博士(学術)

Political connections are considered a valuable resource in not only high-corruption countries but also low-corruption countries. This dissertation investigates the relationship between political connections and Sharia compliance, aiming to deepen understanding of the nature of political connections, as Sharia compliance prohibits engaging in corruption. Specifically, I analyze whether: 1) political connections and Sharia compliance affect merger and acquisition (M&A) performance; 2) connections to politicians affect the market response to firms' inclusion in or exclusion from the Indonesia Sharia Stock Index (ISSI); 3) political connections and Sharia compliance have been valuable during the COVID-19 pandemic; and 4) political connections affect firms' environmental performance. This dissertation comprises six chapters. Chapters 1 and 6 respectively introduce and conclude this dissertation. The remaining four chapters (i.e., Chapters 2-5) are essays on the empirical relationship between political connections and Sharia compliance. In Chapter 2, I study the impact of political connections and Sharia compliance on M&A performance, focusing on M&A deals in Indonesia during 2010-2016. I find that while political connections can improve market reactions to M&A announcements, Sharia compliance has a positive but insignificant impact on M&A performance. I further find that there is a substitution relationship between Sharia compliance and political connections: Sharia -compliant firms with political connections have poorer M&A performance than non-Sharia-compliant firms with political connections. Chapter 3 examines market responses to firms' addition to and removal from the ISSI and how political connections influence those market responses. I employ two kinds of analysis. First, using the event-study methodology, I measure abnormal returns surrounding the announcement of each firm's addition to or removal from the ISSI. Second, to more precisely identify the relationship between political connections and Sharia compliance, I use a pooled regression analysis. The results show that neither addition to nor removal from the ISSI produces abnormal returns for Indonesian firms, indicating that investors are little concerned with ISSI reconstitutions. Furthermore, political connections increase firms' value before inclusion in the ISSI, but the benefits of these connections are lost after their addition to the index. Chapter 4 offers novel evidence by investigating the value of political connections and Sharia compliance during the COVID-19 pandemic. I use the event-study methodology to measure the stock market reaction to the COVID-19 pandemic, and conduct a pooled regression analysis to more precisely identify the value of political connections and Sharia compliance during the pandemic. I find that a stock market anomaly occurred during the COVID-19 pandemic in Indonesia, in that the pandemic had a positive impact on the stock market. I also find that there was value for firms in being Sharia-compliant during the pandemic when the government announced tax incentives for firms. In Chapter 5, I investigate the relationship between political connections and the environmental performance of Sharia -compliant firms. I use a unique sample of firms covered by Indonesia's Program for Pollution Control Evaluation and Rating during 2013-2019. I find that political connections are less (more) valuable for Sharia-compliant firms (non-Sharia-compliant firms) m enhancing their environmental performance.

