• Biomedical Science Letters
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• v.27 no.3
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• pp.121-133
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• 2021

Antibody-drug conjugates (ADCs) are drawing much interest due to its great potential to be one of the important options in cancer treatments. ADCs are acting like a magic bullet which delivers cytotoxic drugs specifically to cancerous cells throughout the body, thus attacks these cells, while not harming healthy cells. ADCs are complex molecules that are composed of an antibody having targeting capability and linked-payload or cytotoxic drug killing cancerous cells. The key factors of the success in the development of ADC are selection of appropriate antibody, cytotoxic payload and linker for conjugation. Recently there was considerable progress in ADCs development, and a large number of ADCs gained US FDA approval. About 80 new ADCs are under active clinical studies. In this review we present a brief introduction of the US-FDA approved ADCs and global situation in the clinical studies of ADC pipelines. We address an overview on each component of an ADC design such as target antigens, payloads, linkers, conjugation methods, drug antibody ratio. In addition, we discuss on the trend of ADC market where global big pharmas and domestic biopharmaceutical companies are competing to develop safer and more effective ADCs.

• JSTS:Journal of Semiconductor Technology and Science
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• v.14 no.2
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• pp.189-197
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• 2014

This work proposes a 12b 100 MS/s $0.11{\mu}m$ CMOS three-step hybrid pipeline ADC for high-speed communication and mobile display systems requiring high resolution, low power, and small size. The first stage based on time-interleaved dual-channel SAR ADCs properly handles the Nyquist-rate input without a dedicated SHA. An input sampling clock for each SAR ADC is synchronized to a reference clock to minimize a sampling-time mismatch between the channels. Only one residue amplifier is employed and shared in the proposed ADC for the first-stage SAR ADCs as well as the MDAC of back-end pipeline stages. The shared amplifier, in particular, reduces performance degradation caused by offset and gain mismatches between two channels of the SAR ADCs. Two separate reference voltages relieve a reference disturbance due to the different operating frequencies of the front-end SAR ADCs and the back-end pipeline stages. The prototype ADC in a $0.11{\mu}m$ CMOS shows the measured DNL and INL within 0.38 LSB and 1.21 LSB, respectively. The ADC occupies an active die area of $1.34mm^2$ and consumes 25.3 mW with a maximum SNDR and SFDR of 60.2 dB and 69.5 dB, respectively, at 1.1 V and 100 MS/s.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.1
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• pp.33-40
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• 2021

Recently, antibody-drug conjugates (ADCs) are used to deliver efficient cytotoxic payloads selectively in cancer cells. In the designing of an ADC, the antibody is connected to a toxic payload via a covalent linker, which helps to solubilizes the typical hydrophobic payload as well as stabilizes the linkage over circulation. The development of the linkers for the antibody drug conjugate is still in demand. Initially, the acid, disulfide, and cathepsin-sensitive ADCs attracted considerable attention for the delivery of a potent cytotoxic payload but suffer from instability in human and mouse plasma with a short half-life. In addition, It also suffer from a solubility issue that induces aggregation, which is the major problem in their development. ADCs associated with sulfatase and phosphatase cleavable linker are highly soluble due to the anionic nature of sulfate and phosphate groups. The ADCs also showed high stability in human and mouse plasma. Therefore, to overcome these limitations, sulfatase and phosphatase cleavable linkers were developed. This review focuses on the recently reported advantages of sulfatase and phosphatase cleavable linkers for ADCs.

• Nuclear Engineering and Technology
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• v.56 no.6
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• pp.2131-2140
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• 2024

The chloride-induced stress corrosion cracking (CISCC) is one of the major integrity concerns in dry storage canisters made of austenitic stainless steels (ASSs). In this study, an advanced duplex stainless steel (DSS) with a composition of Fe-19Cr-4Ni-2.5Mo-4.5Mn (ADCS) was developed and its performance was compared with that of commercial ASS and DSS alloys. The chemical composition of ADCS was determined to obtain greater pitting and CISCC resistance as well as a proper combination of strength and ductility. Then, the thermomechanical processing (TMP) condition was applied, which resulted in higher strength than ASSs (304L SS and 316L SS) and better ductility than DSSs (2101 LDSS and 2205 DSS). The potentiodynamic polarization and electrochemical impedance spectra (EIS) results represented the better pitting corrosion resistance of ADCS compared to 304L SS and 316L SS by forming a better passive layer. The CISCC tests using four-point loaded specimens showed that cracks were initiated at 24 h for 304L SS and 144 h for 316L SS, while crack was not found until 1008 h for ADCS. Overall, the developed alloy, ADCS, showed better combination of CISCC resistance and mechanical properties as dry storage canister materials than commercial alloys.

