The v-MFG test: Investigating maternal, offspring and maternal-fetal genetic incompatibility effects on disease and viability

The MFG test is a family-based association test that detects genetic effects contributing to disease in offspring, including offspring allelic effects, maternal allelic effects and MFG incompatibility effects. Like many other family-based association tests, it assumes that the offspring survival and the offspring-parent genotypes are conditionally independent provided the offspring is affected. However, when the putative disease-increasing locus can affect another competing phenotype, for example, offspring viability, the conditional independence assumption fails and these tests could lead to incorrect conclusions regarding the role of the gene in disease. We propose the v-MFG test to adjust for the genetic effects on one phenotype, e.g., viability, when testing the effects of that locus on another phenotype, e.g., disease. Using genotype data from nuclear families containing parents and at least one affected offspring, the v-MFG test models the distribution of family genotypes conditional on offspring phenotypes. It simultaneously estimates genetic effects on two phenotypes, viability and disease. Simulations show that the v-MFG test produces accurate genetic effect estimates on disease as well as on viability under several different scenarios. It generates accurate type-I error rates and provides adequate power with moderate sample sizes to detect genetic effects on disease risk when viability is reduced. We demonstrate the v-MFG test with HLA-DRB1 data from study participants with rheumatoid arthritis (RA) and their parents, we show that the v-MFG test successfully detects an MFG incompatibility effect on RA while simultaneously adjusting for a possible viability loss.

A new two point method of obtaining Cv from a consolidation test: Discussion

Careful study of various aspects presented in the note reveals basic fallacies in the concept and final conclusions.The Authors claim to have presented a new method of determining C-v. However, the note does not contain a new method. In fact, the method proposed is an attempt to generate settlement vs. time data using only two values of (t,8). The Authors have used a rectangular hyperbola method to determine C-v from the predicated 8- t data. In this context, the title of the paper itself is misleading and questionable. The Authors have compared C-v values predicated with measured values, both of them being the results of the rectangular hyperbola method.

T chart to evaluate consolidation test results

Using Terzaghi's degree of consolidation, U, and the time factor, T, relationship, if M-U1 and M-U2 (M-U1 not equal M-U2) are slopes of the U-root T curve at any two time factors T-U1 and T-U2, then it can be shown that a unique relationship exists between T-U2/T-U1, M-U1/M-U2, and TU, (or TU2), and knowing any two of these, the third can be uniquely determined. A chart, called the T chart, has been plotted using these three variables for quickly determining T and U at any experimental time, t, to determine the coefficient of consolidation, c(v), corrected zero settlement, delta(o), and ultimate primary settlement, delta(100). The chart can be used even in those cases where settlement and time, at the instant of load increment, are not known.

The effect of pH on the unfolding pathway and stability of ribosome-inactivating protein abrin-II

The effect of pH on the unfolding pathway acid the stability of the toxic protein abrin-II have been studied by increasing denaturant concentrations of guanidine hydrochloride and by monitoring the change in 8,1-anilino naphthalene sulfonic acid (ANS) fluorescence upon binding to the hydrophobic sites of the protein. Intrinsic protein fluorescence, far and near UV-circular dichroism (CD) spectroscopy and ANS binding studies reveal that the unfolding of abrin-II occurs through two intermediates at pH 7.2 and one intermediate at pH 4.5. At pH 7.2, the two subunits A and B of abrin-II unfold sequentially. The native protein is more stable at pH 4.5 than at pH 7.2. However, the stability of the abrin-II A-subunit is not affected by a change in pH. These observations may assist in an understanding of the physiologically relevant transmembrane translocation of the toxin.

Thermodynamic characterization of the conformational stability of the homodimeric protein, pea lectin

The conformational stability of the homodimeric pea lectin was determined by both isothermal urea-induced and thermal denaturation in the absence and presence of urea. The denaturation profiles were analyzed to obtain the thermodynamic parameters associated with the unfolding of the protein. The data not only conform to the simple A(2) double left right arrow 2U model of unfolding but also are well described by the linear extrapolation model for the nature of denaturant-protein interactions. In addition, both the conformational stability (Delta G(s)) and the Delta C-p for the protein unfolding is quite high, at about 18.79 kcal/ mol and 5.32 kcal/(mol K), respectively, which may be a reflection of the relatively larger size of the dimeric molecule (M-r 49 000) and, perhaps, a consequent larger buried hydrophobic core in the folded protein. The simple two-state (A(2) double left right arrow 2U) nature of the unfolding process, with the absence of any monomeric intermediate, suggests that the quaternary interactions alone may contribute significantly to the conformational stability of the oligomer-a point that may be general to many oligomeric proteins.