The role of optimization can be found in almost all aspects of human life. Optimization is common in but not limited to the fields of engineering, economics, design, and planning. Although the optimization problems to be solved change, the optimization goal never changes. That is to find effective solutions efficiently. In modern optimization studies, the metaheuristic algorithm has been one of the most interesting methods, considering the demands of a reasonable computational time. Many metaheuristic algorithms have been introduced. However, based on the number of tentative solutions used in the search process, metaheuristic algorithms can be categorized into (1) population-based or (2) single-trajectory-based algorithms. The searching with singletrajectory-based metaheuristic algorithms manipulates and modifies a single solution point in every iteration. In contrast, the population-based metaheuristic algorithms combine a set of solution points to create new solutions in every iteration. A metaheuristic algorithm usually consists of two components, i.e., exploration and exploitation. Exploration means searching for solutions in the global space. In contrast, exploitation means searching for a solution by focusing on a small area or an area near an already known solution. The single-trajectory-based metaheuristic algorithm is exploitation-oriented. On the other side, the population-based metaheuristic algorithm is exploration-oriented because of searching by many points distributed on all search spaces. Balance settings between exploration and exploitation are needed to produce good solutions. In fact, most population-based algorithms will encounter decreasing in exploration and become too exploitation-oriented as the iteration increase. Any metaheuristic algorithm applies parameters to control the behavior. However, the parameters usually do not provide a good intuition of the rate of exploration and exploitation. Hence, reaching a balance between them is hard to predict just by the algorithm parameters. This dissertation proposes a conceptual design combining the spy algorithm and B-VNS. The spy algorithm is a population-based metaheuristic algorithm that mimics the strategy of a group of spies, the spy ring. The spy algorithm is a new concept with the main idea to ensure the benefit of exploration and exploitation, and cooperative and non-cooperative searches always exist. This goal is implemented by utilizing three kinds of dedicated search operators and regulating them in a fixed portion. The occurrences of exploration and exploitation are controlled by algorithm parameters. Thus, the spy algorithm parameters provide good before-running intuition to easier reach the balance between exploration and exploitation. The spy algorithm is first designed to be used in the continuous optimization model. The spy algorithm was compared to the genetic algorithm, improved harmony search, and particle swarm optimization on a set of non-convex functions by aiming at accuracy, the ability to detect many global optimum points, and computation time. The Kruskal-Wallis tests, followed by Games—Howell post hoc comparison tests, were conducted using a. for the comparison. The statistical analysis results show that the spy algorithm outperformed the other algorithms by providing the best accuracy and detecting more global optimum points within less computation time. Furthermore, those results indicate that the spy algorithm is more robust and faster than other algorithms tested. On the other hand, the B-VNS algorithm is a modification of the variable neighborhood search (VNS) algorithm. The benefit of VNS comes from its thorough search while avoiding the local optimum trap by moving to the neighboring point called shaking. The local search after shaking is another benefit of VNS that makes VNS a prominent algorithm. However, the thorough search has the drawback of long computation time. This dissertation introduces a modified neighborhood structure to reduce the computation times. The main idea is to apply the binomial distribution to create the neighboring point. As a result, the neighborhood distance has a random pattern. However, it follows a binomial distribution instead of a strictly monotonic increase like in VNS. The B-VNS is a modification of VNS and is classified as a single solution-based algorithm. The B-VNS is intended to solve combinatorial optimization problems, particularly the quadratic unconstrained binary optimization (QUBO) problems categorized as NP-hard problems. The B-VNS and VNS algorithms were tested on standard QUBO problems from Glover and Beasley, on standard max-cut problems from Helmberg-Rendl, and those proposed by Burer, Monteiro, and Zhang. Finally, Mann-Whitney tests were conducted using a. to compare the performance of the two algorithms statistically. It was shown that the B-VNS and VNS algorithms are able to provide good solutions, but the B-VNS algorithm runs substantially faster. Furthermore, the B-VNS algorithm performed better in all of the max-cut problems regardless of problem size and in QUBO problems with sizes less than The spy algorithms and B-VNS have different designs in the process and the domain of the solved problems. However, considering the benefit of the spy algorithm and B-VNS, their combination has the potential to provide good results. Conceptually, the spy algorithm can be seen as the first step of B-VNS. Conversely, B-VNS can be considered an additional refinement for the spy algorithm.

