Pseudohypocalcemia caused by perchlorate (Irenat (R))

Background: Blood gas analysis (BGA), including measurement of ionized calcium, is performed routinely in patients with end stage renal disease on renal replacement therapy, especially when using citrate for regional anticoagulation. After installation of a new blood gas analyzer (RAPIDpoint (R) 405; BGA), we observed lower ionized calcium concentrations in a few patients without signs of hypocalcemia, whereas calcium concentrations were normal using a standard laboratory method. Pseudohypocalcemia was of limited duration and correlated with the short-term intake of sodium perchlorate monohydrate (Irenat (R)). Methods: We prepared dilution series from whole blood samples and stock solutions of calcium and perchlorate with different concentrations of ionized calcium and perchlorate. Measurement of ionized calcium concentrations was performed using two different blood gas analyzers (RAPIDpoint (R) 405; BGA and Roche AVL 9180; standard laboratory method). Results: After addition of different amounts of perchlorate, significant lower ionized calcium concentrations were measured with BGA compared to the standard laboratory method using either preparations from whole blood samples or stock solutions. The addition of potassium or methylene blue known to complex perchlorate had no effect on the concentrations of ionized calcium measured with BGA. Using different mathematical methods, a calculation of the "real" ionized calcium concentration from the value measured with BGA was not possible. Conclusions: Based on our experiments, we confirm the hypothesis that perchlorate can influence the measurement of ionized calcium by BGA. As the effect depends on the ion selective electrode that is used, it is advisable to test the blood gas analyzer with calcium and perchlorate solutions

Numerical solution of optimal control problems with constant control delays

We investigate a class of optimal control problems that exhibit constant exogenously given delays in the control in the equation of motion of the differential states. Therefore, we formulate an exemplary optimal control problem with one stock and one control variable and review some analytic properties of an optimal solution. However, analytical considerations are quite limited in case of delayed optimal control problems. In order to overcome these limits, we reformulate the problem and apply direct numerical methods to calculate approximate solutions that give a better understanding of this class of optimization problems. In particular, we present two possibilities to reformulate the delayed optimal control problem into an instantaneous optimal control problem and show how these can be solved numerically with a state-of-the-art direct method by applying Bock’s direct multiple shooting algorithm. We further demonstrate the strength of our approach by two economic examples.delayed differential equations, delayed optimal control, numerical optimization, time-to-build

Numerical Solution of Optimal Control Problems with Constant Control Delays

We investigate a class of optimal control problems that exhibit constant exogenously given delays in the control in the equation of motion of the differential states. Therefore, we formulate an exemplary optimal control problem with one stock and one control variable and review some analytic properties of an optimal solution. However, analytical considerations are quite limited in case of delayed optimal control problems. In order to overcome these limits, we reformulate the problem and apply direct numerical methods to calculate approximate solutions that give a better understanding of this class of optimization problems. In particular, we present two possibilities to reformulate the delayed optimal control problem into an instantaneous optimal control problem and show how these can be solved numerically with a state-of-the-art direct method by applying Bock's direct multiple shooting algorithm. We further demonstrate the strength of our approach by two economic example

IL-2 receptor α chain (CD25JAC) expression defines a crucial stage in pre-B cell development

The analysis of the expression of the a chain of the IL-2 receptor (CD25.TAC) on the surface of B lineage cells In mouse bone marrow reveals that it is a useful marker to distinguish pre-B-I from pre-B-II cells. CD25 Is not expressed on CD45R(B220)+ c-kit+ CD43+ TdT+ λ5+ Cμ− slg− lgH chain locus DJH-rearranged pre-B-I cells of mouse bone marrow. It is expressed on large cycling CD45R(B220)+ c-kit+ CD43+ TdT+ λ5+ Cμ− sig− and on small resting CD45R(B220)+ c-kit+ CD43− TdT+ λ5+ Cμ− sig− sig- IgH chain locus VHDJH-rearranged pre-B-II cells. Therefore, the transition from pre-B-I to large pre-B-II cells is marked by the downregulation of c-kit and terminal deoxynucleotldyl transferase (TdT), and by the upregulatton of CD25. SCID, RAG-2T, μMT and γ6T mutant mice do have normal, If not elevated numbers of pre-B-I cells but lack all CD25+ pre-B-II cells in their bone marrow. The expression of a transgenic H chain under control of the μH chain enhancer in RAG-2T bone marrow B lineage precursors allows the development of large and small CD25+ pre-B-II cells. The results suggest that the differentiation of pre-B-I to pre-B-II cells in mouse bone marrow requires the expression of μH chains and surrogate L chains in membranes, probably on the surface of precursor B cell

On the Transition from Instantaneous to Time-Lagged Capital Accumilation: The Case of Leontief Type Production Functions

We formulate an optimal control capital accumulation model with a Leontief-type production function and an exogenously given time-lag between investment and the accumulation of the capital stock, to analyze the qualitative and quantitative influence of time-lags on the system dynamics. As known from the time-to-build literature, optimal investment paths for positive and finite time-lags are in general cyclical, in contrast to the monotonic optimal paths for instantaneous capital accumulation. We show that the transition between instantaneous and time-lagged capital accumulation is continuous, in the sense that the greater is the time-lag between investment and capital accumulation, the more likely and more pronounced becomes cyclical behavior of the optimal paths. --cyclical optimal paths,numerical optimization,time-lagged optimal control,time-to-build

The Geometry of the Catalytic Active Site in [FeFe]-hydrogenases is Determined by Hydrogen Bonding and Proton Transfer

[FeFe]-hydrogenases are efficient metalloenzymes that catalyze the oxidation and evolution of molecular hydrogen, H2. They serve as a blueprint for the design of synthetic H2-forming catalysts. [FeFe]-hydrogenases harbor a six-iron cofactor that comprises a [4Fe-4S] cluster and a unique diiron site with cyanide, carbonyl, and hydride ligands. To address the ligand dynamics in catalytic turnover and upon carbon monoxide (CO) inhibition, we replaced the native aminodithiolate group of the diiron site by synthetic dithiolates, inserted into wild-type and amino acid variants of the [FeFe]-hydrogenase HYDA1 from Chlamydomonas reinhardtii. The reactivity with H2 and CO was characterized using in situ and transient infrared spectroscopy, protein crystallography, quantum chemical calculations, and kinetic simulations. All cofactor variants adopted characteristic populations of reduced species in the presence of H2 and showed significant changes in CO inhibition and reactivation kinetics. Differences were attributed to varying interactions between polar ligands and the dithiolate head group and/or the environment of the cofactor (i.e., amino acid residues and water molecules). The presented results show how catalytically relevant intermediates are stabilized by inner-sphere hydrogen bonding suggesting that the role of the aminodithiolate group must not be restricted to proton transfer. These concepts may inspire the design of improved enzymes and biomimetic H2-forming catalysts