A Bayesian model selection approach to mediation analysis.

Genetic studies often seek to establish a causal chain of events originating from genetic variation through to molecular and clinical phenotypes. When multiple phenotypes share a common genetic association, one phenotype may act as an intermediate for the genetic effects on the other. Alternatively, the phenotypes may be causally unrelated but share genetic loci. Mediation analysis represents a class of causal inference approaches used to determine which of these scenarios is most plausible. We have developed a general approach to mediation analysis based on Bayesian model selection and have implemented it in an R package, bmediatR. Bayesian model selection provides a flexible framework that can be tailored to different analyses. Our approach can incorporate prior information about the likelihood of models and the strength of causal effects. It can also accommodate multiple genetic variants or multi-state haplotypes. Our approach reports posterior probabilities that can be useful in interpreting uncertainty among competing models. We compared bmediatR with other popular methods, including the Sobel test, Mendelian randomization, and Bayesian network analysis using simulated data. We found that bmediatR performed as well or better than these alternatives in most scenarios. We applied bmediatR to proteome data from Diversity Outbred (DO) mice, a multi-parent population, and demonstrate the power of mediation with multi-state haplotypes. We also applied bmediatR to data from human cell lines to identify transcripts that are mediated through or are expressed independently from local chromatin accessibility. We demonstrate that Bayesian model selection provides a powerful and versatile approach to identify causal relationships in genetic studies using model organism or human data

Crystal structure of 1-{(Z)-[(2E)-3-(4-chlorophenyl)-1-phenylprop-2-en-1-ylidene]amino}-3-ethylthiourea

In the title thiosemicarbazone compound, C18H18ClN3S, the CN3S residue is almost planar (r.m.s. deviation = 0.0031 Å) and forms dihedral angles of 65.99 (7) and 34.60 (10)° with the phenyl and chlorobenzene rings, respectively; the dihedral angle between the aromatic rings is 85.13 (8)°. The conformation about the C=N bond is Z, and that about the C=C bonds is E. The imine N and ethyl N atoms are syn and are linked by an ethyl–imine N—H...N hydrogen bond. This H atom also forms an intermolecular hydrogen bond to the thione S atom, resulting in a supramolecular helical chain propagating along the b axis. The chains are consolidated into a three-dimensional architecture by phenyl-C—H...Cl contacts and weak π–π interactions between centrosymmetrically related chlorobenzene rings [inter-centroid distance = 3.9127 (15) Å]

In-flight estimation of gyro noise on the Upper Atmosphere Research Satellite (UARS) and Extreme Ultraviolet Explorer (EUVE) missions

This paper characterizes the low-frequency noise response of the Teledyne dry rotor inertial reference unit (DRIRU) gyroscopes on the Upper Atmosphere Research Satellite (UARS) and the Extreme Ultraviolet Explorer (EUVE). The accuracy of spacecraft attitude estimation algorithms that use gyro data for propagating the spacecraft attitude is sensitive to gyro noise. EUVE gyro data were processed to validate a single-axis gyro noise model, which is used onboard various spacecraft. The paper addresses the potential impact of temperature effects on the gyro noise model and the overall impact on attitude determination accuracy. The power spectral density (PSD) of the gyro noise is estimated from UARS in-flight data by Fast Fourier Transform (FFT). The role of actuator dynamics on the PSD function is also discussed

Aquatic treadmill running reduces muscle soreness following intense sprint exercise in trained men