近年，情報通信技術の進化は著しく，データ主導型社会への転換が進むなか，公共データの活用促進，すなわち「オープンデータ」の動きが世界的に広がっている．わが国でも2012年には「電子行政オープンデータ戦略」が政府決定され，オープンデータが本格的にスタートした．オープンデータは，単なる情報公開にとどまるものではなく，公共データを二次利用可能な形（機械判読に適したデータ形式，無償，再配布可能等）で民間に開放することにより，データがこれまで以上の価値を生み出すことを狙うものである． 災害対策，土木・建築事業，ヘルスケア分野など，様々な分野でオープンデータの活用が始まっており，実際に公共の利益に資する例やビジネスの収益をもたらす例などを，確認することができる．しかし，オープンデータに取り組んでいる地方公共団体は未だ100%には至っていない．また，行政が掲げているオープンデータに取り組む意義・目的のすべてが達成されているとは言い難い状況にある． そこで本論文では，研究の対象主体を地方公共団体に定め，わが国のオープンデータを取り巻く生態系（エコシステム）について仮説を立て，実証実験を行い，地方公共団体のオープンデータ推進を阻む問題点と解決方法を明らかにすることを主たる研究目的とする．そのうえで，オープンデータの付加価値向上の検討を次の目的とする．具体的には，公開されている公共データを情報・ナレッジにまで加工し公表することで，地域社会の課題解決に貢献できるか検討することを目指す． これらの目的を遂行するために，本論文は次の3つのテーマに取り組む．(1)全国の地方公共団体のオープンデータ取り組みの実態を明らかにし，そこに潜む課題を明確にする．(2)わが国のオープンデータの生態系に登場する，データ提供者，サービス利用者，インフラ提供者などのアクター間の関係を包括的に考察し，地方公共団体がオープンデータを推進するための新たなモデルを提案する．(3)地域活性化にかかわる政策の，提言・評価に直接役立つように「データを情報に変換する」という試みを通じて，オープンデータ活用の更なる可能性を論じる． 本論文の主要な成果は以下の通りである．地方公共団体のオープンデータ推進の実態解明では，市区町村レベルで当該取り組みを促進するには自治体間の連携が重要であることを明らかにし，自治体間連携には3つのタイプがあることを示した．次に，総務省が実施したアンケート調査を自治体の人口規模別に分析することにより，市町村レベルで推進が進まない要因を明らかにした．また，既存のホームページによるデータ公開と，新たなオープンデータによるデータ公開が混在する現状を整理し，そこに潜む課題を明確にした．以上の結果を踏まえたうえで，オープンデータ・エコシステムという枠組みで現状をモデル化し，新たに”データ仲介者”という活動主体での取り組み方法を提案した．そして，都道府県が公開している社会指標を研究対象に選択し，山口県庁にて実験を行い，提案するモデルの効果を実証した．最後に，公共データの一歩進んだ活用法として産業連関表を用いた経済波及効果推計法を提案し，IT産業の立地が少ない地方公共団体では経済波及効果の相当規模が域外に漏出してしまうことを明らかにした．これにより，データの持つ価値を高めて，政策評価にも応用できることを示した． 本論文は，以下の8章から成る． 第1章では，序論として研究の背景，目的および構成について記載する． 第2章では，自治体の情報化推進の歴史を概観したうえで，オープンデータについて定義や意義などを整理し，地方公共団体が直面する課題について論じる． 第3章では，上述の3つのテーマ(1)～(3)に対する先行研究について述べ，本論文が目指す点を明示する． 続く第4章から第7章が，本論文の主な研究成果になる．テーマ(1)は第4，5章に，テーマ(2)は第6章に，テーマ(3)は第7章に相当する． 第4章では，都道府県別にその管内の全市区町村のなかでオープンデータをインターネットで提供している市区町村の割合を算出し，訂正調査と組み合わせて分析した結果について述べる．市区町村のオープンデータの促進には，自治体間の連携が重要であることを明らかにし，自治体間の連携に3つのタイプがあることを示した．そのなかで，”都道府県がポータルサイトの公開機能を市区町村に提供し，その機能を利用して管内自治体が自らオープンデータをアップロードするタイプ”が最も有望であることを示した． 第5章では，より深く地方公共団体のオープンデータ推進の現状を解明する．先進自治体にインタビュー調査を実施したうえで，総務省が実施したアンケート調査結果を再分析し，自治体の人口規模の際により，オープンデータの公開状況に生じる違いについて定量的に検証した．その結果，①地方公共団体のオープンデータ推進には当該団体の人口規模が大きく関係していること，②現状では従来からのホームページサイトと，新たなオープンデータサイトが混在していて，「データの重複に伴う問題」が存在すること，の2点を明らかにした． 第6章では，オープンデータ・エコシステムの枠組みを用いて，わが国のオープンデータを取り巻く世界を描出し，新たに”データ仲介者”という活動主体を取り入れたモデルを提案した．従来，行政には専ら”データ提供者”の立場が求められてきたが，”データ仲介者”の立場を主体的に採ることで，少ないリソースでも付加価値を高めたデータを公開できることを示した．このことを山口県庁での社会指標を対象にした実験で検証した． 第7章では，情報・知識への返還を通じて公開データの価値を高め，政策の提言や評価に繋げることが可能であるかの検証を行った．具体的には，産業連関表を用いた「簡便差分法」という手法を提案し，ソフトウェア系IT企業が都市部に偏在する特徴が，地方公共団体のデジタル化投資の経済効果にどのような影響を及ぼすかを分析した．その結果，IT産業の立地が少ない地方公共団体では，経済波及効果の相当規模が域外に漏出してしまうことを明らかにした．この情報は政策評価に繋がる可能性を持つ． 最後に，第8章で，本論文の総括として，各章の成果をまとめ，今後の課題を論じた．

