Structure–Activity Relationship Study of Spider Polyamine Toxins as Inhibitors of Ionotropic Glutamate Receptors

The spider polyamine toxins Joro spider toxin‐3 (JSTX‐3) and Nephila polyamine toxins‐1 and ‐8 (NPTX‐1 and NPTX‐8) are isolated from the venom of the orb‐weaver spider Nephila clavata (Joro spider). They share a high degree of structural resemblance, their aromatic head groups being the only difference, and were recently found to be very potent open‐channel blockers of ionotropic glutamate (iGlu) receptors. In this study we designed and synthesized a collection of 24 analogues of these toxins using a recently developed solid‐phase synthetic methodology. Systematic variation in two regions of the toxins and subsequent evaluation of biological activity at AMPA and NMDA subtypes of iGlu receptors provided succinct information on structure–activity relationships. In particular, one set of analogues were found to display exquisite selectivity and potency for AMPA receptors relative to the natural products. Thus, this systematic SAR study has provided new pharmacological tools for studies of iGlu receptors.     

Interface structure and strength of ultrasonically wedge bonded heavy aluminium wires in Si-based power modules

In this paper the microscopical structure of wedge bonded interfaces is investigated, with a focus on what effect the power in the ultrasonic bonding and the initial microscopical structure of the \(Al\) wire have on the quality of the bonding. The quality evaluation is based on mapping the microscopical restructuring of the wire grains during bonding and thereby assessing the effective bonding area. Three approaches are utilized in the interface characterization: mechanical shear test, optical microscopy combined with micro-sectioning, and scanning electron microscopy assisted by focused ion beam milling. The shear test is applied to quantify the strength of the bonded interfaces, while the other methods are used to map the grain reconstruction caused by the bonding. From the results it is possible to map a 3D image of the wire deformation, and the grain refinement region which is the dominating parameter with respect to fatigue related cracking of the interfaces. It is found that the bonding power, as well as the initial wire structure directly affects the refinement region and thereby the strength of the interface.     

Stabilization of plutonium nano-colloids by epitaxial distortion on mineral surfaces

The subsurface migration of Pu may be enhanced by the presence of colloidal forms of Pu. Therefore, complete evaluation of the risk posed by subsurface Pu contamination needs to include a detailed physical/chemical understanding of Pu colloid formation and interactions of Pu colloids with environmentally relevant solid phases. Transmission electron microscopy (TEM) was used to characterize Pu nanocolloids and interactions of Pu nanocolloids with goethite and quartz. We report that intrinsic Pu nanocolloids generated in the absence of goethite or quartz were 2-5 nm in diameter, and both electron diffraction analysis and HRTEM confirm the expected Fm3m space group with the fcc, PuO2 structure. Plutonium nanocolloids formed on goethite have undergone a lattice distortion relative to the ideal fluorite-type structure, fcc, PuO2, resulting in the formation of a bcc, Pu4O7 structure. This structural distortion results from an epitaxial growth of the plutonium colloid on goethite, leading to stronger binding of plutonium to goethite compared with other minerals such as quartz, where the distortion was not observed. This finding provides new insight for understanding how molecular-scale behavior at the mineral-water interface may facilitate transport of plutonium at the field scale.     

Monolithic ZnTe-based pillar microcavities containing CdTe quantum dots

Micropillars of different diameters have been prepared by focused ion beam milling out of a planar ZnTe-based cavity. The monolithic epitaxial structure, deposited on a GaAs substrate, contains CdTe quantum dots embedded in a ZnTe λ-cavity delimited by two distributed Bragg reflectors (DBRs). The high refractive index material of the DBR structure is ZnTe, while for the low index material a short-period triple MgTe/ZnTe/MgSe superlattice is used. The CdTe quantum dots are formed by a novel Zn-induced formation process and are investigated by scanning transmission electron microscopy. Micro-photoluminescence measurements show discrete optical modes for the pillars, in good agreement with calculations based on a vectorial transfer matrix method. The measured quality factor reaches a value of 3100.     

