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Envelope tracking (ET) is a key technology improving efficiency of RF power amplifiers (PAs) and battery lifetime in mobile handsets. It has been commercialized since 4G LTE era, and is also being employed in 5G NR handsets. A supply modulator (SM) is a circuit generating power supplies of RF PAs for ET and average power tracking (APT) operations. Currently, the maximum channel BW and supported ET BW of 5G NR handset is 100MHz [1]–[4]. In a short time, over 100MHz BW will be necessary to support intra-band contiguous carrier aggregation cases of n77C/n78C/n79C in 3GPP standard [5]. The required instantaneous maximum output power of SM is about 10W which is calculated by the following parameters: 26dBm output power by power class 2 (PC2), 2dB loss of RF front-end module (FEM) due to complex operating band combinations (EN-DC for non-standalone mode, NE-DC, 2CA/3CA), 6dB higher instantaneous power due to peak-to-average power ratio (PAPR) at 1 resource block (RB), 1dB margin, and poor PA efficiency of around 33% (worst example) due to high carrier frequency of 5GHz at n79 band. The poor PA efficiency can be relaxed by high voltage PA design beyond 5V. In [1], a supply modulator with boosted output larger than battery voltage $(V_{BAT})$ is proposed, and the designed PA with 30% higher voltage shows 10% higher efficiency and broader BW owing to low impedance transformation ratio from $50 \Omega$ and small parasitic output capacitance of power cell. The challenge is how to design a supply modulator for 5G NR that can achieve both wide ET BW and high output voltage/power capability, while satisfying high efficiency, low receiver-band noise, short transition time, and multi-mode/standard operation.

In this study, a tunable electromagnetic energy harvesting system, consisting of an energy harvester and energy harvesting circuits, is developed for harnessing energy from low-frequency vibration (below 10 Hz) of a bridge, and the harvesting system is integrated with a wireless fatigue crack detection sensor. The uniqueness of the proposed energy harvesting system includes that (1) the resonance frequencies of the proposed energy harvester can be readily tuned to the resonance frequencies of a host structure, (2) an improved energy harvesting efficiency compared to other electromagnetic energy harvesters is achieved in low-frequency and vibration, and (3) high-efficiency energy harvesting circuits for rectification are developed. Furthermore, the developed energy harvesting system is integrated with an on-site wireless sensor deployed on Yeongjong Grand Bridge in South Korea for online fatigue crack detection. To the best knowledge of the authors, this is the very first study where a series of low-frequency vibration energy harvesting, rectification, and battery charging processes are demonstrated under a real field condition. The field test conducted on Yeongjong Grand Bridge, where fatigue cracks have become of a great concern, shows that the proposed energy harvester can generate a peak voltage of 2.27 V and a root mean square voltage of 0.21 V from 0.18-m/s2 root mean square acceleration at 3.05 Hz. It is estimated the proposed energy harvesting system can harness around 67.90 J for 3 weeks and an average power of 37.42 µW. The battery life of the wireless sensor is expected to extend from 1.5 to 2.2 years. The proposed energy harvesting circuits, composed of the AC–DC and boost-up converters, exhibit up to 50% battery charging efficiency when the voltage generated by the proposed energy harvester is 200 mV or higher. The proposed boost-up converter has a 100 times wider input power range than a conventional boost-up converter with a similar efficiency.

This paper presents a piezoelectric-based power management solution for battery-free wireless remote switches (BWSs). The proposed BWS IC, including a piezoelectric (PE) energy harvester and a buck converter, can collect the energy generated by a single PE-button press, and then supply that energy to a wireless transmitter to send a message. By combining a rectifier using the synchronized switch harvesting on inductor technique and a 6:1 series–parallel switched-capacitor converter, the proposed PE energy harvester can maximize the collected amount of energy, while supplying it at a low output voltage. In addition, by employing a switching-based start-up scheme and a variable ON-time pulse-frequency modulation scheme, the proposed buck converter can reduce the loss associated with charging the output capacitor during start-up, and then deliver the largest possible energy to the load, while maintaining low voltage ripples and high-power efficiency. A prototype BWS IC fabricated with high-voltage 250-nm CMOS technology was shown to be capable of harvesting a total energy of $246~\mu \text{J}$ from a single button-pressing of a 300-mm2 lead magnesium niobate-lead titanate PE disc. More than $200~\mu \text{J}$ was delivered to the load, sufficient to transmit a 4-B-long message via a 2.4-GHz wireless USB channel over a 10-m distance.