Nutrient pollution is one of our most pervasive, expensive, and challenging environmental problems, according to the United States Environmental Protection Agency (EPA). Phosphorus is one of the nutrients that are essential for the growth of living organisms. However, excessive amounts of nutrients released into the environment by human activities can harm ecosystems and impact human health. In surface waters, phosphorus can contribute to an overgrowth of algae called algal "blooms" that can sicken or kill wildlife and endanger aquatic habitats. Algal blooms consume dissolved oxygen in the water, leaving little or no oxygen for fish and other aquatic organisms. Algal blooms can harm aquatic plants by blocking the sunlight they need to grow. Some algae produce toxins and encourage the growth of bacteria that can make people sick who are swimming or drinking water or eating contaminated fish or shellfish. Phosphorus is often a major limiting nutrient freshwater system. Consequently, many of the wastewater treatment plant discharged into freshwater systems such as lakes, ponds, and rivers have phosphorus discharge limits. In an attempt to prevent harmful environmental effects of excess phosphorus, several techniques have been designed to remove phosphorus from wastewater. These techniques range from adsorption and precipitation to enhanced biological phosphorus removal and constructed wetlands. Biological phosphorus removal (BPR) was first used at a few water resource recovery facilities in the late 1960s. A common element in EBPR implementation is the presence of an anaerobic tank (no nitrate and oxygen) before the aeration tank. In the next aerobic phase, these bacteria can accumulate large amounts of polyphosphate in their cells and phosphorus removal is said to be increased. The group of microorganisms that are largely responsible for P removal are known as the phosphorus accumulating organisms (PAOs). One of the options to remove phosphorus is to utilize bacteria from nature, besides being easy to obtain and inexpensive. The application of bacteria from sediment and seawater was able to reduce phosphorus in wastewater. In this study, for screening salt-tolerant phosphorus accumulating organisms (PAOs) and investigating the P release and uptake of the organisms in saline wastewater. The samples used were sediment and seawater from Yamaguchi Bay, Yamaguchi, Japan. Sediment and seawater added 150 mL of artificial saline wastewater with media (anaerobic media). The samples were then cultured and given feed media every three hours day at 25 °C and shaken at 140 rpm. The hydraulic retention time of the cultivation was 16 h and 8 h under anaerobic and aerobic conditions, respectively. 