Limitations to the Use of Woven Roving Glass Fibers in Plastic Composites,or the Case Against Woven Roving

Composite materials consist of at least two chemically distinct phases basically having a reinforcing material supported in a matrix material with a distinct reinforcement/matrix (R/M) interface separating the components; the components must be combined three-dimensionally. The composite has properties distinctly different from the properties of any constituents, which generally would not be achieved in any of the constituents acting alone. The principle is to use the plastic flow in the matrix to load the reinforcement in the direction of the applied load. To do this it is necessary to transfer and share the externally applied service loads of the composite through the weak matrix to the stronger reinforcement by a shear loading action. The job of the matrix is to transmit and distribute the stresses onto the individual fibers and to maintain the separation and orientation of the fibers. The interface is the critical factor that determines to what extent the potential properties of the composite will be achieved and maintained during usage. The interface must have the appropriate chemical and physical features in order to provide the necessary load transfer from the matrix to the reinforcement [1]. While the strain at the point of service loading is not uniformly distributed over the composite cross section, a finite distance away it does assume a uniform distribution. At this area the shear stress at the component interfaces is zero in the direction of the applied load [2].     

Minor Role of Mitochondrial Respiration for Fatty-Acid Induced Insulin Secretion

An appropriate insulin secretion by pancreatic beta-cells is necessary to maintain glucose homeostasis. A rise in plasma glucose leads to increased metabolism and an elevated cytoplasmic ATP/ADP ratio that finally triggers insulin granule exocytosis. In addition to this triggering pathway, one or more amplifying pathways—activated by amino acids or fatty acid—enhance secretion by promoting insulin granule recruitment to, and priming at, the plasma membrane. The aim of this study was to clarify the impact of the mitochondrial respiratory activity on fatty acid-induced insulin secretion that was assessed by an extracellular flux analyzer. Treatment of isolated mouse islets with glucose (20 mM) increased insulin secretion 18-fold and correlated with ATP-synthesizing respiration. Furthermore, oxygen consumption rate (OCR) significantly increased by 62% in response to glucose, whereas the addition of palmitate resulted only in a minor increase of OCR at both 2.8 mM (11%) and 20 mM glucose (21%). The addition of palmitate showed a pronounced increase of coupling efficiency (CE) at 2.8 mM glucose but no further insulin secretion. However, treatment with palmitate at 20 mM glucose increased insulin secretion about 32-fold accompanied by a small increase in CE. Thus, fatty acid induced respiration has a minor impact on insulin secretion. Our data clearly demonstrate that fatty acids in contrast to glucose play a minor role for respiration-mediated insulin secretion. In the presence of high glucose, fatty acids contribute partially to amplifying pathways of insulin secretion by further increasing mitochondrial activity in the islets of Langerhans.     

Dendrimers or Nanoparticles as Supports for the Design of Efficient and Recoverable Organocatalysts?

The Jørgensen–Hayashi catalyst [(S)‐α,α‐diphenylprolinol trimethylsilyl ether] was grafted onto the surface of two different supports: phosphorus dendrimers (generations 1 to 3) and magnetic, polymer‐coated cobalt/carbon (Co/C) nanobeads. These new supported catalysts displayed high activities and selectivities in the Michael additions of a wide range of aldehydes to different nitroolefins. Moreover, the dendrimer of the third generation displayed excellent recycling abilities since it could be recovered and reused in 7 consecutive runs without loss of activity.     

New inhibitors of the Tat-TAR RNA interaction found with a "fuzzy" pharmacophore model

TAR RNA is a potential target for AIDS therapy. Ligand-based virtual screening was performed to retrieve novel scaffolds for RNA-binding molecules capable of inhibiting the Tat-TAR interaction, which is essential for HIV replication. We used a "fuzzy" pharmacophore approach (SQUID) and an alignment-free pharmacophore method (CATS3D) to carry out virtual screening of a vendor database of small molecules and to perform "scaffold-hopping". A small subset of 19 candidate molecules were experimentally tested for TAR RNA binding in a fluorescence resonance energy transfer (FRET) assay. Both methods retrieved molecules that exhibited activities comparable to those of the reference molecules acetylpromazine and chlorpromazine, with the best molecule showing ten times better binding behavior (IC50 = 46 microM). The hits had molecular scaffolds different from those of the reference molecules.     

Are hormones from the neuropeptide Y family recognized by their receptors from the membrane-bound state?

