Porous ceramics with tailored pore size and morphology as substrates for coral larval settlement

The growing demand for stony corals as ornamental aquarium animals requires defined aquacultural breeding strategies. For the sexual propagation of corals, material substrates are needed, that attract larvae and support their settlement and development. In this study, five types of highly porous ceramic materials were developed following the example of coral skeleton. The applicability of these settlement substrates was tested using larvae of the stony coral Pocillopora damicornis. Partial sintering of pressed clay pellets, freeze casting of clay and alumina-mullite based slurries and direct foaming of high alkane phase emulsified suspensions (HAPES) using alumina were employed. By the addition of mm-sized spherical polystyrene beads as sacrificial templates during freeze casting (alumina-mullite), superficial pores in the size of the larvae were created. The inorganic substrates featured open porosities between 35% (pressed clay) and 83% (foamed alumina), pore sizes ranging from nm to mm-scale and pore morphologies dominated by interparticle porosity (pressed), lamellar pores (freeze casting) and cellular pore types (direct foaming). The ceramic substrates were incubated in artificial sea water for 3 months to induce necessary biofilm formation and algae growth. Afterwards, individual substrates were exposed to 5 coral larvae, and their settlement behavior was monitored over 14 days. At the end of this period, all ceramic materials were successfully accepted as settlement substrates, with a mean settlement rate of 46.2%, and no significant differences between the substrate types. On samples with large surface superficial pores, a significantly reduced survival of settled larvae (79%) compared to the other porous materials (93–98%) was determined, suggesting a non-ideal surface topography. While alumina foam samples (HAPES) exhibit the most promising results in terms of settlement and survival of larvae, clay-based substrates provide a more economic solution for the sexual propagation of corals in aquaculture.     

Nanoparticulate Delivery of Cancer Cell Membrane Elicits Multiantigenic Antitumor Immunity

Anticancer vaccines train the body's own immune system to recognize and eliminate malignant cells based on differential antigen expression. While conceptually attractive, clinical efficacy is lacking given several key challenges stemming from the similarities between cancerous and healthy tissue. Ideally, an effective vaccine formulation would deliver multiple tumor antigens in a fashion that potently stimulates endogenous immune responses against those antigens. Here, it is reported on the fabrication of a biomimetic, nanoparticulate anticancer vaccine that is capable of delivering autologously derived tumor antigen material together with a highly immunostimulatory adjuvant. The two major components, tumor antigens and adjuvant, are presented concurrently in a fashion that maximizes their ability to promote effective antigen presentation and activation of downstream immune processes. Ultimately, it is demonstrated that the formulation can elicit potent antitumor immune responses in vivo. When combined with additional immunotherapies such as checkpoint blockades, the nanovaccine demonstrates substantial therapeutic effect. Overall, the work represents the rational application of nanotechnology for immunoengineering and can provide a blueprint for the future development of personalized, autologous anticancer vaccines with broad applicability.     

Two-way Bayesian hierarchical phylogenetic models: An application to the co-evolution of gp120 and gp41 during and after enfuvirtide treatment

Enfuvirtide (ENF) is a fusion inhibitor that prevents the entry of HIV virions into target cells. Studying the characteristics of viral evolution during treatment and after a treatment interruption can lend insight into the mechanisms of viral evolution and fitness. Although interruption of anti-HIV therapy often results in rapid emergence of an archived “wild-type” virus population, previous work from our group indicates that when only ENF is interrupted, viral gp41 continues to evolve forward and resistance mutations are lost due to back-mutation and remodeling of the envelope protein. To examine the co-evolution of gp120 and gp41 during ENF interruption we extend the Bayesian Hierarchical Phylogenetic model (HPM). Current HPMs enforce conditional independence across all outcomes while biologically all gene regions within a patient should return the same tree unless recombination confers an evolutionary selective advantage. A two-way-interaction HPM is proposed that provides middle ground between these two extremes and allows us to test for differences in evolutionary pressures across gene regions in multiple patients simultaneously. When the model is applied to a well-characterized cohort of HIV-infected patients interrupting ENF we find that across patients, the virus continued to evolve forward in both gene regions. Overall, the hypothesis of independence over dependence between the gene regions is supported. Models that allow for the examination of co-evolution over time will be increasingly important as more therapeutic classes are developed, each of which may impact other through novel and complex mechanisms.     

Tetrabutyl-tetraphenyl-diindenoperylene derivatives as alternative green donor in bulk heterojunction organic solar cells

We present the material 2,3,10,11-tetrabutyl-1,4,9,12-tetraphenyl-diindeno[1,2,3-cd:1′,2′,3′-lm] perylene (Bu4-Ph4-DIP) as alternative green donor for bulk heterojunction small molecule organic solar cells (SMOSC). It is shown that Bu4-Ph4-DIP exhibits suitable absorption characteristics to be a potential material to fill the absorption gap between the commonly used standard absorbers ZnPc and C₆₀.Devices with bulk heterojunctions of Bu4-Ph4-DIP:C₆₀ display very high open circuit voltages of 0.99 V, high fill factors of up to 57%, and experiments yield promising efficiencies of η>2%. Such green-blue absorbing SMOSC are characterized by current voltage and external quantum efficiency measurements, and material properties are studied. It is shown that the devices are responsive to substrate heating, and that different donor-acceptor mixing ratios can increase device performance. Possible influences of mixing ratio and heating on device morphology and electrical properties are discussed.     

