Innovative Platform Research Articles

3D‐Printed Tissue‐Specific Nanospike‐Based Adhesive Materials for Time‐Regulated Synergistic Tumor Therapy and Tissue Regeneration In Vivo

AbstractThe growing concerns regarding cancer recurrence, unpredictable bone deficiencies, and postoperative bacterial infections subsequent to the surgical removal of bone tumors have highlighted the need for multifaceted bone scaffolds that afford tumor therapy, bacterial therapy, and effective vascularized bone reconstruction. However, challenging trilemma has emerged in the realm of bone scaffolds regarding the balance between achieving appropriate mechanical strength, ensuring biocompatibility, and optimizing a degradation rate that aligns with bone‐regenerative rate. Considering these challenges, innovative theragenerative platform is developed by utilizing 3D printing‐based nanospikes for the first time. This platform comprises tissue‐specific nanospiked hydroxyapatite decorated with magnesium (nMg) and adhesive DNA (aDNA). The incorporation of nMg within polylactic acid (PLA) matrix confers photothermal capabilities and helps to modulate mechanical and degradation properties and improve the biocompatibility of theragenerative platform. Simultaneously, the immobilized aDNA contributed to the enhancement of vascularized bone healing. These 3D‐printed tissue‐adhesive theragenerative platforms exhibit superior mechanical properties and offer controlled degradability. Moreover, they enable the eradication of bacteria and osteosarcoma through hyperthermia and promote angiogenesis and osteogenesis, both in vitro and in vivo. This groundbreaking approach is poised to pave the way for the fabrication and design of novel implantable biomaterials that integrate therapeutic and regenerative functions.

Innovative Adaptive Multiscale 3D Simulation Platform for the Yellow River Using Sphere Geodesic Octree Grid Techniques

Earth system simulation technology is fundamental for ecological protection and high-quality development in the Yellow River Basin. To address the lack of a Yellow River simulation platform, this study proposes an adaptive multiscale true 3D crust simulation platform using the Sphere Geodesic Octree Grid (SGOG). Twelve models in four categories were designed: single fine-scale models, geomorphic zone-based models, and models using both top-down and bottom-up approaches. The models were evaluated based on terrain feature representation and computational efficiency. The results show that single fine-scale models preserve detailed terrain features but are computationally intensive. They are suitable for the precise simulation of surface processes. Top-down and bottom-up models balance terrain detail and efficiency, and are thereby widely applicable. Geomorphic zone-based models provide detailed focal area representation and higher computational efficiency, being more targeted. Various methods offer flexible scale transformations, each with its own strengths, allowing researchers to select a method according to practical application needs. Consequently, this research demonstrates that spherical discrete grids offer reliable support for constructing basin simulation platforms, providing new technological and scientific insights for the Yellow River Basin’s ecological protection and development.

A Comprehensive Study of UPI and Modern Digital Financial Transactions

Our project researches into the world of digital finance, focusing on the Unified Payments Interface (UPI) and modern financial transactions. As technology advances, traditional financial methods are evolving, making way for innovative platforms like UPI. Our study aims to thoroughly understand UPI and its implications for today's financial landscape. Through careful research, we explore the fundamental workings of UPI, its structure, and its role in facilitating smooth transactions between individuals and groups. We also investigate the security measures embedded within UPI to ensure the safety of user data and transactions. Moreover, our project researches into the broader realm of digital financial transactions, encompassing various digital payment platforms. We analyze the advantages and challenges posed by these platforms and their impact on financial accessibility and inclusion. By blending theoretical knowledge with practical examples, our study provides valuable insights into UPI and modern digital transactions. It aims to contribute to a better understanding of how these technologies are shaping the future of financial services and driving economic progress.

Conceptual Design and Structural Performance Analysis of an Innovative Deep-Sea Aquaculture Platform

This paper proposes a conceptual design of an innovative deep-sea aquaculture platform that integrates a steel structural framework and high-density polyethylene (HDPE) floats. It aims to overcome the limitations of prevailing aquaculture equipment, including inadequate resistance to strong wind and waves, complex technologies, and prohibitively high costs. The design scheme and key parameters of the main platform, the netting system, and the mooring systems are presented. Based on the stochastic design wave method, the characteristic load response scenarios and design wave parameters are determined and analyzed. Strength analysis is conducted to assess the structural performance, vulnerabilities, and overall safety of the platform under various characteristic load conditions. The results indicate that the Von Mises stress levels across different sections of the platform conform to the allowable stress thresholds under various characteristic load conditions. However, the stress levels of the platform are notably higher when subjected to characteristic loads associated with vertical shear, vertical bending moments, and torsion about the horizontal axis, which requires further efforts in the design process to enhance the structural safety of the platform. The proposed design methodology and the presented research results can provide a wide range of references for the design and analysis of deep-sea fisheries aquaculture equipment.

