Polyphosphate in thrombosis, hemostasis, and inflammation

This illustrated review focuses on polyphosphate as a potent modulator of the plasma clotting cascade, with possible roles in hemostasis, thrombosis, and inflammation. Polyphosphates are highly anionic, linear polymers of inorganic phosphates that are widespread throughout biology. Infectious microorganisms accumulate polyphosphates with widely varying polymer lengths (from a few phosphates to over a thousand phosphates long), while activated human platelets secrete polyphosphate with a very narrow size distribution (about 60‐100 phosphates long). Work from our lab and others has shown that long‐chain polyphosphate is a potent trigger of clotting via the contact pathway, while polyphosphate of the size secreted by platelets accelerates factor V activation, blocks the anticoagulant activity of tissue factor pathway inhibitor, promotes factor XI activation by thrombin, and makes fibrin fibrils thicker and more resistant to fibrinolysis. Polyphosphate also modulates inflammation by triggering bradykinin release, inhibiting the complement system, and modulating endothelial function. Polyphosphate and nucleic acids have similar physical properties and both will trigger the contact pathway—although polyphosphate is orders of magnitude more procoagulant than either DNA or RNA. Important caveats in these studies include observations that nucleic acids and polyphosphate may co‐purify, and that these preparations can be contaminated with highly procoagulant microparticles if silica‐based purification methods are employed. Polyphosphate has received attention as a possible therapeutic, with some recent studies exploring the use of polyphosphate in a variety of formulations to control bleeding. Other studies are investigating treatments that block polyphosphate function as novel antithrombotics with the possibility of reduced bleeding side effects.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147856/1/rth212162_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147856/2/rth212162.pd

Holomorphic selection rules, the origin of the mu term, and thermal inflation

When an abelian gauge theory with integer charges is spontaneously broken by the expectation value of a charge Q field, there remains a Z_Q discrete symmetry. In a supersymmetric theory, holomorphy adds additional constraints on the operators that can appear in the effective superpotential. As a result, operators with the same mass dimension but opposite sign charges can have very different coupling strengths. In the present work we characterize the operator hierarchies in the effective theory due to holomorphy, and show that there exist simple relationships between the size of an operator and its mass dimension and charge. Using such holomorphy-induced operator hierarchies, we construct a simple model with a naturally small supersymmetric mu term. This model also provides a concrete realization of late-time thermal inflation, which has the ability to solve the gravitino and moduli problems of weak-scale supersymmetry.Comment: 18 pages, 1 figur

Ultrasound Measurement of Local Deformation in the Human Free Achilles Tendon Produced by Dynamic Muscle-Induced Loading: A Systematic Review.

Achilles tendinopathy is the most prevalent lower limb tendinopathy, yet it remains poorly understood, with mismatches between observed structure and reported function. Recent studies have hypothesised that Achilles tendon (AT) healthy function is associated with variable deformation across the tendon width during use, focusing on quantifying sub-tendon deformation. Here, the aim of this work was to synthesise recent advances exploring human free AT tissue-level deformation during use. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, PubMed, Embase, Scopus and Web of Science were systematically searched. Study quality and risk of bias were assessed. Thirteen articles were retained, yielding data on free AT deformation patterns. Seven were categorised as high-quality and six as medium-quality studies. Evidence consistently reports that healthy and young tendons deform non-uniformly, with the deeper layer displacing 18%-80% more than the superficial layer. Non-uniformity decreased by 12%-85% with increasing age and by 42%-91% in the presence of injury. There is limited evidence of large effect that AT deformation patterns during dynamic loading are non-uniform and may act as a biomarker of tendon health, risk of injury and rehabilitation impact. Better considered participant recruitment and improved measurement procedures would particularly improve study quality, to explore links between tendon structure, function, aging and disease in distinct populations

Enhanced Production of Neutron-Rich Rare Isotopes in Peripheral Collisions at Fermi Energies