Thermostabile Bindung von Aromastoffen an Stärke Teil 1: Bindung durch Gefriertrocknen

Thermostable Binding of Aroma Compounds to Starch. Part 1: Binding by Freeze-Drying. By freeze-drying of aqueous emulsions or suspensions of menthol, pyrazine, thymol, vanillin or peppermint oil and solutions of native or modified starches, amylose, amylopectin Or β-cyclodextrin sorbates were prepared. After heating to 180°C the aroma compounds were bound thermostable and in most cases also stable during extrusion. In general the adsorbed amounts decreased in the order cyclodextrin, amylose, potato starch, waxy maize starch, maize or tapioca starch, wheat starch, amylopectin. Some modified maize starches adsorbed greater amounts than native maize starch. Menthol and thymol were better bound to high-amylose starches, vanillin and pyrazine better to high-amylopectin starches, but vanillin best to cyclodextrin and pyrazine to maltodextrin (DE 4–5). The desorption of the aroma compounds during chewing in the mouth was limited after formation of channel inclusion compounds with amylose.     

Identifying Candidate Protein Markers of Acute Kidney Injury in Acute Decompensated Heart Failure

One-quarter of patients with acute decompensated heart failure (ADHF) experience acute kidney injury (AKI)—an abrupt reduction or loss of kidney function associated with increased long-term mortality. There is a critical need to identify early and real-time markers of AKI in ADHF; however, to date, no protein biomarkers have exhibited sufficient diagnostic or prognostic performance for widespread clinical uptake. We aimed to identify novel protein biomarkers of AKI associated with ADHF by quantifying changes in protein abundance in the kidneys that occur during ADHF development and recovery in an ovine model. Relative quantitative protein profiling was performed using sequential window acquisition of all theoretical fragment ion spectra–mass spectrometry (SWATH–MS) in kidney cortices from control sheep (n = 5), sheep with established rapid-pacing-induced ADHF (n = 8), and sheep after ~4 weeks recovery from ADHF (n = 7). Of the 790 proteins quantified, we identified 17 candidate kidney injury markers in ADHF, 1 potential kidney marker of ADHF recovery, and 2 potential markers of long-term renal impairment (differential abundance between groups of 1.2–2.6-fold, adjusted p < 0.05). Among these 20 candidate protein markers of kidney injury were 6 candidates supported by existing evidence and 14 novel candidates not previously implicated in AKI. Proteins of differential abundance were enriched in pro-inflammatory signalling pathways: glycoprotein VI (activated during ADHF development; adjusted p < 0.01) and acute phase response (repressed during recovery from ADHF; adjusted p < 0.01). New biomarkers for the early detection of AKI in ADHF may help us to evaluate effective treatment strategies to prevent mortality and improve outcomes for patients.     

Airway Delivery of Hydrogel-Encapsulated Niclosamide for the Treatment of Inflammatory Airway Disease

Repurposing of the anthelminthic drug niclosamide was proposed as an effective treatment for inflammatory airway diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Niclosamide may also be effective for the treatment of viral respiratory infections, such as SARS-CoV-2, respiratory syncytial virus, and influenza. While systemic application of niclosamide may lead to unwanted side effects, local administration via aerosol may circumvent these problems, particularly when the drug is encapsulated into small polyethylene glycol (PEG) hydrospheres. In the present study, we examined whether PEG-encapsulated niclosamide inhibits the production of mucus and affects the pro-inflammatory mediator CLCA1 in mouse airways in vivo, while effects on mucociliary clearance were assessed in excised mouse tracheas. The potential of encapsulated niclosamide to inhibit TMEM16A whole-cell Cl⁻ currents and intracellular Ca²⁺ signalling was assessed in airway epithelial cells in vitro. We achieved encapsulation of niclosamide in PEG-microspheres and PEG-nanospheres (Niclo-spheres). When applied to asthmatic mice via intratracheal instillation, Niclo-spheres strongly attenuated overproduction of mucus, inhibited secretion of the major proinflammatory mediator CLCA1, and improved mucociliary clearance in tracheas ex vivo. These effects were comparable for niclosamide encapsulated in PEG-nanospheres and PEG-microspheres. Niclo-spheres inhibited the Ca²⁺ activated Cl⁻ channel TMEM16A and attenuated mucus production in CFBE and Calu-3 human airway epithelial cells. Both inhibitory effects were explained by a pronounced inhibition of intracellular Ca²⁺ signals. The data indicate that poorly dissolvable compounds such as niclosamide can be encapsulated in PEG-microspheres/nanospheres and deposited locally on the airway epithelium as encapsulated drugs, which may be advantageous over systemic application.     

Fast start-up of a diesel fuel processor for PEM fuel cells

Fuel cell systems based on liquid fuels are particularly suitable for auxiliary power generation due to the high energy density of the fuel and its easy storage. Together with industrial partners, Oel-Waerme-Institut is developing a 3 kW_el PEM fuel cell system based on diesel steam reforming to be applied as an APU for caravans and yachts. The start-up time of a fuel cell APU is of crucial importance since a buffer battery has to supply electric power until the system is ready to take over. Therefore, the start-up time directly affects the battery capacity and consequently the system size, weight, and cost.