Financial Technology for the Sustainable Development

The Sustainable Development Goals (SDGs) are the critical goals for every country in the world. A stable global financial system is needed these days to satisfy its duty to boost private capital mobilization to achieve sustainable development and steady economic growth. However, several obstacles limiting such financial mobilization have been identified by scholars, practitioners, and standard setters. In recent times digital transformation and advancement, specifically in the finance sector, include a wide range of technological developments, and applications such as blockchain, the Internet of things, big data, and artificial intelligence are promised to enhance performance in the financial sector. The potential of digital applications in the finance sector to resolve critical obstacles in financing for inclusive and sustainable growth becomes evident. Financial inclusion is indisputably one of the most significant processes towards achieving the Sustainable Development Goals and FinTech is one of the best methods for these goals to be accomplished. The Fintech industry in India is rapidly expanding and the purpose of this paper is to discuss issues such as fintech drivers, shortcomings of traditional financial services, and the role of technological advancement. The paper also addresses issues relating to fintech investment and disturbance. Financial technology faces challenges such as investment management, customer management, and regulation. The paper examines the evolution of fintech in the banking sector over time. But as we are aware a country like India lacks proper infrastructure and management and the objectives of banking can’t not be attained easily. All the issues and challenges faced by the government and financial institutions have been discussed in this paper along with the important and different strategies adopted by them. The study is based on secondary data and a literature review. India has surpassed the global fintech adoption rate to promote financial transactions with the help of technology. Demonetisation and implementation of the GST (goods and services tax) have also played a major role in the adoption of financial technologies among the masses. Also, the announcement made by the government in 2017 to decrease the amount of paper currency in circulation has elevated its awareness. Blockchain is another financial technology that is being used in the industry. Out of the total “fintech” technologies, blockchain was developed for finance which is directly connected to financial institutions. The main aim of Blockchain in financial services is decentralization where we do not trust a third party to execute transactions. It includes services such as transferring funds between banks and companies. While trading in capital markets, innovative electronic trading platforms facilitate online trade and real-time transfers. Trading networks allow investors to observe the trading behavior of their peers and expert traders and to follow their investment strategies on currency exchange and capital markets. These platforms require either very little or no knowledge about financial markets. An automated financial advisor provides financial advice or online investment management with moderate minimal human intervention.

Adoption of Fintech for Sustainable Administrative Efficiency of Higher Educational Institutions: Bangladesh Perspective

Fintech solutions offer innovative tools and platforms that streamline financial operations, enhance convenience, and improve efficiency. The purpose of this research is to examine the impact of fintech on administrative efficiency among universities in Bangladesh. To fulfil this purpose, this research assesses the current level of fintech adoption among university students in Bangladesh and seeks to gain insights into students’ perceptions and attitudes towards fintech, particularly in relation to its impact on administrative tasks within their respective universities. Finally, this research identifies the challenges and opportunities associated with the integration of fintech in administrative processes and explores potential strategies to address them effectively. This research used both quantitative and qualitative strategies to achieve these goals. A survey was conducted to collect quantitative data from the university students of Bangladesh. Findings show that the adoption and usage of fintech have a statistically significant positive impact on administrative efficiency, resource allocation and utilisation, enhanced communication, and a sustainable and eco-friendly administrative environment.

Two dimensional alkaline earth metal sensors (2D-AEMS) of fluorescent strontium sulfide nanosheets for neurotransmitter drug detection via photo induced electron transfer (PIET)

A new sensing platform has been introduced that provides a powerful solution for fluorescence-based biosensors using photoluminescent nanosheets (NS) using the novel two dimensional alkaline earth metal sensors (2D-AEMS). We have synthesized two-dimensional (2D) fluorescent strontium sulfide (SrS) NS using deep eutectic solvent (DES) as green solvent media by a hydrothermal method. The resulting product of 2D SrS NS to enhance the fluorescence intensity was achieved successfully followed by probe ultrasonication. The optical properties of SrS NS were studied by UV–visible and photoluminescence (PL) spectroscopy. The 2D SrS NS showed a blueish-green fluorescence optimized at λex320 nm/λem390 nm and a quantum yield of 38.6% was calculated. Under optimal conditions, the fluorescent SrS NS effectively detected noradrenaline (NA) by PIET-based fluorescence quenching and wavelength shifts were observed. Our proposed 2D-AEMS of 2D SrS NS fluorescence intensity was quenched in a wide linear range from 1 to 300 µM, with a limit of detection (LOD = 3*3SD/S) of 0.047 µM. The 2D-AEMS (fluorescent SrS NS) was applied to the determination of NA in human urine samples, with good recovery ranging from 98.7-100.08%. Also, the SrS NS fluorescence quenching mechanism in the detection of NA was investigated by zeta potential analysis, UV analysis, and dynamic light scattering (DLS). Our proposed 2D SrS NS fluorescence nanomaterials stand as an innovative platform for generating fluorescence sensors, with extensive potential applications in medical, biological, and life science fields, designed to replace traditional dye fluorescence in the near future.