10 sponges made of polyurethane with dimensions of 2 cm were put in Erlenmeyer flasks and was used as a bio-carrier surface for microorganisms to adhere to. Water was passed over the sponge surface to acclimatize the microorganisms growing outside the sponge as well as within its pores, ensuring sufficient growth surface. The cultivation duration was 112 days. Batch experiments were conducted over 98 days in solutions with a salinity of 3.5% and P concentrations of 1, 5, 10, and 20 mg-P/L. The P-uptake ability of microorganisms increased by increasing P concentration from 1 to 20 mg-P/L. A high P removal percentage with an average of 85% was obtained at 10 mg-P/L after day 56. The uptake and release of P were observed in saline wastewater, signifying that salt-tolerant PAOs could grow in the saline solution. Bacterial screening by isolation and sequence analysis using 16S rRNA demonstrated that two cultivated strains, TR1 and MA3, had high similarity with Bacillus sp. and Thioclava sp. EIOx9, respectively. The colony morphology analysis showed that the colonies of TR1 were rod-shaped, milky-colored, round, shiny-viscous, smooth with a defined margin, while colonies of MA3 were cream-colored with smooth surfaces and raised aspect. The TR1 was gram-stain-positive with approximately 6-10 μm long and 1.2 μm wide cells, and MA3 was gram-stain-negative with about 0.9 μm long and 0.5 μm wide cells. The results demonstrated the involvement of Bacillus sp., and Thioclava sp. in the release and uptake of P, owing to their ability to grow in saline wastewater. Furthermore, Bacillus sp. (TR1) and Thioclava sp. (MA3) were assessed for their abiotic adaptability and phosphorus removal efficiency in saline wastewater. The effects of abiotic factors such as carbon source, pH, temperature, and salinity on bacterial growth were examined through a series of batch experiments. Both bacteria used carbon sources such as glucose, sucrose, and CH3COONa for their growth. The pH study indicated that Bacillus sp. (TR1) preferred the pH range of 6 8 and Thioclava sp. (MA3) preferred the pH range of 6-9. Bacillus sp. favorably multiplied in the temperature range of 25- 40 °C, while 25 35 °C was preferred by Thioclava sp. Salinity range of 0% 10% was favorable for TR1, with optimum growth observed at 3.5% 5%, and Thioclava sp. (MA3) preferred the salinity range of 1% 10% with optimal growth at 4%, but was absent in non-saline water. Bacillus sp. and bacterial combination (TR1 and MA3) showed similar values for phosphorus removal efficiency (100%) at 1.0 mg-P/L total P compared to Thioclava sp. (38.2%). The initial phosphorus concentration of 2.5 mg-P / L showed a slightly higher 72.35% P removal efficiency compared to the individual strains. However, phosphorus removal did not increase, but showed a downward trend with increasing at initial phosphorus. The combination possibly built a synergistic activity between the individual strains to remove phosphorus. The results demonstrated that when used individually, Bacillus sp. showed a reasonably high phosphorus removal ability than Thioclava sp., and exhibited good synergy when used in combination to remove phosphorus from saline wastewater.

