Activation of the mouse heart adenosine 5',5"'-P1-P4-tetraphosphate receptor

We have previously demonstrated that mouse brain membrane fractions have a specific, saturable receptor for diadenylated nucleotides. Binding is specific for two adenosines, and the length of the phosphate bridge is critical, with four phosphates being optimal [Hilderman et al. (1991) J. Biol. Chem. 266, 6915-6918]. In this report, we demonstrate that adenosine 5',5"'-P1,P4-tetraphosphate (Ap4A) binding to its receptor is dependent upon an activation step that requires divalent cations and a serine protease. Monoclonal antibodies (Mabs) are identified that inhibit Ap4A binding to its membrane receptor. These antibodies recognize a 212-kDa membrane protein. However, SDS-PAGE analysis of Ap4A cross-linked to membrane fractions reveals that Ap4A is not attached to the 212-kDa peptide but to a 30-kDa polypeptide. Appearance of the 30-kDa polypeptide is dependent on the activation step, and one of the inhibitory antibodies blocks its appearance. We suggest that the protease-dependent processing step involves cleavage of the 212-kDa component with the appearance of an active 30-kDa receptor.     

Measurement of thrombus formation on intravascular catheters

War is a complex social situation due to the interplay of multiple factors. Economical and political ones are of utmost importance, but human attitudes and motivations must be also taken into account. Being desirable to modify human transactions in such a way that they do not interfere with the basic right of everyone to a condition of physical and mental well-being, war must be abolished. The author contends that an understanding of behaviour through Psychology can be helpful in that aim. Aggression is considered the principal psychological cause of war. It is worth while to differentiate between aggression as an instrument for attaining a special end, and as pure hostility. Only in the first form, it is held here, does it play an important role in war. Psychogists must deal also with a wide range of states of mind that can be "served" by aggression: feelings of inferiority or insecurity, fear, greed, projections, compensations, rationalizations, etc. Scientific approach is not the only one Physiology brings to war prevention. It is equally important the wide dissemination of its conclusions among the general public. Information on the dynamics that prompt people to decide war would make it easier to control. This applies not only to political or military leaders, but also to civil populations. Concerning those two possible contributions of psychologists, scientific and educative, it is suggested the extensive use of psychodramatic techniques. Their richness lie in the lifelike experiences they convey to the participants, and particular aptitude to promote changes of attitudes. Investigation and information on the psychological processes related to war should be undertaken by international organizations of social scientists, acting simultaneously in several countries. Some of the initial steps they could further: 1) that prevention of war be a current subject matter in psychological courses; 2) that the World Health Organization take interest in this subject; 3) that psychologists participate in international political and economical bodies in order to clarify the psychological factors leading to war.     

Nomemclature of the proteins of cow's milk: fourth revision.

This report reviews the nomenclature of the milk proteins of cow's milk in light of more recent advances in our knowledge. With the establishment of the primary structures of a number of these proteins, we now have a definite identification of alphas1-, kappa-, beta-, and the gamma-caseins as well as beta-lactoglobulin and alpha-lactalbumin. On the basis of new information on their primary structures and relationship to beta-casein polymorphs, changes in nomenclature have been recommended for proteins of the gamma-casein fraction. Although the primary structure serves as the unambiguous definition of proteins for which it is known, a more practical identification is necessary. We recommend that their behavior in gel electrophoresis under suitable conditions be employed for this purpose for all of the "major" milk proteins of raw skim milk except the immunoglobulins where, because of their heterogeneity and molecular genetics, physical parameters are less useful and their identification must be based upon antigenic determinants and their homology with their human counterparts. More work is needed and, with the accumulation of more information, additional changes in nomenclature can be expected for such proteins as the minor components of alphas- and kappa-caseins, alpha-lactalbumin, and the proteose-peptone fraction as well as further confirmation of the presence of immunoglobulins IgE and additional IgG subclasses. Additional components and genetic variants also can be expected.     