Hormones and many other neurotransmitters, growth factors, odorant molecules, and light all present stimuli for a class of membrane-anchored receptors called G protein-coupled receptors (GPCRs). The GPCRs are the largest family of cell-surface receptors involved in signal transduction. About 1% of all known genes of Drosophila and more than 5% of the genes of Caenorhabditis elegans encode GPCRs. In addition, more than 50% of current therapeutic agents on the market target these receptors. When the enormous biological and pharmaceutical importance of these receptors is considered, it is surprising how little is known about the mechanism with which these receptors recognize their natural ligands. In this review we present a structural approach, utilizing techniques of high-resolution NMR spectroscopy, to address the question of whether peptides from the neuropeptide Y family of neurohormones are recognized directly from solution or from the membrane-bound state. In our studies we discovered that the structures of the membrane-bound species are better correlated to the pharmacological properties of these peptides than the solution structures are. These findings are supported by the observation that many biophysical properties of these peptides seem to be optimized for membrane binding. We finally present a scenario of possible events during receptor recognition.     

Comparison of Olefin Polymerization Processes with Metallocene Catalysts

Summary: Solution and gas phase processes of the polymerization of ethene are compared using new types of pentalenyl bridged ansa‐metallocenes such as [Me₃Pen(Flu)]ZrCl₂. As of the bridge, the catalyst system is remarkable thermostable up to 105 °C and a deactivation of the metallocene on the silica support can be suppressed. Compared to the non‐supported catalyst in a solution process, the application of the heterogenized system in a gas phase process leads to a decrease in activities while molar masses of the polyethenes are similar. Due to a higher degree of short chain branches of 20–30 per 1 000 carbon atoms instead of 10–17, the melting temperatures are 10 °C lower than those for polymers obtained in the solution process.

Basic structure of the here used pentalenyl bridged ansa‐metallocenes.     

NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases

Nerve growth factor (NGF) is known to intensify pain in various ways, so perturbing pertinent effects without negating its essential influences on neuronal functions could help the search for much-needed analgesics. Towards this goal, cultured neurons from neonatal rat trigeminal ganglia—a locus for craniofacial sensory nerves—were used to examine how NGF affects the Ca²⁺-dependent release of a pain mediator, calcitonin gene-related peptide (CGRP), that is triggered by activating a key signal transducer, transient receptor potential vanilloid 1 (TRPV1) with capsaicin (CAP). Measurements utilised neurons fed with or deprived of NGF for 2 days. Acute re-introduction of NGF induced Ca²⁺-dependent CGRP exocytosis that was inhibited by botulinum neurotoxin type A (BoNT/A) or a chimera of/E and/A (/EA), which truncated SNAP-25 (synaptosomal-associated protein with Mr = 25 k) at distinct sites. NGF additionally caused a Ca²⁺-independent enhancement of the neuropeptide release evoked by low concentrations (<100 nM) of CAP, but only marginally increased the peak response to ≥100 nM. Notably, BoNT/A inhibited CGRP exocytosis evoked by low but not high CAP concentrations, whereas/EA effectively reduced responses up to 1 µM CAP and inhibited to a greater extent its enhancement by NGF. In addition to establishing that sensitisation of sensory neurons to CAP by NGF is dependent on SNARE-mediated membrane fusion, insights were gleaned into the differential ability of two regions in the C-terminus of SNAP-25 (181–197 and 198–206) to support CAP-evoked Ca²⁺-dependent exocytosis at different intensities of stimulation.     

Orthogonal Peptide-Templated Labeling Elucidates Lateral ETAR/ETBR Proximity and Reveals Altered Downstream Signaling

Fine-tuning of G protein-coupled receptor (GPCR) signaling is important to maintain cellular homeostasis. Recent studies demonstrated that lateral GPCR interactions in the cell membrane can impact signaling profiles. Here, we report on a one-step labeling method of multiple membrane-embedded GPCRs. Based on short peptide tags, complementary probes transfer the cargo (e. g. a fluorescent dye) by an acyl transfer reaction with high spatial and temporal resolution within 5 min. We applied this approach to four receptors of the cardiovascular system: the endothelin receptor A and B (ET_AR and ET_BR), angiotensin II receptor type 1, and apelin. Wild type-like G protein activation after N-terminal modification was demonstrated for all receptor species. Using FRET-competent dyes, a constitutive proximity between hetero-receptors was limited to ET_AR/ET_BR. Further, we demonstrate, that ET_AR expression regulates the signaling of co-expressed ET_BR. Our orthogonal peptide-templated labeling of different GPCRs provides novel insight into the regulation of GPCR signaling.