Retrace error calibration for interferometric measurements using an unknown optical system.

In classical interferometric null test measurements, the measurement and reference beam path should be the same. A difference in the beam paths results in the so called retrace error. One very common approach to avoid retrace errors is to adapt the measurement wavefront to the reference wavefront with a computer generated hologram (CGH), which is costly and time consuming. A much more flexible approach is to do non nulltest measurement in combination with mathematical treatment of retrace errors. Most of such methods are based on iterative optimization or calibration of the nominal optical design of the interferometer. While this may be a convenient solution in the context of research, the more common use may be limited due to the need of the optical design of all interferometer components. In many cases, the optical designs of standard off the shelf optical assemblies are not available or disclosed by the manufacturer. This is especially true for transmission spheres of interferometers. We introduce the so called Black Box Model (BBM), used in the well known Tilted Wave Interferometry (TWI), as a mathematical model to account for retrace errors in interferometry. The Black Box Model is based on point characteristic functions which are adapted to the result and behavior of a real interferometer by calibration. With an extended calibration method, the need of a specific optical design of the interferometer is no longer necessary. Thus the method is attractive for a wide field of use in interferometry with standard off the shelf components.

Interferometric radius of curvature measurements: an environmental error treatment.

Interferometric determination of sphere radii is a well known technique. To keep accuracy high and uncertainties low, a precisely controlled environment is usually necessary. Environmental changes in temperature lead to time dependent drift in important measurement parameters and to disturbed results. We present a method to minimize time dependent drift to the first order. With this method, it is either possible to reduce the uncertainties further, or to relax environmental conditions and still be able to accomplish high precision measurements. We discuss two typical measurement configurations, the associated benefits and drawbacks and some relevant error sources.

Phase errors in high line density CGH used for aspheric testing: beyond scalar approximation.

One common way to measure asphere and freeform surfaces is the interferometric Null test, where a computer generated hologram (CGH) is placed in the object path of the interferometer. If undetected phase errors are present in the CGH, the measurement will show systematic errors. Therefore the absolute phase of this element has to be known. This phase is often calculated using scalar diffraction theory. In this paper we discuss the limitations of this theory for the prediction of the absolute phase generated by different implementations of CGH. Furthermore, for regions where scalar approximation is no longer valid, rigorous simulations are performed to identify phase sensitive structure parameters and evaluate fabrication tolerances for typical gratings.

Use of a mouse model to elucidate the phenotypic effects of the von Willebrand factor cleavage mutants, Y1605A/M1606A and R1597W.

BACKGROUND: von Willebrand Factor (VWF) is tightly regulated by the metalloproteinase ADAMTS13, which cleaves VWF to reduce VWF multimer size and binding affinity for collagen and platelets. OBJECTIVE: This study examines two VWF mutations, R1597W (enhanced cleavage) and Y1605A-M1606A (decreased cleavage), to determine their impact on VWF, in addition to ADAMTS13-mediated cleavage. METHODS: In vitro mouse ADAMTS13 digestions were performed on recombinant proteins. VWF knockout mice received hydrodynamic injections of mouse Vwf cDNA, following which VWF antigen, multimer profile and VWF propeptide levels were determined. A ferric chloride injury model of thrombosis was also evaluated. RESULTS: In vitro ADAMTS13 digestion of full-length mouse VWF required > 97-fold higher ADAMTS13 levels for Y1605A/M1606A, and 68% lower ADAMTS13 levels for R1597W compared with wild type. In vivo, R1597W had reduced VWF:Ag and both mutations exhibited increased VWF propeptide/VWF:Ag ratios. R1597W multimers show a lower molecular weight profile compared with wild type and Y1605A/M1606A mice. When co-injected with Adamts13 cDNA, Y1605A/M1606A multimers were larger compared with wild type, and R1597W showed only a single multimer band and decreased clearance via VWFpp/VWF:Ag ratio. R1597W was associated with reduced thrombus formation but normal platelet accumulation in a ferric chloride injury model while Y1605A/M1606A had a loss of occlusive thrombi but increased platelet accumulation compared with wild type. CONCLUSIONS: This study demonstrates that mutations that alter ADAMTS13 cleavage also can affect VWF clearance, VWF antigen level, multimer structure and thrombotic potential in the VWF knockout hydrodynamic injection model.

The effect of exercise on von Willebrand factor and ADAMTS-13 in individuals with type 1 and type 2B von Willebrand disease.

