Display Selection of a Hybrid Foldamer-Peptide Macrocycle.

Expanding the chemical diversity of peptide macrocycle libraries for display selection is desirable to improve their potential to bind biomolecular targets. We now have implemented a considerable expansion through a large aromatic helical foldamer inclusion. A foldamer was first identified that undergoes flexizyme-mediated tRNA acylation and that is capable of initiating ribosomal translation with yields sufficiently high to perform an mRNA display selection of macrocyclic foldamer-peptide hybrids.

Investigations on the Nonlinear Optical Properties of 0D, 1D, and 2D Boron Nitride Nanomaterials in the Visible Spectral Region.

In recent years, boron nitride nanomaterials have attracted increasing attention due to their unique properties such as high temperature stability and high thermal conductivity. They are structurally analogous to carbon nanomaterials and can also be generated as zero-dimensional nanoparticles and fullerenes, one-dimensional nanotubes and nanoribbons, and two-dimensional nanosheets or platelets. In contrast to carbon-based nanomaterials, which have been extensively studied during recent years, the optical limiting properties of boron nitride nanomaterials have hardly been analysed so far.

Differential Peptide Multi-Macrocyclizations at the Surface of a Helical Foldamer Template.

Hybrid sequences comprising a peptide with several Cys residues and an aromatic foldamer helix with several chloroacetamide functions at its surface were synthesized. Such products may in principle form numerous macromulticyclic thioether products by intramolecularly combining all Cys residues and all chloroacetamide functions. However, we show that the reactive sites on the structurally defined helix can be placed at such locations that the peptide selectively stitches itself to form a series of different macrocycles within mostly one preferred product.

How big is the little brain in the gut? Neuronal numbers in the enteric nervous system of mice, Guinea pig, and human.

Background: Despite numerous studies on the enteric nervous system (ENS), we lack fundamental knowledge on neuronal densities or total neuron numbers in different species. There are more anecdotal than actual figures on nerve counts.

Methods: We used standardized preparation techniques and immunohistochemistry with validated panneuronal markers (human or mouse anti-HuD/C) to determine neuronal densities in specimen from the entire gastrointestinal tract of mice, guinea pig, and humans.

Service Robots for Context Recognition in Smart Environments.

Background: A new concept for context recognition involves a smart home system, wearables, and service robots.

Objectives: To find the best suited robot platform for the given use case.

Methods: An assessment of available service robots based on various factors is carried out.

Absolute spectral backscatter measurements of large-core multimode PMMA polymer optical fibers.

To our knowledge, we are the first to measure the absolute value of the backscattering coefficient of a standard 1 mm core-diameter, multimode (MM) step-index (SI) polymethylmethacrylate (PMMA) polymer optical fiber (POF) for the spectral range of 450 nm to 700 nm. Our optical time domain reflectometer (OTDR) setup consists of a femtosecond supercontinuum laser with an acousto-optical filter as a tunable light source with short pulses and a time-correlated single-photon counting system as a receiver with a high dynamic range. The backscattering coefficient is calculated from the ratio between the energy within the fiber end reflex and the distributed backscattering level.

Conformational interplay in hybrid peptide-helical aromatic foldamer macrocycles.

Macrocyclic peptides are an important class of bioactive substances. When inserting an aromatic foldamer segment in a macrocyclic peptide, the strong folding propensity of the former may influence the conformation and alter the properties of the latter. Such an insertion is relevant because some foldamer-peptide hybrids have recently been shown to be tolerated by the ribosome, prior to forming macrocycles, and can thus be produced using an translation system.

Extended surgical safety margins and ulceration are associated with an improved prognosis in pleomorphic dermal sarcomas.

Background: Pleomorphic dermal sarcomas (PDS) are frequent UV-induced sarcomas of the skin of intermediate grade malignant potential. Despite the fact that PDS have a noteworthy potential to recur (up to 28%) as well as to metastasize (up to 20%), there are no specific clinical guidelines with respect to follow-up these patients. Moreover, little is known about clinical, histological or molecular prognostic factors in PDS.

A new ALK isoform transported by extracellular vesicles confers drug resistance to melanoma cells.

