Human talkers change their voices to elicit specific trait percepts.

The voice is a variable and dynamic social tool with functional relevance for self-presentation, for example, during a job interview or courtship. Talkers adjust their voices flexibly to their situational or social environment. Here, we investigated how effectively intentional voice modulations can evoke trait impressions in listeners (Experiment 1), whether these trait impressions are recognizable (Experiment 2), and whether they meaningfully influence social interactions (Experiment 3). We recorded 40 healthy adult speakers' whilst speaking neutrally and whilst producing vocal expressions of six social traits (e.g., likeability, confidence). Multivariate ratings of 40 listeners showed that vocal modulations amplified specific trait percepts (Experiments 1 and 2), which could be explained by two principal components relating to perceived affiliation and competence. Moreover, vocal modulations increased the likelihood of listeners choosing the voice to be suitable for corresponding social goals (i.e., a confident rather than likeable voice to negotiate a promotion, Experiment 3). These results indicate that talkers modulate their voice along a common trait space for social navigation. Moreover, beyond reactive voice changes, vocal behaviour can be strategically used by talkers to communicate subtle information about themselves to listeners. These findings advance our understanding of non-verbal vocal behaviour for social communication.

Investigating the Integration of Nonwoven Carbon Fibers for Mechanical Enhancement in Compression Molded Fiber-Reinforced Polymer Bipolar Plates.

The demand for polymer composite solutions in bipolar plates for polymer electrolyte membrane fuel cells (PEMFCs) has risen due to advantages over metal plates such as longer lifetime, weight reduction, corrosion resistance, flexible manufacturing, freedom of design, and cost-effectiveness. The challenge with polymer composites is achieving both sufficient electrical conductivity and mechanical stability with high filler content. A carbon fiber fleece as reinforcement in a graphite-filled polypropylene (PP) matrix was investigated for use as bipolar plate material with increased mechanical and sufficient conductive properties. Plates with a thickness of 1 mm containing four layers of fleece impregnated in the PP-graphite compound were produced in a compression molding process. Particle and fiber interactions were investigated via microscopy. The plates were characterized with respect to the electrical conductivity and mechanical stability. High electric conductivity was reached for fiber-reinforced and plain PP-graphite compound plates, with increased filler content leading to a higher conductivity. The contact resistance remained largely unaffected by surface etching as no polymeric skin layer formed during compression molding. Fiber-reinforced plates exhibit twice the tensile strength, a significantly higher tensile modulus, and an increased elongation at break, compared to PP filled only with graphite.

Electrostatic anti-CD33-antibody-protamine nanocarriers as platform for a targeted treatment of acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a fatal clonal hematopoietic malignancy, which results from the accumulation of several genetic aberrations in myeloid progenitor cells, with a worldwide 5-year survival prognosis of about 30%. Therefore, the development of more effective therapeutics with novel mode of action is urgently demanded. One common mutated gene in the AML is the DNA-methyltransferase DNMT3A whose function in the development and maintenance of AML is still unclear. To specifically target "undruggable" oncogenes, we initially invented an RNAi-based targeted therapy option that uses the internalization capacity of a colorectal cancer specific anti-EGFR-antibody bound to cationic protamine and the anionic siRNA. Here, we present a new experimental platform technology of molecular oncogene targeting in AML. METHODS: Our AML-targeting system consists of an internalizing anti-CD33-antibody-protamine conjugate, which together with anionic molecules such as siRNA or ibrutinib-Cy3.5 and cationic free protamine spontaneously assembles into vesicular nanocarriers in aqueous solution. These nanocarriers were analyzed concerning their physical properties and relevant characteristics in vitro in cell lines and in vivo in xenograft tumor models and patient-derived xenograft leukemia models with the aim to prepare them for translation into clinical application. RESULTS: The nanocarriers formed depend on a balanced electrostatic combination of the positively charged cationic protamine-conjugated anti-CD33 antibody, unbound cationic protamine and the anionic cargo. This nanocarrier transports its cargo safely into the AML target cells and has therapeutic activity against AML in vitro and in vivo. siRNAs directed specifically against two common mutated genes in the AML, the DNA-methyltransferase DNMT3A and FLT3-ITD lead to a reduction of clonal growth in vitro in AML cell lines and inhibit tumor growth in vivo in xenotransplanted cell lines. Moreover, oncogene knockdown of DNMT3A leads to increased survival of mice carrying leukemia patient-derived xenografts. Furthermore, an anionic derivative of the approved Bruton's kinase (BTK) inhibitor ibrutinib, ibrutinib-Cy3.5, is also transported by this nanocarrier into AML cells and decreases colony formation. CONCLUSIONS: We report important results toward innovative personalized, targeted treatment options via electrostatic nanocarrier therapy in AML.