BACKGROUND: The effect of exercise on von Willebrand factor (VWF) and ADAMTS-13 levels in individuals with von Willebrand disease (VWD) has never been reported. OBJECTIVES: The aim was to quantify the effect of a standardized exercise protocol on individuals with type 1 and type 2B VWD. PATIENTS/METHODS: Thirty individuals from three groups (10 controls, 11 with type 1 VWD and 9 with type 2B VWD) completed the Standard Bruce Protocol Treadmill Test. A bleeding questionnaire was administered and blood tests were performed pre- and immediately postexercise. The groups were well matched for age, gender and body mass index (BMI). RESULTS: There was a correlation in all groups between the metabolic equivalents (METS) achieved and the degree of change of VWF and FVIII:C levels (P < 0.002, Pearson's correlation). There was a significant postexercise increase in VWF:Ag, VWF:RCo, FVIII:C and activated VWF levels in both the control group and in the type 2B VWD group, but not in the type 1 VWD group. Specific to the type 2B VWD group was an increase in the percentage of high molecular weight multimers (P = 0.022), a decrease in the mean platelet count compared with the other groups (P < 0.001) and an increase in the ADAMTS-13 level (P = 0.001). CONCLUSIONS: There are significant differences in the effects of exercise on individuals with type 1 and type 2B VWD compared with controls. Further clinical studies are necessary to evaluate exercise as a therapeutic option in VWD.

Modulation of articular chondrocyte proliferation and anionic glycoconjugate synthesis by glucosamine (GlcN), N-acetyl GlcN (GlcNAc) GlcN sulfate salt (GlcN.S) and covalent glucosamine sulfates (GlcN-SO4).

OBJECTIVES: To investigate, in chondrocyte cultures under conditions for maximizing responses in proliferation and proteoglycan (PG) synthesis, the effects of glucosamine hydrochloride (GlcN.HCl) and glucosamine sulfate (GlcN.S) salts, N-acetyl glucosamine (GlcNAc), and covalently substituted GlcN-X,Y,Z(SO(4))(n) (general formula). METHODS: Bovine articular chondrocytes (BAC) were studied under anchorage-independent (AI, alginate beads) and anchorage-dependent (AD, plastic surface) conditions. Differentiation markers were evaluated (e.g., cartilage-specific (V+C)(-) fibronectin). Varying concentrations of GlcN.HCl, GlcN.S, GlcNAc and GlcN sulfated at positions -2, -3, -6, (-2,3), (-3,6) and (-3,4,6), were tested. Cell proliferation, DNA synthesis and [(35)S]-sulfate incorporation into newly synthesized PG were determined. RESULTS: Increasing GlcN.HCl or GlcN.S concentrations gave decreasing net PG synthesis. Compounds showed more pronounced effects in AD cultures (expressing the V(-)C(+) fibronectin isoform) compared to AI cultures ((V+C)(-) isoform). Addition of GlcN.HCl or GlcN.S gave a concentration-dependent decrease in BAC proliferation, partially prevented by glucose (Glc). GlcNAc was not inhibitory. Addition of GlcN-2-SO(4) or GlcN-2,6-diSO(4) did not affect proliferation or DNA synthesis. The other GlcN-sulfates gave varying inhibitory effects, which for GlcN-3-SO(4) were reversed by inosine. CONCLUSIONS: The free amino group of GlcN seems responsible for inhibition of chondrocyte proliferation and PG synthesis. These effects were greater under higher concentrations of GlcN in AD vs AI conditions. GlcN.HCl behaves similarly to GlcN.S, but differential effects with GlcN-X,Y,Z(SO(4))(n) isomers were observed. Acetylation or sulfation of the GlcN amino group reverses or partially reverses, respectively, anti-proliferative effects of GlcN. Sulfation of GlcN, at positions 3 and 6 results in complex effects on AC proliferation and PG synthesis.

Introduction and expression of the bacterial glyoxylate cycle genes in transgenic mice.

The glyoxylate cycle, catalysed by two unique enzymes: isocitrate lyase (ICL; EC 4.1.3.1) and malate synthase (MS; EC 4.1.3.2), is necessary for the net conversion of acetate into glucose. This metabolic pathway operates in microorganisms, higher plants and nematodes. Two bacterial genes, encoding ICL and MS, were modified in order to introduce them into the mouse germ line. The ovine metallothionein-Ia (MT-Ia) promoter-ace B gene-ovine growth hormone (GH) gene (3' GH sequence) construct was fused to the ovine, MT-Ia promoter-ace A gene-ovine GH gene (3' GH sequence). Therefore, in this single DNA sequence, both ace A and ace B are under independent MT-Ia promoter control and can be induced by zinc. Transgenic mice were generated by pronuclear microinjection of the ace B-ace A gene construct. We now report the establishment of four mouse lines carying these two transgenes. Studies on the progeny of these lines indicate that one line (No. 91) is expressing both genes at the mRNA and enzyme levels in the liver and intestine, whereas another line (No. 66) has a much lower expression. Both enzyme activities were detected in the liver and intestine at levels up to 25% of those measured in fully derepressed Escherichia coli cells.