Reduced complexity for sound zones with subband block adaptive filters and a loudspeaker line array.

Sound zones are used to reproduce individual audio content to multiple people in a room using a set of loudspeakers with controllable input signals. To allow the reproduction of individual audio to dynamically change, e.g., due to moving listeners, changes in the number of listeners, or changing room transfer functions, an adaptive formulation is proposed. This formulation is based on frequency domain block adaptive filters and given room transfer functions. To reduce computational complexity, the system is extended to subband processing without cross-adaptive filters. The computational savings come from recognizing that sound zones consist of part-solutions which are inherently band limited, hence, several subbands can be ignored. To validate the theoretical findings, a 27-channel loudspeaker array was constructed, and measurements were performed in anechoic and reflective environments. The results show that the subband solution performs identically to a full-rate solution but at a reduced computational complexity.

Performance of low-frequency sound zones with very fast room impulse response measurements.

Sound zone methods aim to control the sound field produced by an array of loudspeakers to render a given audio content in specific areas while making it almost inaudible in others. At low frequencies, control filters are based on information of the electro-acoustical path between loudspeakers and listening areas, contained in the room impulse responses (RIRs). This information can be acquired wirelessly through ubiquitous networks of microphones. In that case and for real-time applications in general, short acquisition and processing times are critical. In addition, limiting the amount of data that should be retrieved and processed can also reduce computational demands. Furthermore, such a framework would enable fast adaptation of control filters in changing acoustic environments. This work explores reducing the amount of time and information required to compute control filters when rendering and updating low-frequency sound zones. Using real RIR measurements, it is demonstrated that in some standard acoustic rooms, acquisition times on the order of a few hundred milliseconds are sufficient for accurately rendering sound zones. Moreover, an additional amount of information can be removed from the acquired RIRs without degrading the performance.

Nanovesicles displaying functional linear and branched oligomannose self-assembled from sequence-defined Janus glycodendrimers.

Cell surfaces are often decorated with glycoconjugates that contain linear and more complex symmetrically and asymmetrically branched carbohydrates essential for cellular recognition and communication processes. Mannose is one of the fundamental building blocks of glycans in many biological membranes. Moreover, oligomannoses are commonly found on the surface of pathogens such as bacteria and viruses as both glycolipids and glycoproteins. However, their mechanism of action is not well understood, even though this is of great potential interest for translational medicine. Sequence-defined amphiphilic Janus glycodendrimers containing simple mono- and disaccharides that mimic glycolipids are known to self-assemble into glycodendrimersomes, which in turn resemble the surface of a cell by encoding carbohydrate activity via supramolecular multivalency. The synthetic challenge of preparing Janus glycodendrimers containing more complex linear and branched glycans has so far prevented access to more realistic cell mimics. However, the present work reports the use of an isothiocyanate-amine "click"-like reaction between isothiocyanate-containing sequence-defined amphiphilic Janus dendrimers and either linear or branched oligosaccharides containing up to six monosaccharide units attached to a hydrophobic amino-pentyl linker, a construct not expected to assemble into glycodendrimersomes. Unexpectedly, these oligoMan-containing dendrimers, which have their hydrophobic linker connected via a thiourea group to the amphiphilic part of Janus glycodendrimers, self-organize into nanoscale glycodendrimersomes. Specifically, the mannose-binding lectins that best agglutinate glycodendrimersomes are those displaying hexamannose. Lamellar "raft-like" nanomorphologies on the surface of glycodendrimersomes, self-organized from these sequence-defined glycans, endow these membrane mimics with high biological activity.

Radiolabeled Nanocarriers as Theranostics-Advancement from Peptides to Nanocarriers.

