Spatial Structure of the Branching Streamer Channels in a Corona Discharge

The dendritic structure of streamer channels in a corona discharge is described by using fractal theory. It is found that, for a needle-plane discharge, the fractal dimension of the plasma structure is D = 2.16 ± 0.05. The computed spatial distributions of the branching ratios are compared with the available experimental data. The influence of the branching processes on the distribution of chemically active radicals in streamer corona discharges is studied.     

Yohimbine as a Starting Point to Access Diverse Natural Product-Like Agents with Re-programmed Activities against Cancer-Relevant GPCR Targets

G protein-coupled receptors (GPCRs) constitute the largest protein superfamily in the human genome. GPCRs play key roles in mediating a wide variety of physiological events including proliferation and cancer metastasis. Given the major roles that GPCRs play in mediating cancer growth, they present promising targets for small molecule therapeutics. One of the principal goals of our lab is to identify complex natural products (NPs) suitable for ring distortion, or the dramatic altering of the inherently complex architectures of NPs, to rapidly generate an array of compounds with diverse molecular skeletal systems. The overarching goal of our ring distortion approach is to re-program the biological activity of select natural products and identify new compounds of importance to the treatment of disease, such as cancer. Described herein are the results from biological screens of diverse small molecules derived from the indole alkaloid yohimbine against a panel of GPCRs involved in various diseases. Several analogues displayed highly differential antagonistic activities across the GPCRs tested. We highlight the re-programmed profile of one analogue, Y7g, which exhibited selective antagonistic activities against AVPR2 (IC₅₀ = 459 nM) and OXTR (IC₅₀ = 1.16 µM). The activity profile of Y7g could correlate its HIF-dependent anti-cancer activity to its GPCR antagonism since these receptors are known to be upregulated in hypoxic cellular environments. Our findings demonstrate that the ring distortion of yohimbine can lead to the identification of new compounds capable of interacting with distinct cancer-relevant targets.     

Mechanisms of Side Branching and Tip Splitting in a Model of Branching Morphogenesis

Recent experimental work in lung morphogenesis has described an elegant pattern of branching phenomena. Two primary forms of branching have been identified: side branching and tip splitting. In our previous study of lung branching morphogenesis, we used a 4 variable partial differential equation (PDE), due to Meinhardt, as our mathematical model to describe the reaction and diffusion of morphogens creating those branched patterns. By altering key parameters in the model, we were able to reproduce all the branching styles and the switch between branching modes. Here, we attempt to explain the branching phenomena described above, as growing out of two fundamental instabilities, one in the longitudinal (growth) direction and the other in the transverse direction. We begin by decoupling the original branching process into two semi-independent sub-processes, 1) a classic activator/inhibitor system along the growing stalk, and 2) the spatial growth of the stalk. We then reduced the full branching model into an activator/inhibitor model that embeds growth of the stalk as a controllable parameter, to explore the mechanisms that determine different branching patterns. We found that, in this model, 1) side branching results from a pattern-formation instability of the activator/inhibitor subsystem in the longitudinal direction. This instability is far from equilibrium, requiring a large inhomogeneity in the initial conditions. It successively creates periodic activator peaks along the growing stalk, each of which later on migrates out and forms a side branch; 2) tip splitting is due to a Turing-style instability along the transversal direction, that creates the spatial splitting of the activator peak into 2 simultaneously-formed peaks at the growing tip, the occurrence of which requires the widening of the growing stalk. Tip splitting is abolished when transversal stalk widening is prevented; 3) when both instabilities are satisfied, tip bifurcation occurs together with side branching.     

栲树不同生长发育阶段的枝系特征分析

对浙江天童国家森林公园内常绿阔叶优势树种栲树(Castanopsis fargesii)不同发育阶段植冠内的分枝式样特征进行了统计分析。结果表明：栲树在不同发育阶段的总体分枝率和逐步分枝率有显著变化,幼苗和幼树阶段的分枝率较低,而成株阶段的分枝率较高;幼树阶段的枝条长度、枝倾角和叶倾角明显大于幼苗和成株阶段,表现为明显的高生长对策;叶片配置在不同枝系上有较大差异,叶片主要集中于植冠内一级枝和二级枝上;叶片的大小从幼苗、幼树到成株阶段逐渐增大。研究结果表明栲树在生活史的不同生长发育阶段,分枝式样表现出一定的可塑性,反映了不同的适应对策。     

