Tyrosine Sulfation of Native Mouse Psgl-1 Is Required for Optimal Leukocyte Rolling on P-Selectin In Vivo

We recently demonstrated that tyrosine sulfation is an important contributor to monocyte recruitment and retention in a mouse model of atherosclerosis. P-selectin glycoprotein ligand-1 (Psgl-1) is tyrosine-sulfated in mouse monocyte/macrophages and its interaction with P-selectin is important in monocyte recruitment in atherosclerosis. However, whether tyrosine sulfation is required for the P-selectin binding function of mouse Psgl-1 is unknown. Here we test the function of native Psgl-1 expressed in leukocytes lacking endogenous tyrosylprotein sulfotransferase (TPST) activity.Psgl-1 function was assessed by examining P-selectin dependent leukocyte rolling in post-capillary venules of C57BL6 mice transplanted with hematopoietic progenitors from wild type (WT → B6) or Tpst1;Tpst2 double knockout mice (Tpst DKO → B6) which lack TPST activity. We observed that rolling flux fractions were lower and leukocyte rolling velocities were higher in Tpst DKO → B6 venules compared to WT → B6 venules. Similar results were observed on immobilized P-selectin in vitro. Finally, Tpst DKO leukocytes bound less P-selectin than wild type leukocytes despite equivalent surface expression of Psgl-1.These findings provide direct and convincing evidence that tyrosine sulfation is required for optimal function of mouse Psgl-1 in vivo and suggests that tyrosine sulfation of Psgl-1 contributes to the development of atherosclerosis

I Going Away. I Going Home. : Austin Clarke\u27s Leaving this Island Place

Austin Clarke’s “Leaving This Island Place” is one of scores of Caribbean autobiographical works that focus on a bright, young, lower-class islander leaving his/her small island place and setting out on “Eldorado voyages.” The narrative of that journey away from home to Europe or Canada or the United States and the later efforts to return may be said to be the Caribbean story, as suggested in the subtitle of Wilfred Cartey’s study of Caribbean literature, Whispers from the Caribbean: I Going Away, I Going Home, which argues that while in Caribbean literature there is much movement away, there is also a body of literature in which “the notion of ‘away’ and images of movement out are replaced by images of return” (xvi). Traditionally, however, the first autobiographical works, such as George Lamming’s In the Castle of My Skin, V. S. Naipaul’s A House for Mr. Biswas, Merle Hodge’s Crick Crack, Monkey, Jamaica Kincaid’s Annie John, Michelle Cliff’s No Telephone to Heaven, Edwidge Danticat’s Breath, Eyes, Memory, and Elizabeth Nunez’s Beyond the Limbo Silence, have focused on the childhood in the Caribbean and the journey away—or at least the preparation for that journey. Such is the case with Clarke’s “Leaving This Island Place.

Frailty in primary care: a review of its conceptualization and implications for practice

Frail, older patients pose a challenge to the primary care physician who may often feel overwhelmed by their complex presentation and tenuous health status. At the same time, family physicians are ideally suited to incorporate the concept of frailty into their practice. They have the propensity and skill set that lends itself to patient-centred care, taking into account the individual subtleties of the patient's health within their social context. Tools to identify frailty in the primary care setting are still in the preliminary stages of development. Even so, some practical measures can be taken to recognize frailty in clinical practice and begin to address how its recognition may impact clinical care. This review seeks to address how frailty is recognised and managed, especially in the realm of primary care

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Search for strange-pentaquark production in e(+)e(-) annihilation at root s=10.58 GeV

We search for strange-pentaquark states that have been previously reported by other experiments-the Theta(1540)(+), Xi(5)(1860)(--), and Xi(5)(1860)(0)-in 123 fb(-1) of data recorded with the BABAR detector at the PEP-II e(+)e(-) storage ring. We find no evidence for these states and set 95% confidence level upper limits on the number of Theta(1540)(+) and Xi(5)(1860)(--) pentaquarks produced per e(+)e(-) annihilation into q (q) over bar and per Upsilon(4S) decay. For q (q) over bar events the Theta(1540)(+) [Xi(5)(1860)(--)] limit is about 8 [4] times lower than the rates measured for ordinary baryons of similar mass

Numerical Optimal Control Of Parabolic PDEs Using DASOPT

. This paper gives a preliminary description of DASOPT, a software system for the optimal control of processes described by time-dependent partial differential equations (PDEs). DASOPT combines the use of efficient numerical methods for solving differential-algebraic equations (DAEs) with a package for large-scale optimization based on sequential quadratic programming (SQP). DASOPT is intended for the computation of the optimal control of time-dependent nonlinear systems of PDEs in two (and eventually three) spatial dimensions, including possible inequality constraints on the state variables. By the use of either finite-difference or finite-element approximations to the spatial derivatives, the PDEs are converted into a large system of ODEs or DAEs. Special techniques are needed in order to solve this very large optimal control problem. The use of DASOPT is illustrated by its application to a nonlinear parabolic PDE boundary control problem in two spatial dimensions. Computational resu..