Polylactide‐block‐Polypeptide‐block‐Polylactide Copolymer Nanoparticles with Tunable Cleavage and Controlled Drug Release

A versatile nanoparticle system is presented in which drug release is triggered by enzymatic polymer cleavage, resulting in a physicochemical change of the carrier. The polylactide‐block‐peptide‐block‐polylactide triblock copolymer is generated by initiation of the ring‐opening polymerization of L‐lactide with a complex bifunctional peptide having an enzymatic recognition and cleavage site (Pro‐Leu‐Gly‐Leu‐Ala‐Gly). This triblock copolymer is specifically bisected by matrix metalloproteinase‐2 (MMP‐2), an enzyme overexpressed in tumor tissues. Triblock copolymer nanoparticles formed by nonaqueous emulsion polymerization are readily transferred into aqueous media without aggregation, even in the presence of blood serum. Cleavage of the triblock copolymer leads to a significant decrease of the glass transition temperature (T_g) from 39 °C to 31 °C, likely mediating cargo release under physiological conditions. Selective drug targeting is demonstrated by hampered mitosis and increased cell death resulting from drug release via MMP‐2 specific cleavage of triblock copolymer carrier. On the contrary, nanocarriers having a scrambled (non‐recognizable) peptide sequence do not cause enhanced cytotoxicity, demonstrating the enzyme‐specific cleavage and subsequent drug release. The unique physicochemical properties, cleavage‐dependent cargo release, and tunability of carrier bioactivity by simple peptide exchange highlight the potential of this polymer‐nanoparticle concept as platform for custom‐designed carrier systems.     

Energy dissipation in laser-based free form heading: a numerical approach

Cold forming generally allows the fast generation of parts with very low tolerances. In addition, mechanical properties are improved, if work hardening materials are used. Transferring the cold forming process to micro range leads to a decrease in the maximum achievable upset ratio so that the forming process becomes inefficient. Therefore, a laser-based free form heading process has been developed to generate preforms which can be calibrated in a secondary cold forming step. The achievable upset ratios reach values of several hundreds instead of 2.1 which is common for single step mechanical upsetting. In this article, heat losses arising in the material accumulation process using laser-based free form heading are analyzed and discussed. For this purpose, the process is modeled within the framework of continuum mechanics and simulated by a finite element method. By using a numerical approach, a systematic study on heat losses is performed in order to identify the influence of radiation, heat transfer due to convection and thermal conduction during laser irradiation time. The simulation results, which are validated with experimental data, show that the radiation is the most important mechanism reducing the efficiency of the accumulation process.     

Hyperthermostabilization of Bacillus licheniformis{alpha}-amylase and modulation of its stability over a 50{degrees}C temperature range

Bacillus licheniformis     

Iraqi-Jewish kindreds with optic atrophy plus (3-methylglutaconic aciduria type 3) demonstrate linkage disequilibrium with the CTG repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene

Iraqi-Jewish optic atrophy plus is an autosomal recessive condition characterized by infantile optic atrophy, an early onset movement disorder, and 3-methylglutaconic aciduria. Other features include spastic paraplegia, mild ataxia, mild cognitive deficiency and dysarthria. This disorder was identified in inbred Iraqi-Jewish kindreds in which relationships between most of the affected individuals were unknown. In this study we identify linkage to chromosome 19q13.2-q13.3 by using a DNA pooling strategy to perform a genome wide screen followed by a high density search for shared segments among affected individuals in candidate regions identified in the initial genome wide screen. A significantly high positive lod score of 6.14 at zero recombination was obtained for the CTG repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene. The existence of multiple recombinant individuals indicates the disease interval can be further narrowed with additional markers. Linkage disequilibrium was seen in six polymorphic markers across a 1 Mb interval. This region is well characterized and contains several candidate genes.     

Short time creep behaviour of Invar steel

During processing of so‐called true flat shadow/masks made of Invar steel for large size TV screens the mask is stretched onto a solid frame. Mask and frame are submitted to a final heat treatment (blackening treatment) in order to enhance the emissivity of the material. Elevated temperatures and pretension makes the mask material prone to plastic straining, resulting in disutility of the unit for the application. From a technological point of view, the material behaviour under these conditions has been defined as short time creep behaviour. The mechanisms causing creep in this special case are not fully understood. Focus of the present work was the examination of the effect of cube twins on the short time creep behaviour of the investigated Invar steel by texture analysis using EBSD technology. This investigation was conducted under four different material conditions covering a whole set of production steps during shadowmask processing. Detailed information about the change of the volume fractions and the orientation of characteristic texture components, most of all the cube twins, could be gained. The observations revealed that during the creep test two types of cube twins make an orientation change, thus plastic deformation takes place, causing relaxation of the material. The observation of cube twin rotation during the creep test is partly confirmed by the simulation of the respective Taylor factors.     

