comment: 11 pages, plain latex, 1 figure (in latex); ps file available by anonymous ftp at ftp://vsfys1.fi.uib.no/anonymous/pub/bergen95-07.p

Leptonic and Semileptonic Decays of Charm and Bottom Hadrons

We review the experimental measurements and theoretical descriptions of leptonic and semileptonic decays of particles containing a single heavy quark, either charm or bottom. Measurements of bottom semileptonic decays are used to determine the magnitudes of two fundamental parameters of the standard model, the Cabibbo-Kobayashi-Maskawa matrix elements $V_{cb}$ and $V_{ub}$. These parameters are connected with the physics of quark flavor and mass, and they have important implications for the breakdown of CP symmetry. To extract precise values of $|V_{cb}|$ and $|V_{ub}|$ from measurements, however, requires a good understanding of the decay dynamics. Measurements of both charm and bottom decay distributions provide information on the interactions governing these processes. The underlying weak transition in each case is relatively simple, but the strong interactions that bind the quarks into hadrons introduce complications. We also discuss new theoretical approaches, especially heavy-quark effective theory and lattice QCD, which are providing insights and predictions now being tested by experiment. An international effort at many laboratories will rapidly advance knowledge of this physics during the next decade.Comment: This review article will be published in Reviews of Modern Physics in the fall, 1995. This file contains only the abstract and the table of contents. The full 168-page document including 47 figures is available at http://charm.physics.ucsb.edu/papers/slrevtex.p

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy