Neural crest cell-autonomous roles of fibronectin in cardiovascular development.

The chemical and mechanical properties of extracellular matrices (ECMs) modulate diverse aspects of cellular fates; however, how regional heterogeneity in ECM composition regulates developmental programs is not well understood. We discovered that fibronectin 1 (Fn1) is expressed in strikingly non-uniform patterns during mouse development, suggesting that regionalized synthesis of the ECM plays cell-specific regulatory roles during embryogenesis. To test this hypothesis, we ablated Fn1 in the neural crest (NC), a population of multi-potent progenitors expressing high levels of Fn1. We found that Fn1 synthesized by the NC mediated morphogenesis of the aortic arch artery and differentiation of NC cells into vascular smooth muscle cells (VSMCs) by regulating Notch signaling. We show that NC Fn1 signals in an NC cell-autonomous manner through integrin α5β1 expressed by the NC, leading to activation of Notch and differentiation of VSMCs. Our data demonstrate an essential role of the localized synthesis of Fn1 in cardiovascular development and spatial regulation of Notch signaling

Stabilizing Quantum States by Constructive Design of Open Quantum Dynamics

Based on recent work on the asymptotic behavior of controlled quantum Markovian dynamics, we show that any generic quantum state can be stabilized by devising constructively a simple Lindblad-GKS generator that can achieve global asymptotic stability at the desired state. The applications of such result is demonstrated by designing a direct feedback strategy that achieves global stabilization of a qubit state encoded in a noise-protected subspace.Comment: Revised version with stronger proofs showing uniqueness can be achieved in all cases by using the freedom to the choose diagonal elements of both the Hamiltonian and Lindblad operator, and exploiting the fact that the non-existence of two orthogonal eigenvectors of the Lindblad operator is sufficient but not necessary for global asymptotic stability of the target stat

Global Control Methods for GHZ State Generation on 1-D Ising Chain

We discuss how to prepare an Ising chain in a GHZ state using a single global control field only. This model does not require the spins to be individually addressable and is applicable to quantum systems such as cold atoms in optical lattices, some liquid- or solid-state NMR experiments, and many nano-scale quantum structures. We show that GHZ states can always be reached asymptotically from certain easy-to-prepare initial states using adiabatic passage, and under certain conditions finite-time reachability can be ensured. To provide a reference useful for future experimental implementations three different control strategies to achieve the objective, adiabatic passage, Lyapunov control and optimal control are compared, and their advantages and disadvantages discussed, in particular in the presence of realistic imperfections such as imperfect initial state preparation, system inhomogeneity and dephasing.Comment: 13 pages, 11 figure

Symmetry & Controllability for Spin Networks with a Single-Node Control

We consider the relation of symmetries and subspace controllability for spin networks with XXZ coupling subject to control of a single node by a local potential (Z-control). Such networks decompose into excitation subspaces. Focusing on the single excitation subspace it is shown that for single-node Z-controls external symmetries are characterized by eigenstates of the system Hamiltonian that have zero overlap with the control node, and there are no internal symmetries. It is further shown that there are symmetries that persist even in the presence of random perturbations. For uniformly coupled XXZ chains a characterization of all possible symmetries is given, which shows a strong dependence on the position of the node we control. Finally, it is shown rigorously for uniform Heisenberg and XX chains subject to single-node Z-control that the lack of symmetry is not only necessary but sufficient for subspace controllability. The latter approach is then generalized to establish controllability results for simple branched networks.Comment: 11 pages, some figures. 3 tables, minor revisio

The Xenopus Suc1/Cks Protein Promotes the Phosphorylation of G2/M Regulators

The entry into mitosis is controlled by Cdc2/cyclin B, also known as maturation or M-phase promoting factor (MPF). In Xenopus egg extracts, the inhibitory phosphorylations of Cdc2 on Tyr-15 and Thr-14 are controlled by the phosphatase Cdc25 and the kinases Myt1 and Wee1. At mitosis, Cdc25 is activated and Myt1 and Wee1 are inactivated through phosphorylation by multiple kinases, including Cdc2 itself. The Cdc2-associated Suc1/Cks1 protein (p9) is also essential for entry of egg extracts into mitosis, but the molecular basis of this requirement has been unknown. We find that p9 strongly stimulates the regulatory phosphorylations of Cdc25, Myt1, and Wee1 that are carried out by the Cdc2/cyclin B complex. Overexpression of the prolyl isomerase Pin1, which binds to the hyperphosphorylated forms of Cdc25, Myt1, and Wee1 found at M-phase, is known to block the initiation of mitosis in egg extracts. We have observed that Pin1 specifically antagonizes the stimulatory effect of p9 on phosphorylation of Cdc25 by Cdc2/cyclin B. This observation could explain why overexpression of Pin1 inhibits mitotic initiation. These findings suggest that p9 promotes the entry into mitosis by facilitating phosphorylation of the key upstream regulators of Cdc2

Penalties for Emergency Medical Treatment and Labor Act Violations Involving Obstetrical Emergencies

Introduction: The Emergency Medical Treatment and Labor Act (EMTALA) was intended to prevent inadequate, delayed, or denied treatment of emergent conditions by emergency departments (ED). While controversies exist regarding the scope of the law, there is no question that EMTALA applies to active labor, a key tenet of the statute and the only medical condition – labor – specifically included in the title of the law. In light of rising maternal mortality rates in the United States, further exploration into the state of emergency obstetrical (OB) care is warranted. Understanding civil monetary penalty settlements levied by the Office of the Inspector General (OIG) related to EMTALA violations involving labor and other OB emergencies will help to inform the current state of access to and quality of OB emergency care.Methods: We reviewed descriptions of all EMTALA-related OIG civil monetary penalty settlements from 2002-2018. OB-related cases were identified using keywords in settlement descriptions. We described characteristics of settlements including the nature of the allegation and compared them with non-OB settlements.Results: Of 232 EMTALA-related OIG settlements during the study period, 39 (17%) involved active labor and other OB emergencies. Between 2002 and 2018 the proportion of settlements involving OB emergencies increased from 17% to 40%. Seven (18%) of these settlements involved a pregnant minor. Most OB cases involved failure to provide screening exam (82%) and/or stabilizing treatment (51%). Failure to arrange appropriate transfer was more common for OB  (36%) compared with non-OB settlements (21%) (p = 0.041). Fifteen (38%) involved a provider specifically directing a pregnant woman to proceed to another hospital, typically by private vehicle.Conclusion: Despite inclusion of the term “labor” in the law’s title, one in six settlements related to EMTALA violations involved OB emergencies. One in five settlements involved a pregnant minor, indicating that providers may benefit from education regarding obligations to evaluate and stabilize minors absent parental consent. Failure to arrange appropriate transfer was more common among OB settlements. Findings suggesting need for providers to understand EMTALA-specific requirements for appropriate transfer and for EDs at hospitals without dedicated OB services to implement policies for evaluation of active labor and protocols for transfer when indicated

Thermochemistry of iron manganese oxide spinels

Oxide melt solution calorimetry has been performed on iron manganese oxide spinels prepared at high temperature. The enthalpy of formation of (MnxFe1−x)3O4 at 298 K from the oxides, tetragonal Mn3O4 (hausmannite) and cubic Fe3O4 (magnetite), is negative from x=0 to x=0.67 and becomes slightly positive for 0.670.6) spinels of intermediate compositions. The enthalpies of formation are discussed in terms of three factors: oxidation–reduction relative to the end-members, cation distribution, and tetragonality. A combination of measured enthalpies and Gibbs free energies of formation in the literature provides entropies of mixing. ΔSmix, consistent with a cation distribution in which all trivalent manganese is octahedral and all other ions are randomly distributed for x>0.5, but the entropy of mixing appears to be smaller than these predicted values for x<0.4

Endothelium in the pharyngeal arches 3, 4 and 6 is derived from the second heart field.

Oxygenated blood from the heart is directed into the systemic circulation through the aortic arch arteries (AAAs). The AAAs arise by remodeling of three symmetrical pairs of pharyngeal arch arteries (PAAs), which connect the heart with the paired dorsal aortae at mid-gestation. Aberrant PAA formation results in defects frequently observed in patients with lethal congenital heart disease. How the PAAs form in mammals is not understood. The work presented in this manuscript shows that the second heart field (SHF) is the major source of progenitors giving rise to the endothelium of the pharyngeal arches 3 - 6, while the endothelium in the pharyngeal arches 1 and 2 is derived from a different source. During the formation of the PAAs 3 - 6, endothelial progenitors in the SHF extend cellular processes toward the pharyngeal endoderm, migrate from the SHF and assemble into a uniform vascular plexus. This plexus then undergoes remodeling, whereby plexus endothelial cells coalesce into a large PAA in each pharyngeal arch. Taken together, our studies establish a platform for investigating cellular and molecular mechanisms regulating PAA formation and alterations that lead to disease

The Xenopus Chk1 Protein Kinase Mediates a Caffeine-sensitive Pathway of Checkpoint Control in Cell-free Extracts

We have analyzed the role of the protein kinase Chk1 in checkpoint control by using cell-free extracts from Xenopus eggs. Recombinant Xenopus Chk1 (Xchk1) phosphorylates the mitotic inducer Cdc25 in vitro on multiple sites including Ser-287. The Xchk1-catalyzed phosphorylation of Cdc25 on Ser-287 is sufficient to confer the binding of 14-3-3 proteins. Egg extracts from which Xchk1 has been removed by immunodepletion are strongly but not totally compromised in their ability to undergo a cell cycle delay in response to the presence of unreplicated DNA. Cdc25 in Xchk1-depleted extracts remains bound to 14-3-3 due to the action of a distinct Ser-287-specific kinase in addition to Xchk1. Xchk1 is highly phosphorylated in the presence of unreplicated or damaged DNA, and this phosphorylation is abolished by caffeine, an agent which attenuates checkpoint control. The checkpoint response to unreplicated DNA in this system involves both caffeine-sensitive and caffeine-insensitive steps. Our results indicate that caffeine disrupts the checkpoint pathway containing Xchk1