On the dynamics of the electric field induced breakdown in lipidmembranes

Electric field methods are powerful tools for cell characterization and manipulation. Important biotechnological applications, e.g., electrofusion of cells or electroinjection of macromolecules into living cells, rely on membrane breakdown. Despite the widespread use of these techniques, the process of membrane breakdown is poorly understood: a better understanding can be expected to lead to higher efficiencies. The present study used planar lipid bilayers in order to limit the number of experimental parameters. Membrane rupture was induced by careful application of short electric field pulses: measurement of the subsequent increase in membrane conductivity with time permitted the underlying mechanism to be characterized. The initial process of pore formation starts a few μs after the onset of the pulse, and the ensuing breakdown of the entire lipid membrane occurs within about a millisecond (pore widening velocity of a few cm/s). The kinetics of the pore-opening process could be influenced qualitatively by adding surfactants and lipid-attached macromolecules, respectively. Changing the effective mass per unit area of membrane, which could be brought about by using known percentages of lipids with covalently bound, hydrophilic polymers, allowed a model for the pore widening process to be quantitatively tested     

Efficient Er:YAG laser operating at 1645 and 1617 nm

A 1534-nm fiber laser pumped Er:YAG laser action at room temperature has been demonstrated with high efficiency at two emission wavelengths: 1645 and 1617 nm. Multiwatt continuous-wave power was demonstrated at both wavelengths and active electrooptic Q-switch operation with >90% Q-switch efficiency was achieved at 1645 nm. Etalon tuned wavelength selection showed excellent agreement with theoretical analysis.     

Evaluation of the Short Parkinson's Evaluation Scale: a new friendly scale for the evaluation of Parkinson's disease in clinical drug trials

The extensive use of the Unified Parkinson's Disease Rating Scale (UPDRS) has revealed low interrater reliability in some items and redundancy in others. In view of these shortcomings, we have structured a new scale that includes a zero-to three-point scale for each item in the evaluation of PD. The mental axis includes memory, thought disorders, and depression. Activities of daily living (ADL) includes eight items: speech, eating, feeding, dressing, hygiene, handwriting, walking, and turning in bed. The motor examination includes eight items: speech, tremor, rest and posture, rigidity, finger tapping, arising from chair, gait, and postural stability. Complications of therapy were also included: dyskinesias, dystonia, motor fluctuations, and freezing episodes, collected by history. In addition, a global scoring for motor fluctuations that should complement the Hoehn and Yahr Scale was incorporated. In this report, we present a statistical analysis of the ADL, motor evaluation, and complications of therapy sections. Concerning the interrater reliability mean, Kendall's W values were >0.9 for most of the items in the Short Parkinson's Evaluation Scale (SPES). Kendall's W <0.8 (motor evaluation) was found for two items of the SPES and nine items of the UPDRS. The mean interrater reliability for both scales across all seven centers (seven Kendall's W for seven centers) (Mann-Whitney test) showed no statistical differences between the scales. Spearman's correlations between items of both scales were significant. Factor analysis of the SPES and UPDRS data revealed a four-factor solution that explained approximately 60% of the data. All participating centers found the SPES easier to apply and quicker to complete, when compared with the UPDRS. The results obtained strongly favor the introduction of SPES for clinical practice.     

Interaction in polymer blends via dilute solution light-scattering under optical θ-conditions

Summary It is demonstrated that dilute solution light —scattering experiments under ‘optical θconditions’ offer rapid and reliable judgement of the interaction parameters in polymer blends. This has been verified with miscible blends of polystyrene with poly(vinylmethylether) and with the immiscible pair polystyrene —poly(vinylisobutylether). The capabilities of the optical θ-approach in order to derive the influence of polymerpolymer interaction on chain dimensions are discussed shortly. Herrn Dr. B. Sedlacec zu seinem 60. Geburtstag herzlichst gewidmet     

Refining Genotypes and Phenotypes in KCNA2-Related Neurological Disorders

Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel K_v1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. In addition, individuals with a milder course of epilepsy, complicated hereditary spastic paraplegia, and episodic ataxia have been reported. By analyzing phenotypic, functional, and genetic data from published reports and novel cases, we refine and further delineate phenotypic as well as functional subgroups of KCNA2-associated disorders. Carriers of variants, leading to complex and mixed channel dysfunction that are associated with a gain- and loss-of-potassium conductance, more often show early developmental abnormalities and an earlier onset of epilepsy compared to individuals with variants resulting in loss- or gain-of-function. We describe seven additional individuals harboring three known and the novel KCNA2 variants p.(Pro407Ala) and p.(Tyr417Cys). The location of variants reported here highlights the importance of the proline(405)–valine(406)–proline(407) (PVP) motif in transmembrane domain S6 as a mutational hotspot. A novel case of self-limited infantile seizures suggests a continuous clinical spectrum of KCNA2-related disorders. Our study provides further insights into the clinical spectrum, genotype–phenotype correlation, variability, and predicted functional impact of KCNA2 variants.     

Synthesis and glutathione S-transferase structure-affinity relationships of nonpeptide and peptidase-stable glutathione analogues

A series of nonpeptidic glutathione analogues where the peptide bonds were replaced by simple carbon-carbon bonds or isosteric E double bonds were prepared. The optimal length for the two alkyl chains on either side of the mercaptomethyl group was evaluated using structure-affinity relationships. Affinities of the analogues 14a-f, 23, and 25 were evaluated for a recombinant GST enzyme using a new affinity chromatography method previously developed in our laboratory. Analysis of these analogues gives an additional understanding for GST affinity requirements: (a) the carbon skeleton must conserve that of glutathione since analogue 14a showed the best affinity (IC50 = 5.2 microM); (b) the GST G site is not able to accommodate a chain length elongation of one methylene group (no affinity for analogues 14c,f); (c) a one-methylene group chain length reduction is tolerated, much more for the "Glu side" (14d, IC50 = 10.1 microM) than for the "Gly side" (14b, IC50 = 1800 microM); (d) the mercaptomethyl group must remain at position 5 as shown from the null affinity of the 6-mercaptomethyl analogue 14e; (e) the additional peptide isosteric E double bond (25) or hydroxyl derivative (23) in 14e did not help to retrieve affinity. This work reveals useful information for the design of new selective nonpeptidic and peptidase-stable glutathione analogues.     

Experimental investigation and thermodynamic assessment of the Cu-Sn-Ti ternary system

The Cu-Sn-Ti ternary system has been studied via experiments and thermodynamic modelling. In the experimental section, the composition of the alloys was selected based on the preliminary calculations and available literature data. Metallography, scanning electron microscopy and electron probe microanalysis were employed to analyse alloy samples prepared by arc-melting after annealing at 800 °C for 760 h. Solid phase relations at 800 °C were established. In contrast to earlier reports, the CuSn₃Ti₅ phase was interpreted as a binary intermetallic compound (Sn₃Ti₅) with extended Cu solubility. In the modelling section, three binary sub-systems were critically evaluated and updated according to the new experimental data and theoretical calculations reported in literature. According to their crystal structures and homogeneity ranges, appropriate sublattice models were proposed for SnTi₃,SnTi₂,Sn₃Ti₅ and Sn₅Ti₆. A set of self-consistent thermodynamic parameters for the Cu-Sn-Ti ternary system was obtained by considering the present experimental results and reported experimental information. The calculated results compare with the available experimental data to validate the present thermodynamic assessment.