　本研究では、小児期（幼児期、学童期、青年期）の生活習慣、遺伝要因と肥満との関連を調査し、肥満予防のための公衆衛生的アプローチを検討した。食物繊維摂取が学童期の子どもの肥満および血圧、血中脂質パラメーターに及ぼす影響を明らかにすること（調査1：10～11歳の横断研究）、FT0遺伝子多型が幼児期から青年期の体格変化に及ぼす影響を明らかにすること（調査2：3歳、10歳、13歳に渡る縦断研究）、さらに、学童期から青年期にかけて身体活動がFT0遺伝子多型と体格変化に及ぼす影響を明らかにすること（調査3：13歳、18歳に渡る縦断研究）、を本研究の目的とした。 　調査1では、学童期の食物繊維摂取は肥満およびコレステロール高値のリスク低減に有効であることが示唆された。 　調査2では、幼児期から学童期にかけてFT0遺伝子の影響が強く表れ、中学生の年代になるとこの影響は逆に減弱し、部活動等が始まるこの時期の身体活動の影響が関連している可能性があることが推測された。 　調査3では、青年期で、身体活動量が多いほどBMIの増加を弱め、FT0遺伝子多型の影響を減弱させた。 　本論文の構成は5章からなる。 第1章では、緒言として、研究の背景と本研究の目的を述べる。 第2章では、食物繊維摂取が学童期の子どもの肥満および血圧、血中脂質パラメーターに及ぼす影響を検討した。 第3章では、FT0遺伝子多型が幼児期から青年期の体格変化に及ぼす影響を検討した。 第4章では、身体活動がFT0遺伝子多型と体格変化に及ぼす影響について検討した。 第5章では、結言として、本研究のまとめと今後の研究の方向性、今後の展望を述べた。

Phosphorus is an indispensable nutrient to sustain the daily life of all living things on Earth. However, the over-enrichment of the aquatic ecosystem with phosphorus leads to eutrophication, which is still a global environmental problem. More stringent regulations have been put in place for the limit of phosphorus discharge to address this problem and resulted in the removal of phosphorus removal becomes exceptionally crucial. Furthermore, phosphorus deposits are a non-renewable resource and forecasted to deplete until 2170, given the current usage and global population growth. Thus, the removal of phosphorus coupled with the recovery and reuse of phosphorus offer the best strategies to meet the future phosphorus demand. Accordingly, adsorption represents a fascinating separation technique for phosphate from water because of the possibility of phosphorus recovery. Moreover, this approach has many advantages, such as efficient, easy operating conditions, low sludge production, and the possibility of regenerating the adsorbent. Numerous attractive low-cost adsorbents have been studied for phosphate removal, one of which is layered double hydroxides (LDH). Unfortunately, a high phosphate adsorption capacity of LDH can generally be achieved by calcination, which increases the preparation cost of LDH. In this study, LDH is functionalized with amorphous zirconium (hydr)oxide to obtain enhanced adsorption capacity and eliminate the high-temperature requirement during the synthesis process. Although different treatment techniques have been developed to eliminate phosphorus contamination, including for wastewater treatment, treated water often fails to meet quality regulations. Amorphous zirconium (hydr)oxide/MgFe layered double hydroxides composites (am-Zr/MgFe-LDH) with different molar ratios (Zr/Fe = 1.5 2) were prepared in two-stage synthesis by the combination of coprecipitation and hydrothermal methods. The synthesis of the composite could eliminate the requirement of high-temperature calcination in the LDH for phosphate adsorption. Moreover, the phosphate adsorption ability of the composite was higher than that of the individual LDH and amorphous zirconium (hydr)oxide. The presence of amorphous zirconium (hydr)oxide increased the phosphate adsorption ability of composite at low pH. The adsorption capacity was increased by decreasing the pH and increasing the temperature (from 290 to 324 K). The bicarbonate (HCO3 ) was the most competitive anion for phosphate adsorption. The pseudo-secondorder model provided the best description of the kinetic adsorption data. Furthermore, the adsorbed phosphate was easily desorbed by 1 N and reused 2 N of NaOH solutions. The results suggest that the am-Zr/MgFe-LDH composite is a promising material for phosphate removal and recovery from wastewater. A Fixed-bed column has been considered an industrially feasible technique for phosphate removal from water. Besides the adsorption capacity, the effectiveness of an adsorbent is also determined by its reusability efficiency. In this study, phosphate removal by a synthesized am-Zr/MgFe-LDH in a fixed-bed column system was examined. The results showed that the increased bed height and phosphate concentration, and reduced flow rate, pH, and adsorbent particle size were found to increase the column adsorption capacity. The optimum adsorption capacity of 25.15 mg-P g^{-1} was obtained at pH 4. The coexistence of seawater ions had a positive effect on the phosphate adsorption capacity of the composite. Nearly complete phosphate desorption, with a desorption efficiency of 91.7%, could be effectively achieved by 0.1 N NaOH for an hour. Moreover, the initial adsorption capacity was maintained at approximately 83% even after eight adsorption-desorption cycles, indicating that the composite is economically feasible. The am-Zr/MgFe-LDH, with its high adsorption capacity and superior reusability, has the potential to be utilized as an adsorbent for phosphorus removal in practical wastewater treatment. The possible adsorption mechanisms of phosphate by am-Zr/MgFe-LDH were investigated via X-ray diffraction (XRD), Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and pH at the point of zero charge (pHPZC) analyses. It was suggested that the high phosphate adsorption capacity of the composite involves three main adsorption mechanisms, which are the electrostatic attraction, inner-sphere complexation, and anion exchange, where the amorphous zirconium (hydr)oxide on the surface of the layered double hydroxides likely increased the number of active binding sites and surface area for adsorption. This study provides insights into the design of am-Zr/MgFe- LDH for phosphorus removal and recovery in a practical system.