Improved root t method to evaluate consolidation test results - Discussion

Taylor (1948) suggested the method for determination of the settlement, d, corresponding to 90% consolidation utilizing the characteristics of the degree of consolidation, U, versus the square root of the time factor, square root of T, plot. Based on the properties of the slope of U versus square root of T curve, a new method is proposed to determine d corresponding to any U above 70% consolidation for evaluation of the coefficient of consolidation, Cn. The effects of the secondary consolidation on the Cn value at different percentages of consolidation can be studied. Cn, closer to the field values, can be determined in less time as compared to Taylor's method. At any U in between 75 and 95% consolidation, Cn(U) due to the new method lies in between Taylor's Cn and Casagrande's Cn.

Glass forming ability and stability: Ternary Cu bearing Ti, Zr, Hf alloys

Four Cu bearing alloys of nominal composition Zr25Ti25Cu50, Zr34Ti16Cu50, Zr25Hf25Cu50 and Ti25Hf25Cu50 have been rapidly solidified in order to produce ribbons. All the alloys become amorphous after meltspinning. In the Zr34Ti16Cu50 alloy localized precipitation of cF24 Cu5Zr phase can be observed in the amorphous matrix. The alloys show a tendency of phase separation at the initial stages of crystallization. The difference in crystallization behavior of these alloys with Ni bearing ternary alloys can be explained by atomic size, binary heat of mixing and Mendeleev number. It has been observed that both Laves and Anti-Laves phase forming compositions are suitable for glass formation. The structures of the phases, precipitated during rapid solidification and crystallization can be viewed in terms of Bernal deltahedra and Frank-Kasper polyhedra.

Stability of a Random Diffusion with Linear Drift

We consider a Linear system with Markovian switching which is perturbed by Gaussian type noise, If the linear system is mean square stable then we show that under certain conditions the perturbed system is also stable, We also shaw that under certain conditions the linear system with Markovian switching can be stabilized by such noisy perturbation.

Hingeless-rotor aeromechanical stability in axial and forward flight with wake dynamics

A finite-state wake model is used to investigate aeromechanical stability of hingeless-rotor helicopters in the ground-contact, hover and trimmed-night conditions. The investigation covers three items: (1) the convergence of the damping with increasing number of wake harmonics for the lag regressing, and body pitch and roll modes; (2) a parametric study of the damping over a range of thrust level, advance ratio and number of blades; and (3) correlations, primarily with the damping and frequency measurements of these lag and body modes. The convergence and parametric studies are conducted in the hover and trimmed-flight conditions; they include predictions from the widely used dynamic inflow model. The correlations are conducted in the ground-contact conditions and include predictions from the dynamic inflow and vortex models; recently, this vortex model is proposed for the axial-flight conditions and is used to investigate the coupled free vibrations of rotor flapping and body modes. The convergence and parametric studies show that a finite-state wake model that goes well beyond the dynamic inflow model is required for fairly converged damping, Moreover, the correlations from the finite-state wake, dynamic inflow and vortex models are generally satisfactory.

A new intelligent algorithm for online voltage stability assessment and monitoring

This paper presents a new approach for assessing power system voltage stability based on artificial feed forward neural network (FFNN). The approach uses real and reactive power, as well as voltage vectors for generators and load buses to train the neural net (NN). The input properties of the NN are generated from offline training data with various simulated loading conditions using a conventional voltage stability algorithm based on the L-index. The performance of the trained NN is investigated on two systems under various voltage stability assessment conditions. Main advantage is that the proposed approach is fast, robust, accurate and can be used online for predicting the L-indices of all the power system buses simultaneously. The method can also be effectively used to determining local and global stability margin for further improvement measures.

Stability of Dimeric Interface in Banana Lectin: Insight from Molecular Dynamics Simulations

Banana lectin (Banlec) is a homodimeric non-glycosylated protein. It exhibits the b-prism I structure. High-temperature molecular dynamics simulations have been utilized to monitor and understand early stages of thermally induced unfolding of Banlec. The present study elucidates the behavior of the dimeric protein at four different temperatures and compares the structural and conformational changes to that of the minimized crystal structure. The process of unfolding was monitored by following the radius of gyration, the rms deviation of each residue, change in relative solvent accessibility and the pattern of inter- and intra-subunit interactions. The overall study demonstrates that the Banlec dimer is a highly stable structure, and the stability is mostly contributed by interfacial interactions. It maintains its overall conformation during high-temperature (400–500 K) simulations, with only the unstructured loop regions acquiring greater momentum under such condition. Nevertheless, at still higher temperatures (600 K) the tertiary structure is gradually lost which later extends to loss of secondary structural elements. The pattern of hydrogen bonding within the subunit and at the interface across different stages has been analyzed and has provided rationale for its intrinsic high stability.

