Characterization of amyloidogenic immunoglobulin light chains directly from serum by on-line immunoaffinity isolation

Primary systemic amyloidosis (AL) is characterized by the overproduction of immunoglobulin light chain proteins by a monoclonal, terminally differentiated B-lymphocyte or plasma cell clone. The free immunoglobulin light chains are deposited in an abnormal conformation as amyloid in a variety of organs in the body. The mechanism of amyloid formation is not well understood, but appears to be associated with some form of cleavage of the immunoglobulin light chain with subsequent aggregate formation. In an attempt to characterize the structure of amyloid-forming light chain proteins we developed an on-line immunoaffinity purification and subsequent characterization of free kappa and free lambda immunoglobulin light chains by electrospray ionization mass spectrometry. The methodology is totally automated and requires 20 micro L of serum. Mass spectral analysis of Bence Jones proteins under non-denaturing conditions was also utilized to examine the tertiary and quaternary structure of light chain proteins and clearly shows covalent dimer formation of lambda type light chain. This type of on-line assay may prove helpful in elucidating distinguishing features capable of discriminating AL from benign monoclonal gammopathies of undetermined significance as well as diagnosing AL.     

Cytotoxicity and Antiproliferative Effect of Hypericin and Derivatives after Photosensitization

The toxicity on three human tumor cell lines (A431, HeLa and MCF7) of five phenanthroperylenequinones (hypericin and derivatives) and two perylenequinones (cercosporin and calphostin C) was investigated after photosensitization (4 J/cm²). Furthermore, the antiproliferative effect on HeLa cells was studied for the phenanthroperylenequinones. Hypericin, 2,5-dibromohypericin, 2,5,9,12-tetrabromohypericin and perylenequinones displayed a potent cytotoxic and antiproliferative effect in the nanomolar range. Hypericin dicarboxylic acid exhibited no photoactivity. In general, the antiproliferative activity correlated well with the photocytotoxicity. However, the nonphotocytotoxic compound hexamethylhypericin showed potent antiproliferative activity in the nanomolar range, probably exerting its action by protein kinase C inhibition. Without light irradiation, no cytotoxic and antiproliferative effect was observed for any photocytotoxic phenanthroperylenequinone compound. Furthermore, confocal laser microscopy revealed that the subcellular localization in A431 cells was similar for the photoactive compounds; the photosensitizers were mainly concentrated in the perinuclear region, probably corresponding with the Golgi apparatus and the endoplasmic reticulum. In addition, the accumulation of the photosensitizers in HeLa cells was investigated. All compounds except hypericin dicarboxylic acid were found to concentrate to a large extent in the cells. The compound 2,5,9,12-tetrabromohypericin seemed intrinsically more effective than hypericin since the intracellular concentration of the bromoderivative was a magnitude of order lower than that of hypericin although both compounds showed similar photobiological activity.     

Single molecule spectroscopy as a probe for dye-polymer interactions

Experimental (Single Molecule Spectroscopy) and theoretical (quantum-chemical calculations and Monte Carlo and molecular dynamics simulations) techniques are combined to investigate the behavior and dynamics of a polymer-dye molecule system. It is shown that the dye molecule of interest (1,1'-dioctadecyl-3,3,3',3'-tetramethylindo-dicarbocyanine) adopts two classes of conformations, namely planar and nonplanar ones, when embedded in a poly(styrene) matrix. From an in-depth analysis of the fluorescence lifetime trajectories, the planar conformers can be further classified according to the way their alkyl side chains interact with the surrounding poly(styrene) chains.     

Influence of geography on language competition

Competition between languages or cultural traits diffusing in the same geographical area is studied combining the model of Abrams and Strogatz with a model of human dispersal on an inhomogeneous substrate. Also, the effect of population growth is discussed. It is shown through numerical simulations that the final configuration of the languages can be strongly affected by geographical and historical factors. These factors are not related to the dynamics of culture transmission, but rather to initial population distributions as well as geographical boundaries and inhomogeneities, which modulate the diffusion process.     

Pulsed electron-electron double resonance on multinuclear metal clusters: assignment of spin projection factors based on the dipolar interaction

The interaction between two paramagnetic metal centers, a [3Fe-4S](+) cluster and a [NiFe] center, is investigated in the hydrogenase from Desulfovibrio vulgaris Miyazaki F by pulsed ELDOR (electron-electron double resonance). The distance between the metal centers is known from X-ray crystallography. The experimental dipolar spin-spin interaction deviates from the value expected for two point-dipoles located at the centers of the metal clusters. An extended spin-coupling model accounting for the spin coupling in the [3Fe-4S](+) cluster yields the observed interaction under the assumption of a particular magnetic coupling scheme for the three Fe ions. These results demonstrate that pulsed ELDOR can be used to gain insight into the inner structure of a multinuclear metal cluster.     

Synchronization of chaotic semiconductor laser systems: a vectorial coupling-dependent scenario

We demonstrate the influence of vectorial coupling on the synchronization behavior of complex systems. We study two semiconductor lasers subject to delayed optical feedback which are unidirectionally coherently coupled via their optical fields. Our experimental and numerical results demonstrate a characteristic synchronization scenario in dependence on the relative feedback phase leading cyclically from chaos synchronization to almost uncorrelated states, and back to chaos synchronization. Finally, we reveal the influence of the feedback phase on the dynamics of the solitary delay system.     

Skew Derivations with Central Invariants

If is an automorphism and is a -derivation of a ring R, thenthe subring of invariants is the set R⁽⁾={rR|(r)=0}. The mainresult of this paper is ‘let R be a semiprime ring withan algebraic -derivation such that R⁽⁾ is central; then R iscommutative’. This theorem generalizes results on theinvariants of automorphisms and derivations and is proved byreducing down to the special cases of automorphisms and derivations.     

Resonant-cavity light-emitting diodes: quantum noise and spatial emission characteristics

We demonstrate the interplay between the intensity noise and the spatial emission characteristics of resonant-cavity light-emitting diodes. First, we find that the total aperture intensity noise exhibits a sub-shot noise behavior in a quite large pumping regime. Second, we investigate the angular, spectral, and spatial emission characteristics of the devices by controlling the shape and width of the angular intensity distribution via temperature detuning of the quantum well wavelength and the cavity resonance wavelength. Finally, the angular and aperture resolved intensity noise exhibit a super-shot noise behavior in contrast to that of the total emission. We explain this difference with anticorrelations between various radial components which increase with the temperature-tuned extension of the spatial emission. PACS 85.60.Jb; 42.50.L; 23.20.En