Biaxial Elongation Behavior in Partially Molted State of Two-Layer Sheets Containing Postconsumer Material.

Due to the lack of raw material and forced by political demand, an increasing percentage of postconsumer materials (PCR) shall be used in all processing methods in polymer technology. Thermoforming, as one of the oldest polymer-processing methods, has special requirements regarding the melt stability at high temperatures. Low melt stability affects the thermoforming in a negative manner, as the low stiffness leads the sheet to sag during the heating phase. In this study, two-layer sheets are used in order to improve melt stability of PCR material. The focus is placed on the influence of rheological properties on the biaxial stretching behavior of mono- and two-layer sheets in partially molted state. In order to create a stabilizing layer, two different thermoformable virgin materials with a melt flow rate (MFR) of 3 g/10 min and 6 g/10 min were chosen. The second layer consists of instable PCR materials with a MFR of 16 g/10min and 50 g/10 min. Rheological investigations, molecular characterization and biaxial stretching tests are used to show the benefit of two-layer sheets for processing PCR material under elongational stress. The results show that the use of two-layer sheets can improve the biaxial stretching properties, so that two-layer sheets can offer a significant potential in the processing of PCR materials in thermoforming.

Two Layer Sheets for Processing Post-Consumer Materials.

An increasing percentage of post-consumer materials (PCR) is becoming more and more important in all processing methods in polymer technology, also due to the lack of raw materials and political demands. Very special requirements are placed on material properties such as viscosities in extrusion. Low viscosities and the presence of particles affect extrusion in a negative manner. In this study, the use of multilayer sheets is determined to both ensure extrudability and contribute to a significant improvement in surface qualities. The focus is placed on the influence of viscosity and particles on mono- und multilayer sheet quality. Therefore, two different virgin materials with a melt flow rate (MFR) of 3 g/10 min and 6 g/10 min and two different PCR materials with a MFR of 16 g/10 min and 50 g/10 min are processed both in monolayers and in two layer sheets. Rheological investigations, optical analysis, and film thickness distributions are used to show the relationship between matrix viscosity and particles. The results show that the use of multilayer extrusion can improve both extrudability and sheet quality, so that multilayer sheets can offer a significant potential in the processing of PCR materials.

Targeted siRNA nanocarrier: a platform technology for cancer treatment.

The small arginine-rich protein protamine condenses complete genomic DNA into the sperm head. Here, we applied its high RNA binding capacity for spontaneous electrostatic assembly of therapeutic nanoparticles decorated with tumour-cell-specific antibodies for efficiently targeting siRNA. Fluorescence microscopy and DLS measurements of these nanocarriers revealed the formation of a vesicular architecture that requires presence of antibody-protamine, defined excess of free SMCC-protamine, and anionic siRNA to form. Only these complex nanoparticles were efficient in the treatment of non-small-cell lung cancer (NSCLC) xenograft models, when the oncogene KRAS was targeted via EGFR-mediated delivery. To show general applicability, we used the modular platform for IGF1R-positive Ewing sarcomas. Anti-IGR1R-antibodies were integrated into an antibody-protamine nanoparticle with an siRNA specifically against the oncogenic translocation product EWS/FLI1. Using these nanoparticles, EWS/FLI1 knockdown blocked in vitro and in vivo growth of Ewing sarcoma cells. We conclude that these antibody-protamine-siRNA nanocarriers provide a novel platform technology to specifically target different cell types and yet undruggable targets in cancer therapy by RNAi.

Tumor-Cell-Specific Targeting of Ibrutinib: Introducing Electrostatic Antibody-Inhibitor Conjugates (AiCs).

Ibrutinib is an inhibitor of Bruton's tyrosine kinase that has been approved for the treatment of patients with chronic lymphocytic leukemia, mantle cell lymphoma and Waldenstrom's macroglobulinemia and is connected with toxicities. To minimize its toxicities, we linked ibrutinib to a cell-targeted, internalizing antibody. To this end, we synthesized a poly-anionic derivate, ibrutinib-Cy3.5, that retains full functionality. This anionic inhibitor is complexed by our anti-CD20-protamine targeting conjugate and free protamine, and thereby spontaneously assembles into an electrostatically stabilized vesicular nanocarrier. The complexation led to an accumulation of the drug driven by the CD20 antigen internalization to the intended cells and an amplification of its pharmacological effectivity. In vivo, we observed a significant enrichment of the drug in xenograft lymphoma tumors in immune-compromised mice and a significantly better response to lower doses compared to the original drug.