Chromatography is considered as a key operation in the downstream process (DSP) of biopharmaceuticals, including proteins. Therapeutic proteins such as monoclonal antibodies (mAbs) with high economic values in the global market require immediate innovation in the purification step to adapt to the increased throughput from upstream. Authorities have also initiated changes toward a more modernized pharmaceutical manufacturing platform which is agile and flexible without extensive oversight. Instead of the conventional batch operation and empirical models, the design and application of in silico modeling and simulation for integrated multi-column processes to improve their performance in capture chromatography steps have been explored in the dissertation. Due to the fact that mechanistic models can reveal adsorption and mass transfer behaviors better in the chromatography compared to statistical models, mechanistic frameworks were applied in the study. Ion-exchange and protein A chromatography, the main categories of therapeutic protein chromatography were examined. With an example of oligonucleotides, the mass transfer phenomenon of biomolecules in different types of ion-exchange resins was explored by mechanistic models. The results demonstrate the effectiveness of modeling approaches to understand the chromatography process of biopharmaceuticals. By focusing on the DSP of mAbs, multi-column continuous chromatography was examined with IgG samples. The study covered the repeating batch to 4-column settings in the continuous periodic counter-current (PCC) chromatography, with development in modeling and simulation tools for process quantification and evaluation. Process performances including productivity, capacity utilization, and buffer consumption were investigated by simulations with the aim to increase productivities and lower buffer consumptions, which are the main bottleneck in the current DSP. The critical operation parameter, breakthrough percent (BT%) for column switching in PCC processes, requires the information from binding capacity, mass transfer, and non-loading operations. To obtain the optimal BT% under synchronized conditions, numerical solvers developed from mechanistic models were employed. It was found that over 20% improvement in buffer consumption and resin utilization can be observed in PCC processes while the same productivity as batch operation is maintained. Furthermore, regressive relations were developed for predictions of process performances and BT% based on the findings from PCC simulations. With high coherence in R2 over 0.95, the linear regression function can act as an accelerated method in the PCC process design. Finally, a new strategy of linear flow-velocity gradient (LFG) in the loading step was explored as a supplement to increase process efficiency. The method controls the total column capacity and the loaded amount as functions of time. Based on the relationship between the dynamic binding capacity and residence time, the gradient time of LFG was obtained. The optimal flow velocities and time gradients were examined by scanning through the range of applicable residence times. A case study of the 4-column PCC process is presented. By integrating a linear decreasing flow gradient in the PCC loading operation, the productivity has 1.4 times enhancement along with a 13% reduction in the cost of resin per amount of processed mAbs compared to constant flows. Undoubtedly, the next generation of DSP platform technology is directed toward continuous and integrated systems. Regarding the advantages in process performances and regulation perspectives, continuous manufacturing can advance development and manufacturing while assuring the product quality. The evolution in modeling and simulation enables faster development of in silico process prediction and evaluation. With the support from models, process design and optimization in chromatography can rise to the challenge.