Animal Models of Thrombosis From Zebrafish to Nonhuman Primates: Use in the Elucidation of New Pathologic Pathways and the Development of Antithrombotic Drugs

Thrombosis is a leading cause of morbidity and mortality worldwide. Animal models are used to understand the pathological pathways involved in thrombosis and to test the efficacy and safety of new antithrombotic drugs. In this review, we will first describe the central role a variety of animal models of thrombosis and hemostasis has played in the development of new antiplatelet and anticoagulant drugs. These include the widely used P2Y12 antagonists and the recently developed orally available anticoagulants that directly target factor Xa or thrombin. Next, we will describe the new players, such as polyphosphate, neutrophil extracellular traps, and microparticles, which have been shown to contribute to thrombosis in mouse models, particularly venous thrombosis models. Other mouse studies have demonstrated roles for the factor XIIa and factor XIa in thrombosis. This has spurred the development of strategies to reduce their levels or activities as a new approach for preventing thrombosis. Finally, we will discuss the emergence of zebrafish as a model to study thrombosis and its potential use in the discovery of novel factors involved in thrombosis and hemostasis. Animal models of thrombosis from zebrafish to nonhuman primates are vital in identifying pathological pathways of thrombosis that can be safely targeted with a minimal effect on hemostasis. Future studies should focus on understanding the different triggers of thrombosis and the best drugs to prevent each type of thrombotic event

Dilute Multi Alpha Cluster States in Nuclei

Dilute multi $\alpha$ cluster condensed states with spherical and axially deformed shapes are studied with the Gross-Pitaevskii equation and Hill-Wheeler equation, where the $\alpha$ cluster is treated as a structureless boson. Applications to self-conjugate $4N$ nuclei show that the dilute $N\alpha$ states of $^{12}$C to $^{40}$Ca with $J^\pi=0^+$ appear in the energy region from threshold up to about 20 MeV, and the critical number of $\alpha$ bosons that the dilute $N\alpha$ system can sustain as a self-bound nucleus is estimated roughly to be $N_{cr}\sim10$. We discuss the characteristics of the dilute $N\alpha$ states with emphasis on the $N$ dependence of their energies and rms radii.Comment: 44 pages, 8 figure

Schrodinger equation for the one particle density matrix of thermal systems: An alternative formulation of Bose-Einstein condensation

We formulate a linear Schrodinger equation with the temperature-dependent potential for the one-particle density matrix and obtain the condensation temperature of the Bose-Einstein condensate from a bound-state condition for the Schrodinger equation both with and without the confining trap. The results are in very good agreement with those of the full statistical physics treatment. This is an alternative to the Bose-Einstein condensation in the standard ideal Bose gas treatment.Comment: 4 pages, 2 figure

The Origins of Phase Transitions in Small Systems

The identification and classification of phases in small systems, e.g. nuclei, social and financial networks, clusters, and biological systems, where the traditional definitions of phase transitions are not applicable, is important to obtain a deeper understanding of the phenomena observed in such systems. Within a simple statistical model we investigate the validity and applicability of different classification schemes for phase transtions in small systems. We show that the whole complex temperature plane contains necessary information in order to give a distinct classification.Comment: 3 pages, 4 figures, revtex 4 beta 5, for further information see http://www.smallsystems.d

The longitudinal development of emotion regulation capacities in children at risk for externalizing disorders

The development of emotional regulation capacities in children at high versus low risk for externalizing disorder was examined in a longitudinal study investigating: a) whether disturbances in emotion regulation precede and predict the emergence of externalizing symptoms; and b) whether sensitive maternal behavior is a significant influence on the development of child emotion regulation. Families experiencing high (n=58) and low (n=63) levels of psychosocial adversity were recruited to the study during pregnancy. Direct observational assessments of child emotion regulation capacities and maternal sensitivity were completed in early infancy, at 12 and 18-months, and at 5-years. Key findings were as follows. First, high risk children showed poorer emotion regulation capacities than their low risk counterparts at every stage of assessment. Second, from 12-months onwards, emotion regulation capacities showed a degree of stability, and were associated with behavioral problems, both concurrently and prospectively. Third, maternal sensitivity was related to child emotion regulation capacities throughout development, with poorer emotion regulation in the high risk group being associated with lower maternal sensitivity. The results are consistent with a causal role for problems in the regulation of negative emotions in the etiology of externalizing psychopathology, and highlight insensitive parenting as a potentially key developmental influence

Complete High Temperature Expansions for One-Loop Finite Temperature Effects

We develop exact, simple closed form expressions for partition functions associated with relativistic bosons and fermions in odd spatial dimensions. These expressions, valid at high temperature, include the effects of a non-trivial Polyakov loop and generalize well-known high temperature expansions. The key technical point is the proof of a set of Bessel function identities which resum low temperature expansions into high temperature expansions. The complete expressions for these partition functions can be used to obtain one-loop finite temperature contributions to effective potentials, and thus free energies and pressures.Comment: 9 pages, RevTeX, no figures. To be published in Phys. Rev D. v2 has revised introduction and conclusions, plus a few typographical errors are corrected; v3 corrects one typ

Haloquadratum walsbyi : Limited Diversity in a Global Pond

BACKGROUND: Haloquadratum walsbyi commonly dominates the microbial flora of hypersaline waters. Its cells are extremely fragile squares requiring >14%(w/v) salt for growth, properties that should limit its dispersal and promote geographical isolation and divergence. To assess this, the genome sequences of two isolates recovered from sites at near maximum distance on Earth, were compared. PRINCIPAL FINDINGS: Both chromosomes are 3.1 MB in size, and 84% of each sequence was highly similar to the other (98.6% identity), comprising the core sequence. ORFs of this shared sequence were completely synteneic (conserved in genomic orientation and order), without inversion or rearrangement. Strain-specific insertions/deletions could be precisely mapped, often allowing the genetic events to be inferred. Many inferred deletions were associated with short direct repeats (4-20 bp). Deletion-coupled insertions are frequent, producing different sequences at identical positions. In cases where the inserted and deleted sequences are homologous, this leads to variant genes in a common synteneic background (as already described by others). Cas/CRISPR systems are present in C23(T) but have been lost in HBSQ001 except for a few spacer remnants. Numerous types of mobile genetic elements occur in both strains, most of which appear to be active, and with some specifically targetting others. Strain C23(T) carries two ∼6 kb plasmids that show similarity to halovirus His1 and to sequences nearby halovirus/plasmid gene clusters commonly found in haloarchaea. CONCLUSIONS: Deletion-coupled insertions show that Hqr. walsbyi evolves by uptake and precise integration of foreign DNA, probably originating from close relatives. Change is also driven by mobile genetic elements but these do not by themselves explain the atypically low gene coding density found in this species. The remarkable genome conservation despite the presence of active systems for genome rearrangement implies both an efficient global dispersal system, and a high selective fitness for this species

Free energy for parameterized Polyakov loops in SU(2) and SU(3) lattice gauge theory

We present a study of the free energy of parameterized Polyakov loops P in SU(2) and SU(3) lattice gauge theory as a function of the parameters that characterize P. We explore temperatures below and above the deconfinement transition, and for our highest temperatures T > 5 T_c we compare the free energy to perturbative results.Comment: Minor changes. Final version to appear in JHE