• Molecules and Cells
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• v.43 no.10
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• pp.889-897
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• 2020

K-RAS is frequently mutated in human lung adenocarcinomas (ADCs), and the p53 pathway plays a central role in cellular defense against oncogenic K-RAS mutation. However, in mouse lung cancer models, oncogenic K-Ras mutation alone can induce ADCs without p53 mutation, and loss of p53 does not have a significant impact on early K-Ras-induced lung tumorigenesis. These results raise the question of how K-Ras-activated cells evade oncogene surveillance mechanisms and develop into lung ADCs. RUNX3 plays a key role at the restriction (R)-point, which governs multiple tumor suppressor pathways including the p14^ARF-p53 pathway. In this study, we found that K-Ras activation in a very limited number of cells, alone or in combination with p53 inactivation, failed to induce any pathologic lesions for up to 1 year. By contrast, when Runx3 was inactivated and K-Ras was activated by the same targeting method, lung ADCs and other tumors were rapidly induced. In a urethane-induced mouse lung tumor model that recapitulates the features of K-RAS-driven human lung tumors, Runx3 was inactivated in both adenomas (ADs) and ADCs, whereas K-Ras was activated only in ADCs. Together, these results demonstrate that the R-point-associated oncogene surveillance mechanism is abrogated by Runx3 inactivation in AD cells and these cells cannot defend against K-Ras activation, resulting in the transition from AD to ADC. Therefore, K-Ras-activated lung epithelial cells do not evade oncogene surveillance mechanisms; instead, they are selected if they occur in AD cells in which Runx3 has been inactivated.

• Journal of Positioning, Navigation, and Timing
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• v.6 no.4
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• pp.195-203
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• 2017

A 2U cube satellite called SNUGLITE has been developed by GNSS Research Laboratory in Seoul National University. Its main mission is to perform actual operation by mounting dual-frequency global positioning system (GPS) receivers. Its scientific mission aims to observe space environments and collect data. It is essential for a cube satellite to control an Earth-oriented attitude for reliable and successful data transmission and reception. To this end, an attitude estimation and control algorithm, Attitude Determination and Control System (ADCS), has been implemented in the on-board computer (OBC) processor in real time. In this paper, the Extended Kalman Filter (EKF) was employed as the attitude estimation algorithm. For the attitude control technique, the Linear Quadratic Gaussian (LQG) was utilized. The algorithm was verified through the processor in the loop simulation (PILS) procedure. To validate the ADCS algorithm in the ground, the experimental verification via a single axis Hardware-in-the-loop simulation (HILS) was used due to the simplicity and cost effectiveness, rather than using the 3-axis HILS verification (Schwartz et al. 2003) with complex air-bearing mechanism design and high cost.

• Fisheries and Aquatic Sciences
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• v.25 no.11
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• pp.537-548
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• 2022