A large enhancement in the production of neutron-rich projectile residues is observed in the reactions of a 25 MeV/nucleon 86Kr beam with the neutron rich 124Sn and 64Ni targets relative to the predictions of the EPAX parametrization of high-energy fragmentation, as well as relative to the reaction with the less neutron-rich 112Sn target. The data demonstrate the significant effect of the target neutron-to-proton ratio (N/Z) in peripheral collisions at Fermi energies. A hybrid model based on a deep-inelastic transfer code (DIT) followed by a statistical de-excitation code appears to account for part of the observed large cross sections. The DIT simulation indicates that the production of the neutron-rich nuclides in these reactions is associated with peripheral nucleon exchange. In such peripheral encounters, the neutron skins of the neutron-rich 124Sn and 64Ni target nuclei may play an important role. From a practical viewpoint, such reactions between massive neutron-rich nuclei offer a novel and attractive synthetic avenue to access extremely neutron-rich rare isotopes towards the neutron-drip line.Comment: 4 pages, 3 figures, submitted to Phys. Rev. Let

Crack Front Waves and the dynamics of a rapidly moving crack

Crack front waves are localized waves that propagate along the leading edge of a crack. They are generated by the interaction of a crack with a localized material inhomogeneity. We show that front waves are nonlinear entities that transport energy, generate surface structure and lead to localized velocity fluctuations. Their existence locally imparts inertia, which is not incorporated in current theories of fracture, to initially "massless" cracks. This, coupled to crack instabilities, yields both inhomogeneity and scaling behavior within fracture surface structure.Comment: Embedded Latex file including 4 figure

Nuclear rockets based on graphite reactor technology - Their applications and development status

Development and mission applications of nuclear rockets based on graphite reactor technolog

Dynamics and Instabilities of Planar Tensile Cracks in Heterogeneous Media

The dynamics of tensile crack fronts restricted to advance in a plane are studied. In an ideal linear elastic medium, a propagating mode along the crack front with a velocity slightly less than the Rayleigh wave velocity, is found to exist. But the dependence of the effective fracture toughness $\Gamma(v)$ on the crack velocity is shown to destabilize the crack front if $(d\Gamma)/(dv)<0$. Short wavelength radiation due to weak random heterogeneities leads to this instability at low velocities. The implications of these results for the crack dynamics are discussed.Comment: 12 page

Structural, item, and test generalizability of the psychopathology checklist - revised to offenders with intellectual disabilities

The Psychopathy Checklist–Revised (PCL-R) is the most widely used measure of psychopathy in forensic clinical practice, but the generalizability of the measure to offenders with intellectual disabilities (ID) has not been clearly established. This study examined the structural equivalence and scalar equivalence of the PCL-R in a sample of 185 male offenders with ID in forensic mental health settings, as compared with a sample of 1,212 male prisoners without ID. Three models of the PCL-R’s factor structure were evaluated with confirmatory factor analysis. The 3-factor hierarchical model of psychopathy was found to be a good fit to the ID PCL-R data, whereas neither the 4-factor model nor the traditional 2-factor model fitted. There were no cross-group differences in the factor structure, providing evidence of structural equivalence. However, item response theory analyses indicated metric differences in the ratings of psychopathy symptoms between the ID group and the comparison prisoner group. This finding has potential implications for the interpretation of PCL-R scores obtained with people with ID in forensic psychiatric settings

Design Equation: A Novel Approach to Heteropolymer Design

A novel approach to heteropolymer design is proposed. It is based on the criterion by Kurosky and Deutsch, with which the probability of a target conformation in a conformation space is maximized at low but finite temperature. The key feature of the proposed approach is the use of soft spins (fuzzy monomers) that leads to a design equation, which is an analog of the Boltzmann machine learning equation in the design problem. We implement an algorithm based on the design equation for the generalized HP model on the 3x3x3 cubic lattice and check its performance.Comment: 7 pages, 3 tables, 1 figures, uses jpsj.sty, jpsjbs1.sty, epsf.sty, Submitted to J. Phys. Soc. Jp