Energy Scales in the High-T c Superconductor YBa2Cu3O6+x

The optical conductivity sum rule is used to examine the evolution of the spectral weight N(ω) in both the normal and superconducting states of optimally and underdoped YBa₂Cu₃O_6+x along the a axis. Differences in N(ω) above and below T _c allow the strength of the superconducting condensate ρ_s to be determined. In the optimally-doped material, ρ_s is fully formed at energies comparable to the full superconducting gap maximum (?0.1 eV), while in the underdoped material the energy scale for convergence is considerably higher (?0.6 eV). This difference is discussed in terms of normal-state properties.     

Top-Seeded Melt-Growth of YBa2Cus3Ox Crystals for Neutron Diffraction Studies

We have grown cubic centimeter-size crystals of YBa₂Cu₃O _x suitable for neutron studies, by a top-seeded melt-growth technique. Growth conditions were optimized with an eye toward maximizing phase purity. It was found that the addition of 2% Y₂BaCuO₅ and 0.5% Pt (by mass) were required to prevent melt loss and to obtain the highest crystallinity. A neutron diffraction study on a mosaic of six such crystals found that the final Y₂BaCuO₅ concentration was 5%, while other impurity phases comprised less than 1% by volume. The oxygen content was set to x = 6.5, the crystals were detwinned, and then carefully annealed to give the well-ordered ortho-II phase. The neutron study determined that 70% of the mosaic's volume was in the majority orthorhomic domain. The neutron (006) and (110) rocking curve widths were ～1° per crystal and ～2.2° for the mosaic, and the oxygen chain correlation lengths were >100 Å in the a- and b-directions and ～50 Å in the c-direction.     

Nanostructured diamond-like carbon on digital versatile disc as a matrix-free target for laser desorption/ionization mass spectrometry

A nanostructured diamond-like carbon (DLC) coated digital versatile disk (DVD) target is presented as a matrix-free sample support for application in laser desorption/ionization mass spectrometry (LDI-MS). A large number of vacancies, defects, relative sp(2) carbon content, and nanogrooves of DLC films support the LDI phenomenon. The observed absorptivity of DLC is in the range of 305-330 nm (nitrogen laser, 337 nm). The universal applicability is demonstrated through different analytes like amino acids, carbohydrates, lipids, peptides, and other metabolites. Carbohydrates and amino acids are analyzed as sodium and potassium adducts. Peptides are detectable in their protonated forms, which avoid the extra need of additives for ionization. A bovine serum albumin (BSA) digest is analyzed to demonstrate the performance for peptide mixtures, coupled with the material-enhanced laser desorption/ionization (MELDI) approach. The detection limit of the described matrix-free target is investigated to be 10 fmol/microL for [Glu(1)]-fibrinopeptide B (m/z 1570.6) and 1 fmol/microL for L-sorbose (Na(+) adduct). The device does not require any chemical functionalization in contrast to other matrix-free systems. The inertness of DLC provides longer lifetimes without any deterioration in the detection sensitivity. Broad applicability allows high performance analysis in metabolomics and peptidomics. Furthermore the DLC coated DVD (1.4 GB) sample support is used as a storage device for measured and processed data together with sampling on a single device.     

Anomalous independence of multiple exciton generation on different group IV-VI quantum dot architectures

Multiple exciton generation (MEG) in PbSe quantum dots (QDs), PbSe(x)S(1-x) alloy QDs, PbSe/PbS core/shell QDs, and PbSe/PbSe(y)S(1-y) core/alloy-shell QDs was studied with time-resolved optical pump and probe spectroscopy. The optical absorption exhibits a red-shift upon the introduction of a shell around a PbSe core, which increases with the thickness of the shell. According to electronic structure calculations this can be attributed to charge delocalization into the shell. Remarkably, the measured quantum yield of MEG, the hot exciton cooling rate, and the Auger recombination rate of biexcitons are similar for pure PbSe QDs and core/shell QDs with the same core size and varying shell thickness. The higher density of states in the alloy and core/shell QDs provide a faster exciton cooling channel that likely competes with the fast MEG process due to a higher biexciton density of states. Calculations reveal only a minor asymmetric delocalization of holes and electrons over the entire core/shell volume, which may partially explain why the Auger recombination rate does not depend on the presence of a shell.