Endogenous targeted radiotherapy is emerging as an integral modality to treat a variety of cancer entities. Nevertheless, despite the positive clinical outcome of the treatment using radiolabeled peptides, small molecules, antibodies, and nanobodies, a high degree of hepatotoxicity and nephrotoxicity still persist. This limits the amount of dose that can be injected. In an attempt to mitigate these side effects, the use of nanocarriers such as nanoparticles (NPs), dendrimers, micelles, liposomes, and nanogels (NGs) is currently being explored. Nanocarriers can prolong circulation time and tumor retention, maximize radiation dosage, and offer multifunctionality for different targeting strategies. In this review, the authors first provide a summary of radiation therapy and imaging and discuss the new radiotracers that are used preclinically and clinically. They then highlight and identify the advantages of radio-nanomedicine and its potential in overcoming the limitations of endogenous radiotherapy. Finally, the review points to the ongoing efforts to maximize the use of radio-nanomedicine for efficient clinical translation.

Mimicking the Natural Basement Membrane for Advanced Tissue Engineering.

Advancements in the field of tissue engineering have led to the elucidation of physical and chemical characteristics of physiological basement membranes (BM) as specialized forms of the extracellular matrix. Efforts to recapitulate the intricate structure and biological composition of the BM have encountered various advancements due to its impact on cell fate, function, and regulation. More attention has been paid to synthesizing biocompatible and biofunctional fibrillar scaffolds that closely mimic the natural BM. Specific modifications in biomimetic BM have paved the way for the development of in vitro models like alveolar-capillary barrier, airway models, skin, blood-brain barrier, kidney barrier, and metastatic models, which can be used for personalized drug screening, understanding physiological and pathological pathways, and tissue implants. In this Review, we focus on the structure, composition, and functions of in vivo BM and the ongoing efforts to mimic it synthetically. Light has been shed on the advantages and limitations of various forms of biomimetic BM scaffolds including porous polymeric membranes, hydrogels, and electrospun membranes This Review further elaborates and justifies the significance of BM mimics in tissue engineering, in particular in the development of in vitro organ model systems.

A facile method for grafting functional hydrogel films on PTFE, PVDF, and TPX polymers.

The use of polymeric materials in biomedical applications requires a judicious control of surface properties as they are directly related to cellular interactions and biocompatibility. The most desired chemical surface properties include hydrophilicity and the presence of functional groups for surface modification. In this work, we describe a method to graft a highly stable, ultra-thin, amine-functional hydrogel layer onto highly inert surfaces of poly(tetrafluoroethylene) (PTFE), poly(vinylidene fluoride) (PVDF), and poly(4-methyl-1-pentene) (PMP or TPX). Covalent grafting is realized with hydrophilic poly(vinylamine-co-acetamide)s by C-H insertion crosslinking (CHic) chemistry initiated by UV light. These polyvinylamides carry tetrafluorophenyl azide groups as photo or thermo activated binding sites and contain further free amine groups, which can be used to bind peptides such as biological ligands, polysaccharides, or other hydrogel layers. The covalently bound surface layers resist intensive Soxhlet extraction confirming the stability of the coating. Fluorescent staining verified the accessibility of free primary amine groups, which can be used for the functionalization of the surface with bioactive molecules. The coating demonstrates hydrophobic wetting behavior when conditioned in air and hydrophilic wetting behavior when conditioned in water showing the presence of loosely crosslinked polymer chains that can re-orient. We believe that the reported application of CHic for the surface modification of fluorinated polymers like PTFE and PVDF as well as TPX can form the basis for advanced biocompatible and biofunctional surface engineering.

Encapsulation of hydrophobic components in dendrimersomes and decoration of their surface with proteins and nucleic acids.

Reconstructing the functions of living cells using nonnatural components is one of the great challenges of natural sciences. Compartmentalization, encapsulation, and surface decoration of globular assemblies, known as vesicles, represent key early steps in the reconstitution of synthetic cells. Here we report that vesicles self-assembled from amphiphilic Janus dendrimers, called dendrimersomes, encapsulate high concentrations of hydrophobic components and do so more efficiently than commercially available stealth liposomes assembled from phospholipid components. Multilayer onion-like dendrimersomes demonstrate a particularly high capacity for loading low-molecular weight compounds and even folded proteins. Coassembly of amphiphilic Janus dendrimers with metal-chelating ligands conjugated to amphiphilic Janus dendrimers generates dendrimersomes that selectively display folded proteins on their periphery in an oriented manner. A modular strategy for tethering nucleic acids to the surface of dendrimersomes is also demonstrated. These findings augment the functional capabilities of dendrimersomes to serve as versatile biological membrane mimics.