Response And Stability Of A Stochastic Beam-Column Using Stochastic Fem

A beam-column resting on continuous Winkler foundation and discrete elastic supports is considered. The beam-column is of variable cross-section and the variation of sectional properties along the axis of the beam-column is deterministic. Young's modulus, mass per unit length and distributed axial loadings of the beam-column have a stochastic distribution. The foundation stiffness coefficient of the Winkler model, the stiffnesses of discrete elastic supports, stiffnesses of end springs and the end thrust, are all considered as random parameters. The material property fluctuations and distributed axial loadings are considered to constitute independent, one-dimension uni-variate homogeneous real stochastic fields in space. The foundation stiffness coefficient, stiffnesses of the discrete elastic supports, stiffnesses of end springs and the end thrust are considered to constitute independent random variables. Static response, free vibration and stability behaviour of the beam-column are studied. Hamilton's principle is used to formulate the problem using stochastic FEM. Sensitivity vectors of the response and stability parameters are evaluated. Using these statistics of free vibration frequencies, mode shapes, buckling parameters, etc., are evaluated. A numerical example is given.

Stability of pargasite during ultrahigh-temperature metamorphism:A consequence of titanium and REE partitioning

Orthopyroxene-clinopyroxene-plagioclase needles and symplectite along the cleavage planes and grain boundaries of fluorine-bearing titanian-ferroan pargasite from the Highland Complex, Sri Lanka, are interpreted as evidence for dehydration melting at ultrahigh-temperature conditions. High Ti (up to 0.4 pfu) and F (XF up to 0.56) content in pargasite extends its stability to higher temperatures, and the composition indicates the dehydration melting reaction may take place at ultrahigh-temperatures (~950 °C) at a pressure around 10 kbar, close to peak metamorphic conditions. The increase of Ti content close to the grain boundaries and cleavage planes in pargasite indicates titanium partitioning from the melt during dehydration melting enhanced the stability of the mineral toward ultrahigh-temperature conditions. The REE content in the pargasite shows a similar behavior to that of titanium. The cores with no breakdown assemblage consist of low and flat REE concentrations with respect to the high and Eu-depleted rim. Clinopyroxene in symplectite and needle-shaped lamellae within the pargasite porphyroblasts have similar REE patterns with slightly low-concentrations relative to that of pargasite. In the breakdown assemblage, LREEs are partitioned mainly into plagioclase while the HREEs are partitioned into orthopyroxene. The REE enrichment in the pargasite rims signals their relative partitioning between pargasite rims and melt. Modeling of the partitioning of Ti and REEs associated with pargasite breakdown demonstrates that its stability is greatly enhanced at UHT conditions. This investigation implies that the stability of hydrous minerals such as amphibole can be extended to UHT conditions, and expands our knowledge of metamorphism in the lower crust.

Nonlinear mechanical property of tracheal cartilage: A theoretical and experimental study

Background: Despite being the stiffest airway of the bronchial tree, the trachea undergoes significant deformation due to intrathoracic pressure during breathing. The mechanical properties of the trachea affect the flow in the airway and may contribute to the biological function of the lung. Method: A Fung-type strain energy density function was used to investigate the nonlinear mechanical behavior of tracheal cartilage. A bending test on pig tracheal cartilage was performed and a mathematical model for analyzing the deformation of tracheal cartilage was developed. The constants included in the strain energy density function were determined by fitting the experimental data. Result: The experimental data show that tracheal cartilage is a nonlinear material displaying higher strength in compression than in tension. When the compression forces varied from -0.02 to -0.03 N and from -0.03 to -0.04 N, the deformation ratios were 11.03±2.18% and 7.27±1.59%, respectively. Both were much smaller than the deformation ratios (20.01±4.49%) under tension forces of 0.02 to 0.01 N. The Fung-type strain energy density function can capture this nonlinear behavior very well, whilst the linear stress-strain relation cannot. It underestimates the stability of trachea by exaggerating the displacement in compression. This study may improve our understanding of the nonlinear behavior of tracheal cartilage and it may be useful for the future study on tracheal collapse behavior under physiological and pathological conditions.

The impact of wall shear stress and pressure drop on the stability of the atherosclerotic plaque

Rupture of vulnerable atheromatous plaque in the carotid and coronary arteries often leads to stroke and heart attack respectively. The mechanism of blood flow and plaque rupture in stenotic arteries is still not fully understood. A three dimensional rigid wall model was solved under steady state conditions and unsteady conditions by assuming a time-varying inlet velocity profile to investigate the relative importance of axial forces and pressure drops in arteries with asymmetric stenosis. Flow-structure interactions were investigated for the same geometry and the results were compared with those retrieved with the corresponding 2D cross-section structural models. The Navier-Stokes equations were used as the governing equations for the fluid. The tube wall was assumed hyperelastic, homogeneous, isotropic and incompressible. The analysis showed that the three dimensional behavior of velocity, pressure and wall shear stress is in general very different from that predicted by cross-section models. Pressure drop across the stenosis was found to be much higher than shear stress. Therefore, pressure may be the more important mechanical trigger for plaque rupture other than shear stress, although shear stress is closely related to plaque formation and progression.