HM15211 is a novel long-acting GLP-1/GIP/Glucagon triple agonist that is being developed for the treatment of obesity and nonalcoholic fatty liver disease (NASH). Accumulating evidences have shown that obesity, type 2 diabetes, and NASH increase the risk of developing progressive neurodegenerative disease such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). In addition to peripheral contributions, each of incretins consisting HM15211 have neuroprotective effects in several brain diseases like AD, PD, and ischemia. Previously, we demonstrated that HM15211 exerted neuroprotective effects in MPTP induced subacute PD mice model. Here, we evaluated 1) the neuroprotective effects of HM15211 in chronic MPTP/probenecid PD model, and 2) the protection of AD progression in db/db mice. Chronic PD mice model was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in combination with probenecid injection, twice a week for 5 weeks and HM15211 was administered once a week for 6 weeks. Dopaminergic neuronal death by MPTP/probenecid was protected by HM15211, which was derived from anti-inflammatory and anti-oxidative stress effect by HM15211. Also HM15211 decreased alpha synuclein in striatum of chronic mice PD model. Together with these efficacies, HM15211 significantly improved the MPTP/probenecid induced motor impairments in behavior. A db/db mice are well-established diabetic model and reported that db/db mice develop hyperphosphorylation of tau as they grew older. Thus we chose db/db mice to elucidate the prophylactic effect of HM15211 on AD. After once every 2 days subcutaneous administration for 12 weeks, HM15211 reversed inflammatory cytokines and oxidative stress marker, which were increased in db/db mice. Also, increased phosphorylated tau in db/db mice was decreased by HM15211. Based on these observations, HM15211 might be a potential therapeutic option for the neurodegenerative disease. Disclosure J.A. Kim: Employee; Self; Hanmi Pharmaceutical. S. Lee: Employee; Self; Hanmi Pharmaceutical. S. Lee: Employee; Self; Hanmi Pharmaceutical. S. Jung: None. Y. Kim: Employee; Self; Hanmi Pharmaceutical. I. Choi: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. S. Kim: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical.

Obesity is an established risk factor for prediabetes, diabetes and the aggravation of preexisting diabetes by negatively affecting lipid metabolism, insulin response, and β-cell function. Thus, effective body weight loss not only prevents or delays the onset of T2DM, but also enhances the response to diabetes drugs including basal insulin in T2DM patients. Recently, we have developed a novel long-acting GLP-1/GIP/Glucagon triple agonist, HM15211, which showed potent weight loss in obese animal models. When combined with basal insulin, HM15211 might maximize the insulin response and provide additional weight loss. Here, we investigated the PK/PD properties of HM15211 and HM12460A (once weekly basal insulin developing in clinical stage) combination in animal models to evaluate the therapeutic benefits of this novel combination in diabetes. Firstly, drug-to-drug interaction (DDI) was evaluated to assess the changes in intrinsic activity and PK of the individual components. In vitro human insulin receptor phosphorylation by HM12460A was not affected by concomitant HM15211 treatment. Similarly, cAMP accumulation by HM15211 was unaffected. Analysis of PK demonstrated that the administration of HM15211 and HM12460A, either alone or in combination, did not change their extended half-lives in SD rats. Secondly, the glucose lowering and body weight loss by HM15211 in combination with HM12460A was evaluated in db/db mice. After 4 weeks treatment, a combination of HM15211 and HM12460A reduced the HbA1c more than the mono-treatment. Moreover, potent weight loss by HM15211 was well maintained even when combined with HM12460A. Based on these observation, we propose that HM15211 might be an additional combination partner for long-acting basal insulin such as HM12460A providing improved glycemic control and more favorable weight loss. Disclosure J. Kim: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. J. Lee: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. J. Choi: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. S. Jung: None. S. Lee: Employee; Self; Hanmi Pharmaceutical. I. Choi: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. S. Kim: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical.