Critical Evaluation of Branch Polarity and Apical Dominance as Dictators of Colony Astogeny in a Branching Coral

The high morphological resemblance between branching corals and trees, can lead to comparative studies on pattern formation traits, best exemplified in plants and in some cnidarians. Here, 81 branches of similar size of the hermatypic coral Stylophora pistillata were lopped of three different genets, their skeletons marked with alizarin red-S, and divided haphazardly into three morphometric treatment groups: (I) upright position; (II) horizontal position, intact tip; and (III) horizontal position, cut tip. After 1 y of in-situ growth, the 45 surviving ramets were brought to the laboratory, their tissues removed and their architectures analyzed by 22 morphological parameters (MPs). We found that within 1 y, isolated branches developed into small coral colonies by growing new branches from all branch termini, in all directions. No architectural dissimilarity was assigned among the three studied genets of treatment I colonies. However, a major architectural disparity between treatment I colonies and colonies of treatments II and III was documented as the development of mirror structures from both sides of treatments II and III settings as compared to tip-borne architectures in treatment I colonies. We did not observe apical dominance since fragments grew equally from all branch sides without documented dominant polarity along branch axis. In treatment II colonies, no MP for new branches originating either from tips or from branch bases differed significantly. In treatment III colonies, growth from the cut tip areas was significantly lower compared to the base, again, suggesting lack of apical dominance in this species. Changes in branch polarity revealed genet associated plasticity, which in one of the studied genets, led to enhanced growth. Different genets exhibited canalization flexibility of growth patterns towards either lateral growth, or branch axis extension (skeletal weight and not porosity was measured). This study revealed that colony astogeny in S. pistillata is a regulated process expressed through programmed events and not directly related to simple energy trade-off principles or to environmental conditions, and that branch polarity and apical dominance do not dictate colony astogeny. Therefore, plasticity and astogenic disparities encompass a diversity of genetic (fixed and flexible) induced responses.     

One Step Membrane Incorporation of Viral Antigens as a Vaccine Candidate Against HIV

Liposomes can been used as potential immunoadjuvants, because they have the ability to elicit both a cellular mediated immune response and a humoral immune response. Studies have shown liposomes to be effective immunopotentiators in hepatitis A and influenza vaccines. For all these purposes, liposomes can be prepared by different methods. After disperging suitable membrane lipids in an aqueous phase and spontaneous formation of multilamellar large vesicles (MLV), mechanical procedures such as ultrasonication, homogenization by a French press or by other high pressure devices and, or extrusion through polycarbonate membranes with defined pore sizes lead to a reduction in size and number of lamellae of the vesicles. A second group of preparation procedures uses suitable detergents, e.g., bile salts or alkylglycosides. A third group of procedures starts with dissolving the lipids in an organic solvent and mixing it with an aqueous phase. The concentration of the organic solvent is then reduced by suitable procedures.

Here we present a new technique for the preparation of liposomes with associated membrane proteins, where lipid vesicles are formed immediately after injection into a micellar protein solution. The model membrane protein used for these studies is a truncated recombinant gp41 produced in E. coli. This viral membrane antigen is a possible candidate protein for the establishment of HIV-vaccines.

The data presented here, show an efficient and reproducible one step membrane protein encapsulation procedure into liposomes in a closed and sterile containment. We examined encapsulation efficiency, membrane protein conformation and immunogenicity of this possible liposomal vaccine candidate, which can be produced in GMP-compliant quality with the described technique.     

Surface Plasmon as a Probe of Local Field Enhancement

New method of experimental determination of local field enhancement at metal nanoparticles is suggested. It uses surface plasmon as a probe. Alternating-sign shift of surface plasmon resonance in copper nanoparticles incorporated in silica matrix has been observed under irradiation by intense femtosecond laser pulse. The red shift of plasmon observed during the action of pump pulse is interpreted as a result of change of dielectric constant of silica matrix due to optical Kerr effect in electric field of pump pulse enhanced in a vicinity of metal nanoparticles. The field enhancement factor is estimated from the value of the observed red shift of plasmon resonance.     

The reaction of Tetrazole with Phosphoramidites as a Model for the Nucleotide Coupling Step

Abstract

The mechanism of the tetrazole-activated coupling step in the synthesis of oligonucleotides via phosphorami-dites is studied with the help of model reactions.     

