Deviation from the normal mode expansion in a coupled graphene-nanomechanical system

We optomechanically measure the vibrations of a nanomechanical system made of a graphene membrane suspended on a silicon nitride nanoresonator. When probing the thermal noise of the coupled nanomechanical device, we observe a significant deviation from the normal mode expansion. It originates from the heterogeneous character of mechanical dissipation over the spatial extension of coupled eigenmodes, which violates one of the fundamental prerequisite for employing this commonly used description of the nanoresonators' thermal noise. We subsequently measure the local mechanical susceptibility and demonstrate that the fluctuation-dissipation theorem still holds and permits a proper evaluation of the thermal noise of the nanomechanical system. Since it naturally becomes delicate to ensure a good spatial homogeneity at the nanoscale, this approach is fundamental to correctly describe the thermal noise of nanomechanical systems which ultimately impact their sensing capacity

Selection for life-history traits to maximize population growth in an invasive marine species

Species establishing outside their natural range, negatively impacting local ecosystems, are of increasing global concern. They often display life-history features characteristic for r-selected populations with fast growth and high reproduction rates to achieve positive population growth rates (r) in invaded habitats. Here, we demonstrate substantially earlier maturation at a 2 orders of magnitude lower body mass at first reproduction in invasive compared to native populations of the comb jelly Mnemiopsis leidyi. Empirical results are corroborated by a theoretical model for competing life-history traits that predicts maturation at the smallest possible size to optimize r, while individual lifetime reproductive success (R0), optimized in native populations, is near constant over a large range of intermediate maturation sizes. We suggest that high variability in reproductive tactics in native populations is an underappreciated determinant of invasiveness, acting as substrate upon which selection can act during the invasion proces

Conditional human VEGF‐mediated vascularization in chicken embryos using a novel temperature‐inducible gene regulation (TIGR) system

Advanced heterologous transcription control systems for adjusting desired transgene expression are essential for gene function assignments, drug discovery, manufacturing of difficult to produce protein pharmaceuticals and precise dosing of gene‐based therapeutic interventions. Conversion of the Streptomyces albus heat shock response regulator (RheA) into an artificial eukaryotic transcription factor resulted in a vertebrate thermosensor (CTA; cold‐inducible transactivator), which is able to adjust transcription initiation from chimeric target promoters (PCTA) in a low‐temperature‐ inducible manner. Evaluation of the temperature‐dependent CTA-PCTA interaction using a tailored ELISA‐like cell‐free assay correlated increased affinity of CTA for PCTA with temperature downshift. The temperature‐inducible gene regulation (TIGR) system enabled tight repression in the chicken bursal B‐cell line DT40 at 41°C as well as precise titration of model product proteins up to maximum expression at or below 37°C. Implantation of microencapsulated DT40 cells engineered for TIGR‐controlled expression of the human vascular endothelial growth factor A (hVEGF121) provided low‐temperature‐induced VEGF‐mediated vascularization in chicken embryo

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation

Cytotoxic tumor targeting with scFv antibody-modified liposomes

Specific targeting of liposome-formulated cytotoxic drugs or antigens to receptors expressed selectively on target cells represents an effective strategy for increasing the pharmacological efficacy of the delivered molecules. We have developed a feasible technique to selectively attach antibodies and fragments thereof, but also small-mol-wt ligands such as peptides, carbohydrates, or any molecules that recognize and bind target antigens or receptors to the surface of small unilamellar liposomes. Our concept is based on the site-specific functionalization of the ligands to be attached to the liposomes by thiol groups. These thiol groups can easily be introduced to antibodies or peptides by addition of cysteines, preferably at sites that do not interfere with the receptor binding domains. Optimally, the site-specific modification is introduced at the C-terminal end of the ligand, separated by an inert spacer sequence located between the thiols and the specific part of the ligand. The thiol-reactive molecules on the liposome surface are maleimides that are linked to phospholipids composing the liposome bilayer membrane. We illustrate the coupling method of a functionalized single-chain antibody fragment with binding specificity to ED-B fibronectin, an isoform of fibronectin exclusively expressed in tumor tissues, to long circulating small unilamellar poly(ethylene glycol) liposomes

CRM Online-Games : Chance oder Flop?

Spieltrieb ist auch im Web Trumpf. Als neues Marketing-Instrument sind Online Games im Aufbruch und blicken einer rosigen Zukunft entgegen. Die Hauptanwendungen heute liegen in den Bereichen Kundenbindung und Brandmanagement. Customer Relations Management mit neuen Vorzeichen