Apparent digestibility coefficients (ADCs) of dry matter, crude protein, crude lipid, nitrogen-free extract, energy and essential amino acids in animal-based feed ingredients were determined for olive flounder (Paralichthys olivaceus). A reference diet (RF) was formulated to contain 1.0% chromic oxide (Cr₂O₃) as an inert indicator. Nine test diets were formulated to contain RF and one of the feed ingredients (pollock meal [PM], jack mackerel meal [JMM], anchovy meal [AM], cod meal [CM], sardine meal [SM], sand eel meal [SEM], tuna meal [TM], meat meal [MM] and squid liver meal [SLM]) at a 7:3 ratio in each diet designated as PM, JMM, AM, CM, SM, SEM, TM, MM and SLM, respectively. Olive flounder, averaging 150 ± 8.0 g, were stocked at a density of 25 fish per tank in 400-L fiberglass tanks attached with fecal collection columns. Feces were collected from triplicate groups of fish one time a day for four weeks. Dry matter and crude protein ADCs of CM and SEM were significantly higher than the other tested ingredients. Lipid ADCs of JMM, CM and SEM were significantly higher than the other test ingredients. Energy ADCs of CM and SEM were significantly higher than that of the other tested ingredients. The availability of amino acids in CM was generally higher than the other animal protein sources. PM exhibited the lowest amino acid availability among the treatments. Interestingly, MM exhibited significantly higher nutrient digestibility than several marine-based ingredients. However, CM and SEM are seeming to be highly digestible and effective to use in olive flounder diet compared to the other tested ingredients. Overall, the results of this study provide information about the bioavailability of nutrients and energy in animal feedstuffs to apply when formulating cost-effective practical feeds for olive flounder.

• Journal of Microbiology and Biotechnology
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• v.25 no.1
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• pp.66-73
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• 2015

The pabS gene of Agaricus bisporus 02 encoding a putative PABA synthase was cloned, and then the recombinant protein was expressed in Escherichia coli BL21 under the control of the T7 promoter. The enzyme with an N-terminal GST tag or His tag, designated GST-AbADCS or His-AbADCS, was purified with glutathione Sepharose 4B or Ni Sepharose 6 Fast Flow. The enzyme was an aminodeoxychorismate synthase, and it was necessary to add with an aminodeoxychorismate lyase for synthesizing PABA. AbADCS has maximum activity at a temperature of approximately 25℃ and pH 8.0. Magnesium or manganese ions were necessary for the enzymatic activity. The Michaelis-Menten constant for chorismate was 0.12 mM, and 2.55 mM for glutamine. H₂O₂ did distinct damage on the activity of the enzyme, which could be slightly recovered by Hsp20. Sulfydryl reagents could remarkably promote its activity, suggesting that cysteine residues are essential for catalytic function.

• Earthquakes and Structures
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• v.3 no.5
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• pp.749-766
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• 2012

Structural control through integration of passive damping devices within the building structure has been increasingly implemented internationally in the last years and has proven to be a most promising strategy for earthquake safety. In the present paper an alternative configuration of an innovative energy dissipation mechanism that consists of slender tension only bracing members with closed loop and a hysteretic damper is investigated in its dynamic behavior. The implementation of the adaptable dual control system, ADCS, in frame structures enables a dual function of the component members, leading to two practically uncoupled systems, i.e., the primary frame, responsible for the normal vertical and horizontal forces and the closed bracing-damper mechanism, for the earthquake forces and the necessary energy dissipation. Three representative international earthquake motions of differing frequency contents, duration and peak ground acceleration have been considered for the numerical verification of the effectiveness and properties of the SDOF systems with the proposed ADCS-configuration. The control mechanism may result in significant energy dissipation, when the geometrical and mechanical properties, i.e., stiffness and yield force of the integrated damper, are predefined. An optimum damper ratio, DR, defined as the ratio of the stiffness to the yield force of the hysteretic damper, is proposed to be used along with the stiffness factor of the damper's- to the primary frame's stiffness, in order for the control mechanism to achieve high energy dissipation and at the same time to prevent any increase of the system's maximum base shear and relative displacements. The results are summarized in a preliminary design methodology for ADCS.

• IEIE Transactions on Smart Processing and Computing
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• v.3 no.4
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• pp.161-166
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• 2014

An accurate gain-of-two amplifier, which successfully reduces the capacitor mismatch error is proposed. This amplifier has similar circuit complexity and linearity improvement to the capacitor error-averaging technique, but operates with two clock phases just like the conventional pipeline stage. This makes it suitable for high-speed, high-resolution analog-to-digital converters (ADCs). Two ADC architectures employing the proposed accurate gain-of-two amplifier are also presented. The simulation results show that the proposed ADCs can achieve 15-bit linearity with 8-bit capacitor matching.