Delayed onset muscle soreness is associated with muscle damage, disturbances in proprioception, and decreases in muscular power. The purpose was to determine if short duration aquatic treadmill (ATM) running reduces muscle soreness following intense sprint exercise in trained men. Twenty trained men (180.3±4.4cm, 86.3±5.8kg, 20±1yr) were recruited and randomly divided into two groups: ATM recovery (ATMRec) and passive recovery (PRec). During testing, subjects performed a warm-up followed by sixteen 110yrd cutback runs with a sprint of 60yrds, sharp change of direction, and a return sprint of 50yrds. Work to rest ratio was set at 1:3. Additionally, following exercise, the ATMRec group performed ATM running using a HydroWorx® treadmill at 5mph, 50% maximal jet resistance, and water(33°C) level at chest depth for 10min. Both groups then evaluated their level of soreness/pain using a numerical rating scale (NRS: 0-10, 0=no pain, 10=worst pain) immediately following all exercise (IPE), 24h, and 48h post exercise in the following regions: ARMS, LEGS, BACK, CHEST, SHOULDERS, HIPS, ABDOMEN, NECK, OVERALL. Data were analyzed for group x time interactions using a 2x3 Generalized Linear Mixed Model for non-parametric data (α≤0.05). For significant interactions, the same procedure was used to analyze between group differences at the same measurement timepoint(α≤0.05)

Bis(N′-{(E)-[(2E)-1,3-diphenylprop-2-en-1-ylidene]amino}-N-ethylcarbamimidothioato-κ2 N′,S)zinc(II): crystal structure and Hirshfeld surface analysis

The title ZnII complex, [Zn(C18H18N3S)2], (I), features two independent but chemically equivalent molecules in the asymmetric unit. In each, the thiosemicarbazonate monoanion coordinates the ZnII atom via the thiolate-S and imine-N atoms, with the resulting N2S2 donor set defining a distorted tetrahedral geometry. The five-membered ZnSCN2 chelate rings adopt distinct conformations in each independent molecule, i.e. one ring is almost planar while the other is twisted about the Zn—S bond. In the crystal, the two molecules comprising the asymmetric unit are linked by amine-N—H...N(imine) and amine-N—H...S(thiolate) hydrogen bonds via an eight-membered heterosynthon, {...HNCN...HNCS}. The dimeric aggregates are further consolidated by benzene-C—H...S(thiolate) interactions and are linked into a zigzag supramolecular chain along the c axis via amine-N—H...S(thiolate) hydrogen bonds. The chains are connected into a three-dimensional architecture via phenyl-C—H...π(phenyl) and π–π interactions, the latter occurring between chelate and phenyl rings [inter-centroid separation = 3.6873 (11) Å]. The analysis of the Hirshfeld surfaces calculated for (I) emphasizes the different interactions formed by the independent molecules in the crystal and the impact of the π–π interactions between chelate and phenyl rings

Bis(4-methoxychalcone 4-ethylthiosemicarbazonato-κ2 N 1,S)zinc(II): Crystal structure and Hirshfeld surface analysis

The title ZnII complex, [Zn(C19H20N3OS)2] {systematic name: bis[(N-ethyl-N0-{(Z)-[(2E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-ylidene]amino}carbamimidoyl)sulfanido]zinc(II)}, features a tetrahedrally coordinated ZnII ion within an N2S2 donor set provided by two N,S-chelating thiosemicarbazone anions. The resulting five-membered Zn,C,N2,S chelate rings adopt different conformations, i.e. almost planar and an envelope with the Zn atom being the flap atom. The configuration about the imine bond within the chelate ring is Z but those about the exocyclic imine and ethylene bonds are E. In the crystal, supramolecular [100] chains mediated by thioamide-N—H...S(thione) hydrogen bonds and eight-membered thioamide {.....HNCS}2 synthons are observed. A range of interactions, including C—H...O, C—H...., C—H....(chelate ring) and .(methoxybenzene)—.(chelate ring) consolidate the packing. The Hirshfeld surface analysis performed on the title complex also indicates the influence of the interactions involving the chelate rings upon the packing along with the more conventional contacts

N′-[Bis(benzyl­sulfan­yl)methyl­idene]benzohydrazide

In the title hydrazonodithio­ate, C21H19N3OS2, the amide group is twisted out of the plane through the S2C=N atoms: the C—N—N—C torsion angle is 139.71 (13)°. The pyridine ring forms dihedral angles of 52.96 (8) and 86.46 (8)° with the phenyl rings, and the latter are approximately orthogonal [dihedral angle = 76.42 (9)°]. Supra­molecular chains sustained by N—H⋯O hydrogen bonds and propagated by glide symmetry along the c axis are found in the crystal structure. The chains are consolidated into a three-dimensional architecture by C—H⋯O and C—H⋯N inter­actions

(Pyridin-4-yl)methyl N′-(3-phenylallylidene)hydrazinecarbodithio­ate.