Calibration and validation of coarse-grained models of atomic systems: application to semiconductor manufacturing

Coarse-grained models of atomic systems, created by aggregating groups of atoms into molecules to reduce the number of degrees of freedom, have been used for decades in important scientific and technological applications. In recent years, interest in developing a more rigorous theory for coarse graining and in assessing the predictivity of coarse-grained models has arisen. In this work, Bayesian methods for the calibration and validation of coarse-grained models of atomistic systems in thermodynamic equilibrium are developed. For specificity, only configurational models of systems in canonical ensembles are considered. Among major challenges in validating coarse-grained models are (1) the development of validation processes that lead to information essential in establishing confidence in the model’s ability predict key quantities of interest and (2), above all, the determination of the coarse-grained model itself; that is, the characterization of the molecular architecture, the choice of interaction potentials and thus parameters, which best fit available data. The all-atom model is treated as the “ground truth,” and it provides the basis with respect to which properties of the coarse-grained model are compared. This base all-atom model is characterized by an appropriate statistical mechanics framework in this work by canonical ensembles involving only configurational energies. The all-atom model thus supplies data for Bayesian calibration and validation methods for the molecular model. To address the first challenge, we develop priors based on the maximum entropy principle and likelihood functions based on Gaussian approximations of the uncertainties in the parameter-to-observation error. To address challenge (2), we introduce the notion of model plausibilities as a means for model selection. This methodology provides a powerful approach toward constructing coarse-grained models which are most plausible for given all-atom data. We demonstrate the theory and methods through applications to representative atomic structures and we discuss extensions to the validation process for molecular models of polymer structures encountered in certain semiconductor nanomanufacturing processes. The powerful method of model plausibility as a means for selecting interaction potentials for coarse-grained models is discussed in connection with a coarse-grained hexane molecule. Discussions of how all-atom information is used to construct priors are contained in an appendix.     

Outlier accommodation in moving-horizon state estimation: A risk-averse performance-specified approach

This paper presents a novel state estimation approach for linear dynamic systems when measurements are corrupted by outliers. Since outliers can degrade the performance of state estimation, outlier accommodation is critical. The standard approach combines outlier detection utilizing Neyman-Pearson (NP) type tests with a Kalman filter (KF). This approach ignores all residuals greater than a designer-specified threshold. When measurements with outliers are used (ie, missed detections), both the state estimate and the error covariance matrix become corrupted. This corrupted state and covariance estimate are then the basis for all subsequent outlier decisions. When valid measurements are rejected (ie, false alarms), potentially using the corrupted state estimate and error covariance, measurement information is lost. Either using invalid information or discarding too much valid information can result in divergence of the KF. An alternative approach is moving-horizon (MH) state estimation, which maintains all recent measurement data within a moving window with a time horizon of length L. In MH approaches, the number of measurements available for state estimation is affected by both the number of measurements per time step and the number of time steps L over which measurements are retained. Risk-averse performance-specified (RAPS) state estimation works within an optimization setting to choose a set of measurements that achieves a performance specification with minimum risk of outlier inclusion. This paper derives and formulates the MH-RAPS solution for outlier accommodation. The paper also presents implementation results. The MH-RAPS application uses Global Navigation Satellite Systems measurements to estimate the state of a moving platform using a position, velocity, and acceleration model. In this application, MH-RAPS performance is compared with MH-NP state estimation.     

Comparing GC–MS,HPLC and H NMR analysis of beef longissimus dorsi tissue extracts to determine the effect of suspension technique and ageing

Beef longissimus dorsi muscle samples matured over a 21 day period were analysed using three different analytical techniques; ¹H NMR, GC–MS and HPLC. The data from the three experimental techniques were correlated with each other to determine if the results were statistically similar to each other. From our analysis we determined that the metabolites measured using ¹H NMR were statistically similar to the compounds quantified using the chromatography techniques (p < 0.001). In addition, using PCA, we were able to show that different metabolites, measured using the various analytical techniques produced very similar scores and loadings plots for all the analysis and extraction techniques undertaken across the 21 day time domain. Using a combination of these three different techniques provides a unique and holistic insight into the biochemistry behind the conversion of muscle to meat which would not be possible using any single technique alone.     

Consolidated theory of fluid thermodiffusion

We present the Onsager–Stefan–Maxwell thermodiffusion equations, which account for the Soret and Dufour effects in multicomponent fluids. Unlike transport laws derived from kinetic theory, this framework preserves the structure of the isothermal Stefan–Maxwell equations, separating the thermodynamic forces that drive diffusion from the force that drives heat flow. The Onsager–Stefan–Maxwell transport-coefficient matrix is symmetric, and the second law of thermodynamics imbues it with simple spectral characteristics. This new approach allows for heat to be considered as a pseudo-species and proves equivalent to both the intuitive extension of Fick's law and the generalized Stefan–Maxwell equations popularized by Bird, Stewart, and Lightfoot. A general inversion process facilitates the unique formulation of flux-explicit transport equations relative to any choice of convective reference velocity. Stefan–Maxwell diffusivities and thermal diffusion factors are tabulated for gaseous mixtures containing helium, argon, neon, krypton, and xenon. The framework is deployed to perform numerical simulations of steady three-dimensional thermodiffusion in a ternary gas.     