Nonalcoholic steatohepatitis (NASH), a potential consequence of NAFLD, may lead to end stage liver disease including cirrhosis and hepatocellular carcinoma. Despite its severity and prevalence, NASH currently lacks effective treatment. In this respect, we developed a novel long-acting, GLP-1/GIP/Glucagon triple agonist, HM15211. With a unique activity profile, HM15211 could provide synergistic benefits on body weight loss and lipid profile improvement while avoiding hyperglycemic risk. Previously, we showed that HM15211 exerts potent reductions in body weight and hepatic TG (triglycerides) in DIO mice, and showed a liver preferential distribution, suggesting HM15211 as a potential treatment for NASH. Here, we evaluated the effect of HM15211 in NASH and fibrosis using MCD-diet mice with various disease induction periods. In MCD-diet mice (6 weeks induction), HM15211 treatment led to significant decrease in hepatic TG (-82.6% vs. vehicle) and TBARS (oxidative stress marker, -60.7% vs. vehicle), which coincided with significant reduction in ALT and bilirubin. Time course MRI/MRS imaging further confirmed the progressive steatosis resolution by HM15211. Furthermore, histopathological analysis indicated that HM15211 significantly reduced hepatic inflammatory gene expression and NAFLD activity score (1.3 for HM15211, 3.4 for liraglutide, and 2.7 for vehicle). To further evaluate the therapeutic potential in fibrosis, MCD-diet mice was used for an extended period (10 weeks induction) to achieve overt liver fibrosis. In line with NASH improvement, HM15211 successfully resolved liver fibrosis as demonstrated in histological evaluation. Histological improvements were accompanied by a remarkable decrease in disease biomarkers including hepatic hydroxyproline. Based on these observations, HM15211 may offer a therapeutic potential for NASH and fibrosis as well as obesity. Disclosure I. Choi: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. J. Kim: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. J. Lee: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. E. Park: Employee; Self; Hanmi Pharmaceutical. Y. Kim: Employee; Self; Hanmi Pharmaceutical. S. Jung: None. S. Kim: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical.

This paper presents the design of a low-power, low area 256-radix 16-bit crossbar switch employing a 2D Hyper-X network topology. The Hyper-X crossbar switch realizes the high radix of 256 by hierarchically combining a set of 4-radix sub-switches and applies three modifications to the basic Hyper-X topology in order to mitigate the adverse scaling of power consumption and propagation delay with the increasing radix. For instance, by restricting the directions in which signals can be routed, by restricting the ports to which signals can be connected, and by replacing the column-wise routes with diagonal routes, the fanout of each circuit node can be substantially reduced from 256 to 4~8. The proposed 256-radix, 16-bit crossbar switch is designed in a 65 ㎚ CMOS and occupies the total area of 0.93×1.25 ㎟. The simulated worst-case delay and power dissipation are 641 ps and 13.01 W when operating at a 1.2 V supply and 1 ㎓ frequency. In comparison with the state-of-the-art designs, the proposed crossbar switch design achieves the best energy-delay efficiency of 2.203 cycle/ns?fJ?λ².

Interferon-α (IFN-α) has been widely used for the treatment of infections due to the hepatitis C virus (HCV). Because of the short half-life of IFN-α in serum, it must be administered three times per week. To increase the half-life of IFN-α, the immunoglobulin G4 (IgG4) Fc fragment (HMC001) was conjugated with human IFN-α-2b to develop a long-acting IFN-α-2b, HM10660A. An analysis of the antiviral efficacy of HM10660A in a human hepatocyte-engrafted mouse model found that HM10660A reduced serum HCV titers more effectively than a commercially available peginterferon α-2a (PEGASYS®) and IFN-α-2b. Pharmacokinetic (PK) and pharmacodynamic (PD) studies of HM10660A using monkeys demonstrated that the half-life of HM10660A was approximately 2-fold longer than commercially available peginterferon α-2a, which is approved for a once-weekly regimen. Moreover, the IFN-mediated induction profiles of neopterin and 2', 5'-oligoadenylate synthase (OAS) in normal cynomolgus monkeys indicated that HM10660A had enhanced antiviral activity and a prolonged duration of action compared with peginterferon α-2a. Considering the improved PK and PD properties, HM10660A can most likely be dosed every two or four weeks, providing superior antiviral efficacy and convenience for patients with HCV.