In the title compound, C16H15N3S2, the central C2N2S2 residue is planar (r.m.s. deviation = 0.045 Å) and the pyridyl and benzene rings are inclined and approximately coplanar to this plane, respectively [dihedral angles = 72.85 (9) and 10.73 (9)°], so that, overall, the mol­ecule adopts an L-shape. The conformation about each of the N=C [1.290 (3) Å] and C=C [1.340 (3) Å] bonds is E. Supra­molecular chains along [1-10] are stabilized by N—H(...)N(pyridine) hydrogen bonding and these are connected into a double layer that stacks along the c-axis direction by C—H(...)π(pyridine) inter­actions

METALLOGRAPHIC EXAMINATION OF ORNL NO. 1, SHE NO. 2

Small Heat Exchanger ORNL No. I, type SHE No. 2, was removed from test stand B after 2071 hours of operation; 1041 hours were under 4 T conditions. The heat exchanger contatned 20 Inconel tubes having an outside diameter of 0.25 in. and a wall thickness of 0.025 in. The outside of these tubes was exposed to the fluoride mixture NaF contained NaK (44% Na--56% K). During o degradation t T conditions, the fluoride temperature entering the heat exchanger was 1310 tained F and on leaving was 1235 tained F. The temperature of the NaK entering the heat exchanger was 1050 tained F and at the exit was 1290 tained F. During isothermal operation, the temperature of both the NaK and fluoride circuits was 1300 tained F. Thirtysix termperature transitions from isothermal to o degradation t T conditions were made during the course of operation. An examination of the resistance heater used in conjunction with this heat exchanger also was made: the results are reported. (auth

Synthesis, characterization and bioactivity of mixed-ligand Cu(II) complexes containing Schiff bases derived from S-benzyldithiocarbazate and saccharinate ligand and the X-ray crystal structure of the copper-saccharinate complex containing S-benzyl-β-N-(acetylpyrid-2-yl)methylenedithiocarbazate

Mixed-ligand complexes of general formula, [Cu(NNS)(sac)] (NNS′ = S-benzyl-β-N-(2-acetylpyrid-2-yl)methylenedithiocarbazate, NNS″ = S-benzyl-β-N-(2-benzoylpyrid-2-yl)methylenedithiocarbazate and NNS = S-benzyl-β-N-(6-methylpyrid-2-yl)methylenedithio-carbazate, sac = the saccharinate anion) have been synthesized by reacting [Cu(sac)2(H2O)4] · 2H2O with the appropriate ligands in ethanol and characterized by various physico-chemical techniques. Magnetic and spectral evidence indicate that the complexes are four-coordinate in which the Schiff bases coordinate as NNS ligands and the sac- anion coordinates as a unidentate N-donor ligand. An X-ray crystallographic structural analysis of [Cu(NNS′)(sac)] shows that the complex has a distorted square-planar geometry with the Schiff base coordinated to the copper (II) ion as a uninegatively charged tridentate chelating agent via the pyridine nitrogen atom, the azomethine nitrogen atom and the thiolate sulphur atom while the fourth coordination position is occupied by the N-bonded saccharinate anion. The complexes have been evaluated for their biological activities against selected pathogens and cancer cell lines. They display weak activity against the pathogenic bacteria and fungi. The complexes were highly active against the leukemic cell line (HL-60) but only [Cu(NNS′)(sac)] was found to exhibit strong cytotoxicity against the ovarian cancer cell line (Caov-3). All complexes were inactive against the breast cancer cell line (MCF-7)