Determination of Variation Parameters as a Crucial Step in Designing TMT-Based Clinical Proteomics Experiments

In quantitative shotgun proteomic analyses by liquid chromatography and mass spectrometry, a rigid study design is necessary in order to obtain statistically relevant results. Hypothesis testing, sample size calculation and power estimation are fundamental concepts that require consideration upon designing an experiment. For this reason, the reproducibility and variability of the proteomic platform needs to be assessed. In this study, we evaluate the technical (sample preparation), labeling (isobaric labels), and total (biological + technical + labeling + experimental) variability and reproducibility of a workflow that employs a shotgun LC-MS/MS approach in combination with TMT peptide labeling for the quantification of peripheral blood mononuclear cell (PBMC) proteome. We illustrate that the variability induced by TMT labeling is small when compared to the technical variation. The latter is also responsible for a substantial part of the total variation. Prior knowledge about the experimental variability allows for a correct design, a prerequisite for the detection of biologically significant disease-specific differential proteins in clinical proteomics experiments.     

Heating as a rapid purification method for recovering correctly-folded thermotolerant VH and VHH domains

Background  

Recombinant antibodies from Camelidae (VHHs) are potentially useful tools for both basic research and biotechnological applications because of their small size, robustness, easy handling and possibility to refold after chemio-physical denaturation. Their heat tolerance is a particularly interesting feature because it has been recently related to both high yields during recombinant expression and selective purification of folded protein.     

Assessing Space Heating Demandon a Regional Level: Evaluation of a Bottom‐Up Model in the Scope of a Case Study

The residential sector constitutes a major energy consumer, particularly on account of its needs for space heating. Offering a high leverage potential, this sector is a suitable starting point for greenhouse gas mitigation policies. By providing predictions of the energy demand of building stocks, bottom‐up building energy models represent a first step toward deriving strategies for abatement of detrimental effects related to housing energy use. This article aims at evaluating the performance of a simplified bottom‐up housing energy model. A global sensitivity analysis was performed to study the model's structure and the impact of individual model parameters. Moreover, an extensive final energy consumption data set allowed for an in‐depth comparison of this model with primary data in the scope of a case study in a Swiss municipality. On an individual building scale, the model fails to accurately simulate the energy demand. Deviations can be attributed to a range of factors, such as variability in occupants’ behavior and problems of representativeness in the underlying statistical database. Nevertheless, such under‐ or overestimations level off on an aggregated scale. In particular, the model reproduces the overall characteristics of the residential building stock's heating demand well. It is therefore well suited as a building stock model and provides a promising basis for an extended assessment of housing energy demands. In future research work, we will apply this model to a larger region in order to study various types of settlements from a life cycle perspective and to derive targeted measures aimed at reducing environmental impacts.     

DNA-dependent RNA polymerase subunit B as a tool for phylogenetic reconstructions: Branching topology of the archaeal domain

The branching topology of the archaeal (archaebacterial) domain was inferred from sequence comparisons of the largest subunit (B) of DNA-dependent RNA polymerases (RNAP). Both the nucleic acid sequences of the genes coding for RNAP subunit B and the amino acid sequences of the derived gene products were used for phylogenetic reconstructions. Individual analysis of the three nucleotide positions of codons revealed significant inequalities with respect to guanosine and cytosine (GC) content and evolutionary rates. Only the nucleotides at the second codon positions were found to be unbiased by varied GC contents and sufficiently conserved for reliable phylogenetic reconstructions. A decision matrix was used for the combination of the results of distance matrix, maximum parsimony, and maximum likelihood methods. For this purpose the original results (sums of squares, steps, and logarithms of likelihoods) were transformed into comparable effective values and analyzed with methods known from the theory of statistical decisions. Phylogenetic invariants and statistical analysis with resampling techniques (bootstrap and jackknife) confirmed the preferred branching topology, which is significantly different from the topology known from phylogenetic trees based on 16S rRNA sequences. The preferred topology reconstructed by this analysis shows a common stem for the Methanococcales and Methanobacteriales and a separation of the thermophilic sulfur archaea from the methanogens and halophiles. The latter coincides with a unique phylogenetic location of a characteristic splitting event replacing the largest RNAP subunit of thermophilic sulfur archaea by two fragments in methanogens and halophiles. This topology is in good agreement with physiological and structural differences between the various archaea and demonstrates RNAP to be a suitable phylogenetic marker molecule. Correspondence to: H.-P. Klenk