Encoding biological recognition in a bicomponent cell-membrane mimic.

Self-assembling dendrimers have facilitated the discovery of periodic and quasiperiodic arrays of supramolecular architectures and the diverse functions derived from them. Examples are liquid quasicrystals and their approximants plus helical columns and spheres, including some that disregard chirality. The same periodic and quasiperiodic arrays were subsequently found in block copolymers, surfactants, lipids, glycolipids, and other complex molecules. Here we report the discovery of lamellar and hexagonal periodic arrays on the surface of vesicles generated from sequence-defined bicomponent monodisperse oligomers containing lipid and glycolipid mimics. These vesicles, known as glycodendrimersomes, act as cell-membrane mimics with hierarchical morphologies resembling bicomponent rafts. These nanosegregated morphologies diminish sugar-sugar interactions enabling stronger binding to sugar-binding proteins than densely packed arrangements of sugars. Importantly, this provides a mechanism to encode the reactivity of sugars via their interaction with sugar-binding proteins. The observed sugar phase-separated hierarchical arrays with lamellar and hexagonal morphologies that encode biological recognition are among the most complex architectures yet discovered in soft matter. The enhanced reactivity of the sugar displays likely has applications in material science and nanomedicine, with potential to evolve into related technologies.

Design-functionality relationships for adhesion/growth-regulatory galectins.

Glycan-lectin recognition is assumed to elicit its broad range of (patho)physiological functions via a combination of specific contact formation with generation of complexes of distinct signal-triggering topology on biomembranes. Faced with the challenge to understand why evolution has led to three particular modes of modular architecture for adhesion/growth-regulatory galectins in vertebrates, here we introduce protein engineering to enable design switches. The impact of changes is measured in assays on cell growth and on bridging fully synthetic nanovesicles (glycodendrimersomes) with a chemically programmable surface. Using the example of homodimeric galectin-1 and monomeric galectin-3, the mutual design conversion caused qualitative differences, i.e., from bridging effector to antagonist/from antagonist to growth inhibitor and vice versa. In addition to attaining proof-of-principle evidence for the hypothesis that chimera-type galectin-3 design makes functional antagonism possible, we underscore the value of versatile surface programming with a derivative of the pan-galectin ligand lactose. Aggregation assays with N,N'-diacetyllactosamine establishing a parasite-like surface signature revealed marked selectivity among the family of galectins and bridging potency of homodimers. These findings provide fundamental insights into design-functionality relationships of galectins. Moreover, our strategy generates the tools to identify biofunctional lattice formation on biomembranes and galectin-reagents with therapeutic potential.

Tuning the Elasticity of Nanogels Improves Their Circulation Time by Evading Immune Cells.

Peptide receptor radionuclide therapy is used to treat solid tumors by locally delivering radiation. However, due to nephro- and hepato-toxicity, it is limited by its dosage. To amplify radiation damage to tumor cells, radiolabeled nanogels can be used. We show that by tuning the mechanical properties of nanogels significant enhancement in circulation half-life of the gel could be achieved. We demonstrate why and how small changes in the mechanical properties of the nanogels influence its cellular fate. Nanogels with a storage modulus of 37 kPa were minimally phagocytosed by monocytes and macrophages compared to nanogels with 93 kPa modulus. Using PET/CT a significant difference in the blood circulation time of the nanogels was shown. Computer simulations affirmed the results and predicted the mechanism of cellular uptake of the nanogels. Altogether, this work emphasizes the important role of elasticity even for particles that are inherently soft such as nano- or microgels.