Reconfiguration of spectral absorption features using a frequency-chirped laser pulse

A technique is proposed to manipulate atomic population in an inhomogeneously broadened medium, which can set an arbitrary absorption spectrum to a uniform transparency (erasure) or to a nearly complete inversion. These reconfigurations of atomic spectral distribution are achieved through excitation of electronic transitions using a laser pulse with chirped frequency, which precisely affects selected spectral regions while leaving the rest of the spectrum unperturbed. An erasure operation sets the final atomic population inversion to zero and the inversion operation flips the population between the ground and the excited states, regardless of the previously existing population distribution. This technique finds important applications both in optical signal processing, where fast, recursive processing and high dynamic range are desirable and in quantum memory and quantum computing, which both require high efficiency and high fidelity in quantum state preparation of atomic ensembles. Proof-of-concept demonstrations were performed in a rare-earth doped crystal.     

Gravity drainage of activated sludge: new experimental method and considerations of settling velocity, specific cake resistance and cake compressibility

A laboratory scale setup was used for characterization of gravitational drainage of waste activated sludge. The aim of the study was to assess how time of drainage and cake dry matter depended on volumetric load, SS content and sludge floc properties. It was demonstrated that activated sludge forms compressible cakes, even at the low pressures found in gravitational drainage. The values of specific cake resistance were two to three orders of magnitude lower than those obtained in pressure filtration. Despite the compressible nature of sludge, key macroscopic parameters such as time of drainage and cake solid content showed simple functional dependency of the volumetric load and SS of a given sludge. This suggests that the proposed method may be applied for design purposes without the use of extensive numerical modeling. The possibilities for application of this new technique are, among others, the estimation of sludge drainability prior to mechanical dewatering on a belt filter, or the application of surplus sludge on reed beds, as well as adjustments of sludge loading, concentration or sludge pre-treatment in order to optimize the drainage process.     

Intracellularly Degradable Hydrogen‐Bonded Polymer Capsules

The assembly of low‐fouling polymer capsules with redox‐responsive behavior and intracellular degradability is reported. Thiol‐containing poly(2‐ethyl‐2‐oxazoline) (PEtOxMA_SH) brushes are synthesized by atom transfer radical polymerization (ATRP) of oligo(2‐ethyl‐2‐oxazoline)methacrylate and glycidyl methacrylate (GMA) and subsequent ring‐opening reaction of the GMA. Sequential deposition of PEtOxMA_SH/poly(methacrylic acid) (PMA) multilayers onto silica (SiO₂) particle templates and crosslinking through disulfide formation yield stable capsules after the removal of the SiO₂ templates by buffered hydrofluoric acid (HF). The redox‐responsive nature of the disulfide crosslinking groups enables the degradation of these capsules under simulated intracellular conditions at pH 5.9 and 5 mm glutathione (GSH). Furthermore, capsule degradation is observed after incubation with dendritic (JAWS II) cells. Even at high capsule‐to‐cell ratios, PEtOxMA_SH capsules show only negligible cytotoxicity. Quartz crystal microgravimetry (QCM) studies, using 100% human serum, reveal that films prepared from PEtOxMA_SH exhibit low‐fouling properties. The degradation and low‐fouling properties are promising for application of PEtOxMA_SH films/capsules for the delivery and triggered release of therapeutics.     

Two Subgroups within the GH43_36 α-l-Arabinofuranosidase Subfamily Hydrolyze Arabinosyl from Either Mono-or Disubstituted Xylosyl Units in Wheat Arabinoxylan

