Fluorescence-based single-strand conformation polymorphism analysis of mutations by capillary electrophoresis

Capillary electrophoresis in combination with fluorescence-based single-strand conformation polymorphism (SSCP) analysis was used to screen for known mutations as well as for unknown mutations. The mutations causing hemochromatosis and thrombogenetic diseases (factor V Leiden mutation and prothrombin mutation) are well defined. Familial hypercholesterolemia is caused by mutations in the low density lipoprotein (LDL) receptor gene. Because the mutations are heterogeneously localized in all 18 exons of the LDL receptor gene, effective screening procedures are necessary. The three well known mutations and 59 of 61 previously characterized mutations in the LDL receptor gene were detected by a distinct abnormal fragment pattern in capillary electrophoresis. The remaining two mutations in the LDL receptor gene showed only slight abnormalities under standard electrophoresis conditions (13 kV, 30 degrees C, 30 min). However, the abnormal pattern could be amplified by increasing the electrophoresis temperature. In all cases, heterozygous and homozygous mutations could clearly be differentiated from wild-type alleles. Because of the high efficiency of mutation detection, capillary electrophoresis in combination with fluorescence-based SSCP analysis would be attractive for the detection of well-defined mutations as well as for the screening of unknown mutations. The accuracy and the degree of automation make this technique well suited for routine genetic diagnosis.     

An approximate method for calculating depletion and structural interactions between colloidal particles

An approximate method is evaluated for calculating the second virial coefficient in a dilute macromolecular solution bounded by two interfaces. The approximation is essentially the superposition of the coefficients calculated independently for each surface. To test this approach, the depletion interaction between two particles in a solution of nonadsorbing, spherical macromolecules is calculated in systems with either hard-wall or long-range electrostatic interactions. In all systems tested, the interparticle interaction energy calculated with the approximation is found to be in good agreement with that calculated using the exact approach (e.g., error less than 2% at the smallest separations). The primary advantage of this approximation is a significant reduction in the computation time required for calculating the depletion interaction, especially in charged systems. The paper also shows that the expressions for predicting the depletion interaction in purely hard-sphere systems can be used in dilute ionic systems, provided the appropriate effective macromolecule size is used. For the attractive depletion interaction, this effective size is determined by the range of the particle-macromolecule interaction (as opposed to the macromolecule-macromolecule interaction).     

Enhancement of blood-tumor barrier permeability by Sar-[D-Phe8]des-Arg9BK,a metabolically resistant bradykinin B1 agonist,in a rat C6 glioma model

Background

While it is well known that bradykinin B2 agonists increase plasma protein extravasation (PPE) in brain tumors, the bradykinin B1 agonists tested thus far are unable to produce this effect. Here we examine the effect of the selective B1 agonist bradykinin (BK) Sar-[D-Phe8]des-Arg9BK (SAR), a compound resistant to enzymatic degradation with prolonged activity on PPE in the blood circulation in the C6 rat glioma model.

Results

SAR administration significantly enhanced PPE in C6 rat brain glioma compared to saline or BK (p < 0.01). Pre-administration of the bradykinin B1 antagonist [Leu8]-des-Arg (100 nmol/Kg) blocked the SAR-induced PPE in the tumor area.

Conclusions

Our data suggest that the B1 receptor modulates PPE in the blood tumor barrier of C6 glioma. A possible role for the use of SAR in the chemotherapy of gliomas deserves further study.

     

Measurement and folding-potential analysis of the elastic α-scattering on light nuclei

Differential cross sections ofα-elastic scattering have been measured for the target nuclei¹¹B,¹²C,¹³C,¹⁴N,¹⁵N, and¹⁶O atE=48.7 and 54.1 MeV and for the nuclei¹⁷O,¹⁸O, and²⁰Ne atE=54.1 MeV. The experimental results were analysed in terms of the optical model using different complex potentials. Special emphasis is given to the application of the double-folding approach for the real part of the potential. The imaginary part is expressed in terms of Fourier-Bessel functions. Differential cross sections for theα-¹⁶O scattering over a wide energy range and for the elasticα-scattering for nuclei in the mass rangeA=11 up toA=24 atE=54.1 MeV are analysed by this method. A close correlation between the absorptive part of the potential and nuclear deformation is observed.     

Lewis and mediated α-alkylation of ketones using SN1 reactive alkylating agents

Alkylation of ketones via silyl enol ethers is possible using aryl activated secondary alkyl halides or thio ketals. In case of prenyl halides the ratio fo primary to tertiary alkylation is governed by steric factors and by the nature of the Lewis acid.     

Best Approximation by Free Knot Splines

We consider the problem of finding the best (uniform) approximation of a given continuous function by spline functions with free knots. Our approach can be sketched as follows. By using the Gauß transform with arbitrary positive real parameter t, we map the set of splines under consideration onto a function space, which is arbitrarily close to the spline set, but satisfies the local Haar condition and also possesses other nice structural properties. This enables us to give necessary and sufficient conditions for best approximations (in terms of alternants) and, under some assumptions, even full characterizations and a uniqueness result. By letting t 0, we recover best approximation in the original spline space. Our results are illustrated by some numerical examples, which show in particular the nice alternation behavior of the error function.     

Influence of the 61 S 0–63 P 1 resonance on continuous Lyman-α generation in mercury

Continuous coherent radiation in the vacuum ultraviolet at 122 nm (Lyman-α) can be generated using sum-frequency mixing of three fundamental laser beams in mercury vapor. One of the fundamental beams is at 254 nm wavelength, which is close to the 6¹ S ₀–6³ P ₁ resonance in mercury. Experiments have been performed to investigate the effect of this one-photon resonance on phase-matching, absorption and the nonlinear yield. The efficiency of continuous Lyman-α generation has been improved by a factor of 4.5.     

A reliable cw Lyman-α laser source for future cooling of antihydrogen

We demonstrate a reliable continuous-wave (cw) laser source at the 1 S–2 P transition in (anti)hydrogen at 121.56 nm (Lyman-α) based on four-wave sum-frequency mixing in mercury. A two-photon resonance in the four-wave mixing scheme is essential for a powerful cw Lyman-α source and is well investigated.