Thiolactone-Functional Pullulan for In Situ Forming Biogels.

Gelation in the presence of cells with minimum cytotoxicity is highly desirable for materials with applications in tissue engineering. Herein, the naturally occurring polysaccharide pullulan is functionalized with thiolactones that undergo ring-opening addition of amines. As a result, the modified pullulan can be cross-linked with diamines and/or amine-containing biological substrates enhancing the system's versatility (e.g., gelatin and cell-binding ligands GHK/GRGDS). Thiolactone degrees of substitution of 2.5 or 5.0 mol % are achieved, and respective hydrogels exhibit mesh sizes of 27.8 to 49.1 nm. Cell proliferation studies on chosen gels (G' ≅ 500 Pa, over 14 days) demonstrate that for normal human dermal fibroblasts (NHDFs), both gelatin and GRGDS equally support cell proliferation, while in the case of hepatocytes (HepG2), the presence of GRGDS and GHK improve cell proliferation 10-fold compared to gelatin. Cells remain viable and in one instance were successfully encapsulated by in situ gelation, altogether confirming the mild and biocompatible nature of this strategy to produce biogels using biologically active substrates as cross-linkers.

Microgel that swims to the beat of light.

Complementary to the quickly advancing understanding of the swimming of microorganisms, we demonstrate rather simple design principles for systems that can mimic swimming by body shape deformation. For this purpose, we developed a microswimmer that could be actuated and controlled by fast temperature changes through pulsed infrared light irradiation. The construction of the microswimmer has the following features: (i) it is a bilayer ribbon with a length of 80 or 120 [Formula: see text]m, consisting of a thermo-responsive hydrogel of poly-N-isopropylamide coated with a 2-nm layer of gold and equipped with homogeneously dispersed gold nanorods; (ii) the width of the ribbon is linearly tapered with a wider end of 5 [Formula: see text]m and a tip of 0.5 [Formula: see text]m; (iii) a thickness of only 1 and 2 [Formula: see text]m that ensures a maximum variation of the cross section of the ribbon along its length from square to rectangular. These wedge-shaped ribbons form conical helices when the hydrogel is swollen in cold water and extend to a filament-like object when the temperature is raised above the volume phase transition of the hydrogel at [Formula: see text]. The two ends of these ribbons undergo different but coupled modes of motion upon fast temperature cycling through plasmonic heating of the gel-objects from inside. Proper choice of the IR-light pulse sequence caused the ribbons to move at a rate of 6 body length/s (500 [Formula: see text]m/s) with the wider end ahead. Within the confinement of rectangular container of 30 [Formula: see text]m height and 300 [Formula: see text]m width, the different modes can be actuated in a way that the movement is directed by the energy input between spinning on the spot and fast forward locomotion.

Exploring functional pairing between surface glycoconjugates and human galectins using programmable glycodendrimersomes.

Precise translation of glycan-encoded information into cellular activity depends critically on highly specific functional pairing between glycans and their human lectin counter receptors. Sulfoglycolipids, such as sulfatides, are important glycolipid components of the biological membranes found in the nervous and immune systems. The optimal molecular and spatial design aspects of sulfated and nonsulfated glycans with high specificity for lectin-mediated bridging are unknown. To elucidate how different molecular and spatial aspects combine to ensure the high specificity of lectin-mediated bridging, a bottom-up toolbox is devised. To this end, negatively surface-charged glycodendrimersomes (GDSs), of different nanoscale dimensions, containing sulfo-lactose groups are self-assembled in buffer from a synthetic sulfatide mimic: Janus glycodendrimer (JGD) containing a 3'-O-sulfo-lactose headgroup. Also prepared for comparative analysis are GDSs with nonsulfated lactose, a common epitope of human membranes. These self-assembled GDSs are employed in aggregation assays with 15 galectins, comprising disease-related human galectins, and other natural and engineered variants from four families, having homodimeric, heterodimeric, and chimera architectures. There are pronounced differences in aggregation capacity between human homodimeric and heterodimeric galectins, and also with respect to their responsiveness to the charge of carbohydrate-derived ligand. Assays reveal strong differential impact of ligand surface charge and density, as well as lectin concentration and structure, on the extent of surface cross-linking. These findings demonstrate how synthetic JGD-headgroup tailoring teamed with protein engineering and network assays can help explain how molecular matchmaking operates in the cellular context of glycan and lectin complexity.