This paper proposes an algorithm that can maximize the total harvested energy of a single-inductor buck-boost converter operating with multiple input energy sources. It does so by dynamically adjusting the turn-on times and allocating the available time slots for the individual input sources in such a way that all the sources require equal turn-off times for the buck-boost converter to meet the zero-current switching (ZCS) condition. The prototype energy-harvesting IC fabricated in 0.25µm CMOS can charge a 3.3V lithium battery with a delivered power ranging 0.5–5mW utilizing up to four different energy sources simultaneously. The controller itself consumes only 8µW. The experimental results show that the proposed time-slot optimization algorithm can achieve the overall combined power efficiency up to 73.3%, which is a 23% higher than the one with fixed, equal time-slots.

Improved glucagon-like peptide-1 (GLP-1) receptor activation is considered one of the most effective targets for antidiabetic therapy. For this purpose, we modified the GLP-1 analog of exendin-4 using two fatty acids (FA) either lauric acid (LUA, C12) or palmitic acid (PAA, C16) at its two lysine residues, to produce; Lys(12)-FA-Exendin-4 (FA-M2), Lys(27)-FA-Exendin-4 (FA-M1), or Lys(12,27)-diBA-Exendin-4 (FA-Di). The structural, biological, and pharmaceutical characteristics of these exendin-4 analogs were then investigated. Biological activity tests demonstrated that LUA-M1 had well-preserved in vivo antidiabetic activity and in vitro insulinotropic activity with minimum GLP-1 receptor binding affinity loss as compared with exendin-4. Furthermore, pharmacokinetic studies in rats revealed that s.c. administration of LUA-M1 significantly enhanced pharmacokinetic parameters, such as, elimination half-life, mean residence time, and AUC values as compared with exendin-4. The protracted antidiabetic effects of LUA-M1 were also confirmed by prolonged normoglycemia observed in type 2 diabetic mice (20nmol/mouse single injection of exendin-4 or LUA-M1 induced normoglycemia for 6 or 24h, respectively). These findings suggest that FA conjugated exendin-4s should be considered potential candidates for the treatment of diabetes.

To develop an effective long-acting antidiabetic, the GLP-1 analogue of exendin-4 was modified with three different bile acids (BAs; cholic, deoxycholic, or lithocholic acid), at its two lysine residues. The biological, pharmaceutical, and physicochemical characteristics of these exendin-4 analogues were carefully investigated. Biological activity tests demonstrated that the monobile acid substitutions of exendin-4 showed well preserved receptor binding efficacy without noticeable insulinotropic or antidiabetic activity loss. However, physicochemical and pharmacokinetic studies revealed that the albumin-binding properties and in vivo elimination half-lives of BAM1-Ex4s (Lys(27)-BA-Ex4s) were significantly enhanced by increasing the hydrophobicities of the conjugated BAs. Furthermore, the protracted antidiabetic effects of the BAM1-Ex4s were also verified by the prolonged restoration of normoglycemia in type 2 diabetic mice. Accordingly, the present study suggests that the derivatization of exendin-4 with BAs offers a means of producing long-acting GLP-1 receptor agonists for type 2 diabetic therapy.

Robot system is widely used in unmanned exploration or investigation because it can be dangerous or impossible to explore a certain unknown area such as distant planet. For this purpose, highly intelligent single robot systems are generally used. But thinking of disabled situation, a lot of swarm-bots can be alternative to a single highly intelligent robot. This paper reports an implementation of swarm-bots on Player/Stage platform using Pyro. The swarm-bots implemented in this paper searching for a set of objects in an area with irregular barriers and bringing them to the home location where they start. A simple map construction algorithm is devised and implemented. According to the implementation, the swarm-bots can effectively collect the objects in the exploration area.