Specific targeting of human caspases using designed ankyrin repeat proteins

Caspases play important roles in cell death, differentiation, and proliferation. Due to their high homology, especially of the active site, specific targeting of a particular caspase using substrate analogues is very difficult. Although commercially available small molecules based on peptides are lacking high specificity due to overlapping cleavage motives between different caspases, they are often used as specific tools. We have selected designed ankyrin repeat proteins (DARPins) against human caspases 1-9 and identified high-affinity binders for the targeted caspases, except for caspase 4. Besides previously reported caspase-specific DARPins, we generated novel DARPins (D1.73, D5.15, D6.11, D8.1, D8.4, and D9.2) and confirmed specificity for caspases 1, 5, 6, and 8 using a subset of caspase family members. In addition, we solved the crystal structure of caspase 8 in complex with DARPin D8.4. This binder interacts with non-conserved residues on the large subunit, thereby explaining its specificity. Structural analysis of this and other previously published crystal structures of caspase/DARPin complexes depicts two general binding areas either involving active site forming loops or a surface area laterally at the large subunit of the enzyme. Both surface areas involve non-conserved surface residues of caspase

Monolithic solder-on nanoporous Si-Cu contacts for stretchable silicone composite sensors

We report a method of creating solderable, mechanically robust, electrical contacts to interface (soft) silicone-based strain sensors with conventional (hard) solid-state electronics using a nanoporous Si-Cu composite. The Si-based solder-on electrical contact consists of a copper-plated nanoporous Si top surface formed through metal-assisted chemical etching and electroplating, and a smooth Si bottom surface which can be covalently bonded onto silicone-based strain sensors through plasma bonding. We investigated the mechanical and electrical properties of the contacts proposed under relevant ranges of mechanical stress for applications in physiological monitoring and rehabilitation. We also produced a series of proof-of-concept devices, including a wearable respiration monitor, leg band for exercise monitoring and Squeeze-ball for monitoring rehabilitation of patients with hand injuries or neurological disorders, to demonstrate the mechanical robustness and versatility of the technology developed, in real-world applications

Autocatalytic metallization of fabrics using Si ink, for biosensors, batteries and energy harvesting

Commercially available metal inks are mainly designed for planar substrates (for example, polyethylene terephthalate foils or ceramics), and they contain hydrophobic polymer binders that fill the pores in fabrics when printed, thus resulting in hydrophobic electrodes. Here, a low‐cost binder‐free method for the metallization of woven and nonwoven fabrics is presented that preserves the 3D structure and hydrophilicity of the substrate. Metals such as Au, Ag, and Pt are grown autocatalytically, using metal salts, inside the fibrous network of fabrics at room temperature in a two‐step process, with a water‐based silicon particle ink acting as precursor. Using this method, (patterned) metallized fabrics are being enabled to be produced with low electrical resistance (less than 3.5 Ω sq−1). In addition to fabrics, the method is also compatible with other 3D hydrophilic substrates such as nitrocellulose membranes. The versatility of this method is demonstrated by producing coil antennas for wireless energy harvesting, Ag–Zn batteries for energy storage, electrochemical biosensors for the detection of DNA/proteins, and as a substrate for optical sensing by surface enhanced Raman spectroscopy. In the future, this method of metallization may pave the way for new classes of high‐performance devices using low‐cost fabrics

Self-powered ultrasensitive and highly stretchable temperature-strain sensing composite yarns

With the emergence of stretchable/wearable devices, functions, such as sensing, energy storage/harvesting, and electrical conduction, should ideally be carried out by a single material, while retaining its ability to withstand large elastic deformations, to create compact, functionally-integrated and autonomous systems. A new class of trimodal, stretchable yarn-based transducer formed by coating commercially available Lycra® yarns with PEDOT:PSS is presented. The material developed can sense strain (first mode), and temperature (second mode) and can power itself thermoelectrically (third mode), eliminating the need for an external power-supply. The yarns were extensively characterized and obtained an ultrahigh (gauge factor ∼3.6 × 105, at 10–20% strain) and tunable (up to about 2 orders of magnitude) strain sensitivity together with a very high strain-at-break point (up to ∼1000%). These PEDOT:PSS-Lycra yarns also exhibited stable thermoelectric behavior (Seebeck coefficient of 15 μV K−1), which was exploited both for temperature sensing and self-powering (∼0.5 μW, for a 10-couple module at ΔT ∼ 95 K). The produced material has potential to be interfaced with microcontroller-based systems to create internet-enabled, internet-of-things type devices in a variety of form factors

Методика оценки лавинного питания (на примере трёх ледников Тянь-Шаня)

The contribution of snow avalanches to the seasonal snow accumulation on a glacier is among the least studied components of the glacier’s mass balance. The methods for the numerical assessment of avalanche accumulation are still under development, which is related to poor avalanche data availability and difficulties in obtaining such data on most of mountain glaciers. We propose a possible methodology for the numerical assessment of snow avalanche contribution to snow accumulation at mountain glaciers based on DEM and weather data analysis using GIS and numerical modeling of snow avalanches. The developed methodology consists of the following steps: terrain analysis; weather data analysis; snow avalanche volume assessment during an analyzed balance year; numerical simulation of snow avalanches using RAMMS; evaluation of snow avalanches contribution into a glacier accumulation. The proposed methodology was tested on three glaciers located in the Inner Tien Shan: Batysh Sook, № 354 and Karabatkak during the 2015/16 balance year. To evaluate snow avalanche contribution to the seasonal accumulation, we reconstructed avalanche release zones that were most probably active during the 2015/16 balance year and corresponding snow fracture height in each of these zones. The numerical simulations of most probable released snow avalanches during the winter period 2015/16 using avalanche dynamics software RAMMS were performed and compared with the field observations and UAV orthophoto image from July 2016. The outlines of avalanches deposits were realistically reproduced by RAMMS according to the results of field observation. The estimated share of snow avalanche contribution to the accumulation on the research glaciers during the 2015/16 balance year turned out to be: Batysh Sook – 7,4±2,5%; № 354 – 2,2±0,7%; Karabatkak – 10,8±3,6% of the total accumulation. The next step would be to test the proposed methodology based on the data and regional dependences from the Inner Tien Shan in other mountainous regions. This methodology is applicable in the regions where DEMs, regular meteorological observations as well as data on the regional avalanche formation factors are available.Предложена новая методика количественной оценки лавинного питания ледников, основанная на анализе рельефа и данных метеорологических наблюдений с использованием методов геоинформационного картографирования и математического моделирования. Рассмотрены результаты её применения на трёх ледниках Тянь-Шаня: Западный Суёк, № 354, Карабаткак