Poly(vinylamine-co-N-isopropylacrylamide) linear polymer and hydrogels with tuned thermoresponsivity.

The fabrication of functional hydrogels with tuned thermoresponsivity is a major challenge. To meet this challenge we copolymerize N-isopropylacrylamide (NIPAm) with N-vinylformamide (NVF) in different ratios with the formamide group being subsequently selectively hydrolyzed to the corresponding amine (VAm). The copolymers are crosslinked with phenylcarbonate telechelic glycol. The influence of the NIPAm : VAm ratio on the thermoresponsitiviy is investigated in terms of absorbance, rheology, NMR spectroscopy, relaxometry, and diffusometry. Phase transition temperatures, change in the entropy of the polymer-water system, and width of the transition in the process of coil-to-globule and swollen-to-collapsed network transitions were evaluated by a two state model and Boltzmann sigmoidal function.

Tolerability of facial electrostimulation in healthy adults and patients with facial synkinesis.

PURPOSE: To evaluate optimal stimulation parameters with regard to discomfort and tolerability for transcutaneous electrostimulation of facial muscles in healthy participants and patients with postparetic facial synkinesis. METHODS: Two prospective studies were performed. First, single pulse monophasic stimulation with rectangular pulses was compared to triangular pulses in 48 healthy controls. Second, 30 healthy controls were compared to 30 patients with postparetic facial synkinesis with rectangular pulse form. Motor twitch threshold, tolerability threshold, and discomfort were assessed using a numeric rating scale at both thresholds. RESULTS: Discomfort at motor threshold was significantly lower for rectangular than for triangular pulses. Average motor and tolerability thresholds were higher for patients than for healthy participants. Discomfort at motor threshold was significantly lower for healthy controls compared to patients. Major side effects were not seen. CONCLUSIONS: Surface electrostimulation for selective functional and tolerable facial muscle contractions in patients with postparetic facial synkinesis is feasible.

Sound field reconstruction in rooms: Inpainting meets super-resolution.

In this paper, a deep-learning-based method for sound field reconstruction is proposed. The possibility to reconstruct the magnitude of the sound pressure in the frequency band 30-300 Hz for an entire room by using a very low number of irregularly distributed microphones arbitrarily arranged is shown. Moreover, the approach is agnostic to the location of the measurements in the Euclidean space. In particular, the presented approach uses a limited number of arbitrary discrete measurements of the magnitude of the sound field pressure in order to extrapolate this field to a higher-resolution grid of discrete points in space with a low computational complexity. The method is based on a U-net-like neural network with partial convolutions trained solely on simulated data, which itself is constructed from numerical simulations of Green's function across thousands of common rectangular rooms. Although extensible to three dimensions and different room shapes, the method focuses on reconstructing the two-dimensional plane of a rectangular room from measurements of the three-dimensional sound field. Experiments using simulated data together with an experimental validation in a real listening room are shown. The results suggest a performance which may exceed conventional reconstruction techniques for a low number of microphones and computational requirements.

Membrane-Mimetic Dendrimersomes Engulf Living Bacteria via Endocytosis.