Site-Directed Immobilization of an Engineered Bone Morphogenetic Protein 2 (BMP2) Variant to Collagen-Based Microspheres Induces Bone Formation In Vivo

For the treatment of large bone defects, the commonly used technique of autologous bone grafting presents several drawbacks and limitations. With the discovery of the bone-inducing capabilities of bone morphogenetic protein 2 (BMP2), several delivery techniques were developed and translated to clinical applications. Implantation of scaffolds containing adsorbed BMP2 showed promising results. However, off-label use of this protein-scaffold combination caused severe complications due to an uncontrolled release of the growth factor, which has to be applied in supraphysiological doses in order to induce bone formation. Here, we propose an alternative strategy that focuses on the covalent immobilization of an engineered BMP2 variant to biocompatible scaffolds. The new BMP2 variant harbors an artificial amino acid with a specific functional group, allowing a site-directed covalent scaffold functionalization. The introduced artificial amino acid does not alter BMP2′s bioactivity in vitro. When applied in vivo, the covalently coupled BMP2 variant induces the formation of bone tissue characterized by a structurally different morphology compared to that induced by the same scaffold containing ab-/adsorbed wild-type BMP2. Our results clearly show that this innovative technique comprises translational potential for the development of novel osteoinductive materials, improving safety for patients and reducing costs.     

Influence of bovine and caprine casein phosphopeptides differing in alphas1-casein content in determining the absorption of calcium from bovine and caprine calcium-fortified milks in rats

Bovine and caprine milks have a similar overall gross composition, but vary considerably in the ratios of their casein components. These differences cause significant changes in the ability of caseins to bind and stabilize calcium (Ca). It might be expected that these in vitro variations, which are thought to be due to differences in casein phosphopeptides (CPP) content, could lead to in vivo differences in the digestion and absorption of Ca. To test this hypothesis three milks with different casein ratios [bovine (B), caprine high in alphas1-casein (CH) and caprine low in alphas1-casein (CL)] were compared with regard to Ca absorption and deposition in growing male rats. For comparison, each milk was Ca-fortified (BCa-milk, CHCa-milk, and CLCa-milk) and CPP, prepared by enzymatic hydrolysis from the respective caseins (extrinsic CPP), were added to both native and Ca-milks. The effects of added CPP (extrinsic) could then be compared with intrinsic CPP released from the gastrointestinal digestion of caseins. Total gastric Ca was sampled at 15, 30 and 60 min after ingestion. No differences were found among the native milks with or without CPP, but the Ca from all Ca-milks (regardless of casein type) appeared to clear the stomach more rapidly and this was enhanced by the extrinsic CPP. The total intestinal Ca was not different among the native milks+/-CPP, however, it rose more rapidly with Ca fortification, and was higher at 30 min for all CPP-Ca-milks. At 60 min the total intestinal Ca level fell for the CPP-Ca-milks while all others continued to rise. These observations suggest that the CPP in Ca-milks enhance gastric clearance and uptake from the intestine. Ca availability from BCa-milk, CHCa-milk, and CLCa-milk with and without CPP was estimated by both plasma and femur uptake of 45Ca. Ca availability was enhanced at 5 h in the plasma in each case by added CPP. In all cases CPP stimulated Ca availability in the femur, but the CL-CPP was higher (P<0.05) than that of either CH-CPP or B-CPP (extrinsic CPP). Based on the results of this study we can conclude that the addition of CPP will have beneficial effect on the absorption of Ca in growing rats from CaCO3 added to bovine and caprine milks.     

Relative fat oxidation is higher in children than adults

Background  

Prepubescent children may oxidize fatty acids more readily than adults. Therefore, dietary fat needs would be higher for children compared with adults. The dietary fat recommendations are higher for children 4 to 18 yrs (i.e., 25 to 35% of energy) compared with adults (i.e., 20 to 35% of energy). Despite this, many parents and children restrict dietary fat for health reasons.