Focused Design of Novel Cyclic Peptides Endowed with GABARAP-Inhibiting Activity

(1) Background: Disfunctions in autophagy machinery have been identified in various conditions, including neurodegenerative diseases, cancer, and inflammation. Among mammalian autophagy proteins, the Atg8 family member GABARAP has been shown to be greatly involved in the autophagy process of prostate cancer cells, supporting the idea that GABARAP inhibitors could be valuable tools to fight the progression of tumors. (2) Methods: In this paper, starting from the X-ray crystal structure of GABARAP in a complex with an AnkirinB-LIR domain, we identify two new peptides by applying in silico drug design techniques. The two ligands are synthesized, biophysically assayed, and biologically evaluated to ascertain their potential anticancer profile. (3) Results: Two cyclic peptides (WC8 and WC10) displayed promising biological activity, high conformational stability (due to the presence of disulfide bridges), and K_d values in the low micromolar range. The anticancer assays, performed on PC-3 cells, proved that both peptides exhibit antiproliferative effects comparable to those of peptide K1, a known GABARAP inhibitor. (4) Conclusions: WC8 and WC10 can be considered new GABARAP inhibitors to be employed as pharmacological tools or even templates for the rational design of new small molecules.     

Microstructure and Thermoelectric Properties of Dense YB<Subscript>22</Subscript>C<Subscript>2</Subscript>N Samples Fabricated Through Spark Plasma Sintering

Dense samples of the higher boride YB₂₂C₂N have been fabricated through the spark plasma sintering (SPS) method with different sintering aids. YB₂₂C₂N is a representative of a series of newly discovered rare-earth borocarbonitrides, which may be the long-awaited n-type counterpart of boron carbide, “B₄C.” The effect of Si, SiC, Al, and TiC additions on the sintering process of YB₂₂C₂N has been studied. The best sintered bodies with densities higher than 90% of theoretical density were obtained by means of SPS at 1700°C. We show that the additive choice and pressure have an effect on grain size and density. An investigation of the effect of atmosphere on the sintering behavior has also been carried out. It was found that sinterability is enhanced under nitrogen atmosphere. Thermoelectric properties of the materials sintered with additives have been evaluated, and we discuss their dependences on the fabrication process route.     

Ultrafast reflective optical Kerr demultiplexer using polarisation rotation mirror

A novel all-optical switching scheme in a reflective mode is proposed and its stable 60 Gbit/s operation at 1.307 mu m demonstrated. The scheme uses a 90 degrees polarisation rotation on reflection to compensate for birefringence phase turbulence in the Kerr media.<>     

A Bit-Error Rate Measurement and Error Analysis of Wireline Data Transmission using Current Source Model for Single Event Effect under Irradiation Environment

A high-speed wireline interfaces, e.g. LVDS (Low Voltage Differential Signaling), are widely used in the aerospace field for powerful computing in artificial satellites and aircraft [19]. This paper describes Bit Error Rate (BER) prediction methodology for wireline data transmission under irradiation environment at the design stage of data transmitter, which is useful in proactively determining if the design circuit meets the BER criteria of the target system. Using a custom-designed LVDS transmitter (TX) to enhance latch-up immunity [42], the relationship between transistor size and BER has been analyzed with focusing on Single Event Effect (SEE) as a cause of the bit error. The measurement was executed under ⁸⁴Kr¹⁷⁺ exposure of 322.0 MeV at various flux condition from 1?×?10³ to 5?×?10⁵ count/cm²/sec using cyclotron facility. For the analysis of the bit error, circuit simulation by SPICE was utilized with expressing the irradiation environment by a current source model. The current source model represents a single event strike into the circuit at drain and substrate junctions in bulk MOSFETs. For the construction of the current source model, a charge collection was simulated at the single particle strike with the creation of 3D Technology CAD (TCAD) models for the MOS devices of bulk transistor process technology. The simulation result of the charge correction was converted to a simple time-domain equation, and the single-event current source model was produced using the equation. The single-event current source was applied to SPICE simulation at bias current related circuits in the LVDS transmitter, then simulation results are carefully verified whether the output data is disturbed enough to cause bit errors on wireline data transmission. By the simulation, sensitive MOSFETs have been specified and a sum of the gate area for these MOSFETs has 29% better correlation than the normal evaluation index (sum of the drain area) by comparison to the actual BER measurement. Through the precise revelation of the sensitive area by SPICE simulation using the current model, it became possible to estimate BER under irradiation environment at the pre-fabrication design stage.

     

FM/PWM control scheme in class DE inverter

This paper presents a new control scheme for a Class DE inverter, that is, frequency modulation/pulsewidth modulation (FM/PWM) control. Further, the FM/PWM controlled Class DE inverter is analyzed and we clarify performance characteristics. Since the FM/PWM controlled inverter has two control parameters, namely, the switching frequency and the switch-on duty ratio, it has one more degree of freedom for the control than the inverter with the conventional control scheme. The increased degree of freedom is used to minimize the switching losses. Therefore, it is possible to control the output power with high power-conversion efficiency for wide-range control. Carrying out the circuit experiments, we confirm that the experimental results agree well with the theoretical predictions quantitatively. For example, the proposed controlled inverter can control the output voltage from 56% to 191% of the optimum one, which is designed for 1.8 W at 1.0 MHz, with maintaining over 90% power-conversion efficiency.     

Development of a standing style transfer system "ABLE" for disabled lower limbs

We have developed a standing style transfer system, or "ABLE," for a person with disabled legs. It allows travel in a standing posture even on uneven ground, a standing up motion from a chair, and allows the stairs. ABLE consists of three modules: a pair of telescopic crutches, a powered lower extremity orthosis, and a pair of mobile platforms. We present here the conceptual design of ABLE and the motion of each module. Cooperative operations using the three modules are discussed through simulations. The standing up motion from a chair and ascending the stairs, however, have problems with adaptability to the environment and safety, because it executes the movement that has till now relied on telescopic crutches. To solve these problems, we propose a new motion technique and compare it with the previous one. In this paper, some experimental results are also presented.     

A channel-erasing 1.8-V-only 32-Mb NOR flash EEPROM with a bitlinedirect sensing scheme

A 1.8-V-only 32-Mb NOR flash EEPROM has been developed based on the 0.25-μm triple-well double-metal CMOS process. A channel-erasing scheme has been implemented to realize a cell size of 0.49 μm² , the smallest yet reported for 0.25-μm CMOS technology. A block decoder circuit with a novel erase-reset sequence has been designed for the channel-erasing operation. A bitline direct sensing scheme and a wordline boosted voltage pooling method have been developed to obtain high-speed reading operation at low voltage. An access time of 90 ns at 1.8 V has been realized     

Wavelength-independent operation of EA-modulator integratedwavelengthselectable microarray light sources

In this letter, we have simultaneously fabricated five wavelength-selectable microarray light sources (WSLs), each having a different wavelength range integrated with an electroabsorption (EA) modulator on a single wafer. We also introduced a novel device configuration scheme for wavelength-independent modulation. The five EA-WSLs fully covered the entire C-band and had a low uniform threshold current of 6 ± 1 mA at 25°C. Wavelength-independent extinction characteristics were obtained over a tuning wavelength range of 8 nm, and 2.5-Gb/s transmission over 600 km was successfully achieved     

Discovering Homophily in Online Social Networks

Mobile Networks and Applications - During the last ten years, Online Social Networks (OSNs) have increased their popularity by becoming part of the real life of users. Despite their tremendous...