There is much interest in developing vesicular microcompartments from natural and synthetic amphiphiles, enabling programmable interactions with living matter. Of particular interest is the development of vesicles capable of endocytosis of living bacteria. Despite the complexity of this process, theoretical studies predict that the endocytosis of prolate micro-objects is possible without the need of active cell machinery if the energy released upon bacterial adhesion to the membrane surpasses the energy required to bend the membrane. Nonetheless, natural liposomes and synthetic polymersomes fail to sufficiently recapitulate membrane properties to perform this advanced function. Here we report the engulfment of living bacteria into endosomes by cell-like dendrimersomes assembled from Janus dendrimers. Full engulfment occurred in less than a minute after contact. The process is driven by the adhesion of the bacterium to the dendrimersome's membrane by ultraweak interactions, comparable to those utilized by nature. The key to success relies on the combination of high flexibility and stability of the dendrimersomes. The key properties of the dendrimersomes are programmed into the molecular structures of their building blocks. The ability to support endocytosis highlights opportunities for the design and programming of dendrimersomes in biomedical research.

A Light-Driven Microgel Rotor.

The current understanding of motility through body shape deformation of micro-organisms and the knowledge of fluid flows at the microscale provides ample examples for mimicry and design of soft microrobots. In this work, a 2D spiral is presented that is capable of rotating by non-reciprocal curling deformations. The body of the microswimmer is a ribbon consisting of a thermoresponsive hydrogel bilayer with embedded plasmonic gold nanorods. Such a system allows fast local photothermal heating and nonreciprocal bending deformation of the hydrogel bilayer under nonequilibrium conditions. It is shown that the spiral acts as a spring capable of large deformations thanks to its low stiffness, which is tunable by the swelling degree of the hydrogel and the temperature. Tethering the ribbon to a freely rotating microsphere enables rotational motion of the spiral by stroboscopic irradiation. The efficiency of the rotor is estimated using resistive force theory for Stokes flow. This research demonstrates microscopic locomotion by the shape change of a spiral and may find applications in the field of microfluidics, or soft microrobotics.

Screening Libraries of Amphiphilic Janus Dendrimers Based on Natural Phenolic Acids to Discover Monodisperse Unilamellar Dendrimersomes.

Natural, including plant, and synthetic phenolic acids are employed as building blocks for the synthesis of constitutional isomeric libraries of self-assembling dendrons and dendrimers that are the simplest examples of programmed synthetic macromolecules. Amphiphilic Janus dendrimers are synthesized from a diversity of building blocks including natural phenolic acids. They self-assemble in water or buffer into vesicular dendrimersomes employed as biological membrane mimics, hybrid and synthetic cells. These dendrimersomes are predominantly uni- or multilamellar vesicles with size and polydispersity that is predicted by their primary structure. However, in numerous cases, unilamellar dendrimersomes completely free of multilamellar assemblies are desirable. Here, we report the synthesis and structural analysis of a library containing 13 amphiphilic Janus dendrimers containing linear and branched alkyl chains on their hydrophobic part. They were prepared by an optimized iterative modular synthesis starting from natural phenolic acids. Monodisperse dendrimersomes were prepared by injection and giant polydisperse by hydration. Both were structurally characterized to select the molecular design principles that provide unilamellar dendrimersomes in higher yields and shorter reaction times than under previously used reaction conditions. These dendrimersomes are expected to provide important tools for synthetic cell biology, encapsulation, and delivery.

Aqueous microgels modified with photosensitive wedge-shaped amphiphilic molecules: synthesis, structure and photochemical behaviour.

Aqueous microgels based on poly(N-vinylcaprolactam) with reversible temperature-induced volume transition are promising "smart" materials for various applications. In this work, the microgels are modified via acid-base interaction by wedge-shaped amphiphilic sulfonic acid molecules with alkyl chains of different lengths and an azobenzene group. In contrast to the pristine microgel the modified microgels retain colloidal stability in water and show different responses to the change of temperature and pH. The azobenzene group in the ligand molecules acts as a spectroscopic and kinetic probe sensing the microenvironment inside the microgel particles. Thus, the observed hyperchromicity upon heating suggests the enhancement of hydrophobicity with the increase of temperature. The hydrophobicity of the microgel interior increases with the increase of the modification degree as indicated by the increase of activation energy of the thermal Z/E isomerization of the azobenzene group.