Fungal arabinofuranosidases (ABFs) catalyze the hydrolysis of arabinosyl substituents (Ara) and are key in the interplay with other glycosyl hydrolases to saccharify arabinoxylans (AXs). Most characterized ABFs belong to GH51 and GH62 and are known to hydrolyze the linkage of α-(1→2)-Ara and α-(1→3)-Ara in monosubstituted xylosyl residues (Xyl) (ABF-m2,3). Nevertheless, in AX a substantial number of Xyls have two Aras (i.e., disubstituted), which are unaffected by ABFs from GH51 and GH62. To date, only two fungal enzymes have been identified (in GH43_36) that specifically release the α-(1→3)-Ara from disubstituted Xyls (ABF-d3). In our research, phylogenetic analysis of available GH43_36 sequences revealed two major clades (GH43_36a and GH43_36b) with an expected substrate specificity difference. The characterized fungal ABF-d3 enzymes aligned with GH43_36a, including the GH43_36 from Humicola insolens (HiABF43_36a). Hereto, the first fungal GH43_36b (from Talaromyces pinophilus) was cloned, purified, and characterized (TpABF43_36b). Surprisingly, TpABF43_36b was found to be active as ABF-m2,3, albeit with a relatively low rate compared to other ABFs tested, and showed minor xylanase activity. Novel specificities were also discovered for the HiABF43_36a, as it also released α-(1→2)-Ara from a disubstitution on the non-reducing end of an arabinoxylooligosaccharide (AXOS), and it was active to a lesser extent as an ABF-m2,3 towards AXOS when the Ara was on the second xylosyl from the non-reducing end. In essence, this work adds new insights into the biorefinery of agricultural residues.     

Bioinformatics Analysis of RNA-seq Data Reveals Genes Related to Cancer Stem Cells in Colorectal Cancerogenesis

Cancer stem cells (CSC) play one of the crucial roles in the pathogenesis of various cancers, including colorectal cancer (CRC). Although great efforts have been made regarding our understanding of the cancerogenesis of CRC, CSC involvement in CRC development is still poorly understood. Using bioinformatics and RNA-seq data of normal mucosa, colorectal adenoma, and carcinoma (n = 106) from GEO and TCGA, we identified candidate CSC genes and analyzed pathway enrichment analysis (PEI) and protein–protein interaction analysis (PPI). Identified CSC-related genes were validated using qPCR and tissue samples from 47 patients with adenoma, adenoma with early carcinoma, and carcinoma without and with lymph node metastasis and were compared to normal mucosa. Six CSC-related genes were identified: ANLN, CDK1, ECT2, PDGFD, TNC, and TNXB. ANLN, CDK1, ECT2, and TNC were differentially expressed between adenoma and adenoma with early carcinoma. TNC was differentially expressed in CRC without lymph node metastases whereas ANLN, CDK1, and PDGFD were differentially expressed in CRC with lymph node metastases compared to normal mucosa. ANLN and PDGFD were differentially expressed between carcinoma without and with lymph node metastasis. Our study identified and validated CSC-related genes that might be involved in early stages of CRC development (ANLN, CDK1, ECT2, TNC) and in development of metastasis (ANLN, PDGFD).     

Physico-chemical characteristics of full scale sewage sludges with implications to dewatering

An investigation was carried out for a variety of different sewage sludges in order to establish correlations between sludge composition, structure and dewatering properties. Results indicated that the fraction of extracellular polymeric substances (EPS) in sludges was the most important parameter with respect to sludge structure. With high EPS contents, sludges had a lower shear sensitivity and lower degree of dispersion. This in turn lead to better filterability in terms of low resistance to filtration (SRF). The floc stabilising role of EPS components was not consistent with DLVO-theory, as the zeta-potential increased with increased EPS content due to increased EPS charge content. This indicates that polymer entanglement is a key factor to stable floc structure. This does not rule out the possible change in dispersion due to changed electrostatic repulsion for a given EPS content. While EPS had a good effect on floc stability and filterability, the cake dry matter content decreased with large EPS contents. This could be due to an osmotic pressure related to the polymer charge quantity, or it could be caused by water entrapment in the floc structures. A high degree of sludge dispersion increased the cake dry matter content in filtration. This mechanism is, however, impractical due to high SRF and not important to conditioned sludge. In practice, dewatering also includes sludge expression. Taking this into account, osmosis related to EPS charges is likely to be increasingly important (increasing the negative effect of EPS content on cake dry matter).