Background: Drug resistance remains an unsolved clinical issue in oncology. Despite promising initial responses obtained with BRAF and MEK kinase inhibitors, resistance to treatment develops within months in virtually all melanoma patients.

Methods: Microarray analyses were performed in BRAF inhibitor-sensitive and resistant cell lines to identify changes in the transcriptome that might play a role in resistance.

Precise Enzymatic Cleavage Sites for Improved Bioactivity of siRNA Lipo-Polyplexes.

Sequence-defined cationic lipo-oligomers are potent siRNA carriers, forming stable lipo-polyplexes based on both electrostatic and hydrophobic interactions and, after endocytosis and endosomal protonation, facilitating the delivery of siRNA into the cytosol. After completion of the nucleic acid delivery process, carriers should be readily biodegradable to ensure minimum accumulation of amphiphilic molecules that are harmful to lysosomes and other intracellular organelles. Endolysosomal enzymes may degrade a surplus of carrier molecules left over in lysosomes and thereby facilitate the generation and rapid excretion of cleavage products.

[Acute emergencies in oncology].

The spectrum of dermato-oncological emergencies is multifaceted. They are particularly observed in cases with malignant melanoma due to the large number of patients and prolonged survival rates that are associated with new therapies for advanced disease. Dermato-oncological patients present to the hospital with symptoms like nausea and emesis, unexpected neurological deficits, various gastrointestinal problems, and even acute abdomen, acute breathlessness, or hemoptysis.

Brightfield proximity ligation assay reveals both canonical and mixed transforming growth factor-β/bone morphogenetic protein Smad signaling complexes in tissue sections.

Transforming growth factor-β (TGF-β) is an important regulator of cellular homeostasis and disease pathogenesis. Canonical TGF-β signaling occurs through Smad2/3-Smad4 complexes; however, recent in vitro studies suggest that elevated levels of TGF-β may activate a novel mixed Smad complex (Smad2/3-Smad1/5/9), which is required for some of the pro-oncogenic activities of TGF-β. To determine if mixed Smad complexes are evident in vivo, we developed antibodies that can be used with a proximity ligation assay to detect either canonical or mixed Smad complexes in formalin-fixed paraffin-embedded sections.

How specific are ion specificities? A pilot NMR study.

NMR quadruple splitting measurements are a useful technique to investigate the adsorption behaviour of ions near to charged surfaces in liquid crystals made of surfactants of different headgroups. In the present paper we show the differences in lithium and sodium adsorption on dodecyl carboxylate and dodecyl sulphate bilayers as a function of surfactant concentration and for two temperatures. To this purpose we mixed the pure surfactants and also mixtures of the lithium and sodium surfactants with octanol as a cosurfactant in appropriate ratios and concentrations to obtain liquid crystals.

Size and shape effects on the nonlinear optical behavior of silver nanoparticles for power limiters.

The optical limiting behavior of silver nanoparticles with different sizes and shapes is investigated and compared to the optical limiting performance of conventional carbon black suspension (CBS). The optical limiting behavior is characterized by means of nonlinear transmittance and scattered intensity measurements when submitted to nanosecond pulsed Nd:YAG lasers operating at the fundamental or the second harmonic wavelength. We found that the optical limiting effect is strongly particle size dependent and the best performance is achieved with the smaller particles.

Spontaneous skin erosions and reduced skin and corneal wound healing characterize CLIC4(NULL) mice.

Cutaneous wound healing is a complex process involving blood clotting, inflammation, migration of keratinocytes, angiogenesis, and, ultimately, tissue remodeling and wound closure. Many of these processes involve transforming growth factor-β (TGF-β) signaling, and mice lacking components of the TGF-β signaling pathway are defective in wound healing. We show herein that CLIC4, an integral component of the TGF-β pathway, is highly up-regulated in skin wounds.

Group therapy with the antisocial spinal-cord-injured patient.

This conceptual article attempts to help health care professionals deepen their understanding of the psychological characteristics of antisocial spinal cord-injured patients that predispose them to injury, being a disruptive influence on the medical floor, oppositional acting out with physicians, and potentially thwarting effective treatment. Group techniques are described that appear to improve the adaptation of these patients to their traumatic injury and hospital environment.