Label-free electrochemical aptasensor for the detection of HepG2 hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) is the most common liver malignancy and is characterized by increasing incidence and high mortality rates. Current methods for the screening and diagnosis of HCC exhibit inherent limitations, highlighting the ever-growing need for the development of new methods for the early diagnosis of HCC. The aim of this work was to develop a novel electrochemical aptasensor for the detection of HepG2 cells, a type of circulating tumor cells that can be used as biomarkers for the early detection of HCC. A carbon screen-printed electrode was functionalized with a composite suspension containing graphene oxide, chitosan, and polyaniline nanoparticles to increase the electrode surface and provide anchoring sites for the HepG2 cell-specific aptamer. The aptamer was immobilized on the surface of the functionalized electrode using multipulse amperometry, an innovative technique that significantly reduces the time required for aptamer immobilization. The innovative platform was successfully employed for the first time for the amplification-free detection of HepG2 cells in a linear range from 10 to 200,000 cells/mL, with a limit of detection of 10 cells/mL. The platform demonstrated high selectivity and stability and was successfully used for the detection of HepG2 cells in spiked human serum samples with excellent recoveries.Graphical abstract

The Evolution of Dong Small Songs and Cultural Change in Chinese Folk Music

This study investigates the cultural evolution and contemporary significance of Dong's small songs within the realm of Chinese folk music. Through ethnographic fieldwork, interviews, archival research, and thematic analysis, the historical roots and socio-cultural dynamics of Dong's small songs are explored. The literature review delves into the cultural significance, historical evolution, preservation efforts, and challenges faced by Dong small songs, highlighting their role in reflecting regional identities and cultural change. The material and methods section outlines the qualitative research approach, including participant observation, semi-structured interviews, and archival data collection. The research results illuminate the multifaceted nature of Dong small songs, showcasing their adaptability, transmission processes, and contemporary expressions. Suggestions for future research emphasize the need for continued preservation efforts, innovative presentation platforms, and collaborative initiatives to ensure the sustainability and appreciation of Dong's small songs in the context of evolving cultural landscapes.

Platform control and multi-realized platform benefits: a meta-analysis

PurposePlatform owners need to encourage yet control complementors in ways that generate benefits. Retaining too much control can restrict innovation and knowledge flows; giving up too much control can lead to poor quality and platform instability. Studies provide mixed findings that make it difficult to draw generalizable conclusions. We aim to provide a more accurate understanding of the link between platform control and platform benefits.Design/methodology/approachWe conducted a meta-analysis of empirical research in this area.FindingsAccess-based control positively influences realization benefits, but it does not appear to affect creation benefits. Authority-based control does not appear to affect creation or realization benefits. Control is positively linked to benefits on transaction platforms but not on innovation platforms. Platform control is positively related to platform benefits in studies that use objective measures and in studies that measure control from the complementor’s perspective. However, the relationship between control and benefits is uncertain in studies that use perceptual measures and in studies that measure control from the owner’s perspective.Research limitations/implicationsTighter restrictions on who can join the platform can lead to greater use of platform innovations. Platform control is also an effective driver of benefits on transaction platforms. Researchers should carefully think through the manner in which they measure platform control and platform benefits. Our study is limited by a small sample size, four moderators and a set of empirical-only studies.Originality/valueOur findings can guide future research and help practitioners better understand when platform control is related to platform benefits.

Counter Measures to Combat Money Laundering in the New Digital Age

Money Laundering has been a significant concern for governments, law enforcement agencies, and financial institutions worldwide. With the advancement of technology, money laundering techniques have evolved in the digital age, presenting new challenges for authorities and financial institutions. Criminals leverage innovative digital platforms, cryptocurrencies, and virtual assets to launder illicit funds while maintaining anonymity and complexity in their transactions. In this article, we examine the money laundering techniques in the digital age and the challenges posed by these techniques and the implications for the global financial system. Furthermore, the article explores the role of regulatory frameworks, technological solutions, and international cooperation in mitigating the risks associated with digital money laundering. We also explore the countermeasures implemented to detect and prevent these illicit activities. Enhanced Know Your Customer (KYC) regulations, robust transaction monitoring systems, international collaboration, and innovative technologies are among the critical measures to combat digital money laundering.

Collaboration of corporates with coworking spaces: different pathways to develop innovation capabilities

Although academia has witnessed increasing interest in coworking spaces over the past decade, the corporate perspective on utilizing such spaces has not been thoroughly studied. This paper investigates corporate goals, activities, and outcomes of corporate–coworking collaboration by examining 11 different cases in which corporates engage in coworking spaces. We find that, based on their goals, corporates choose different collaboration pathways to enhance their innovation capabilities. We call these pathways explorer, startup hunter, implementer, and transformer. Coworking spaces play an essential role by hosting and orchestrating key open innovation actors, resources, and activities such as scanning, scouting, community building, co‐development, and learning. They are emerging as an open innovation platform that can trigger sensing, seizing, and transforming capabilities of corporates. Our study contributes to the innovation management and the coworking space literature and offers practical implications for both corporates and coworking spaces.

Agricultural Innovation and Food Security in Sub-Saharan Africa in Nigeria

Purpose: The aim of the study was to analyze the agricultural innovation and food security in Sub-Saharan Africa in Nigeria. Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries. Findings: In Nigeria, agricultural innovation is vital for improving food security. Research suggests that adopting innovative farming methods and technologies can boost productivity, resilience to climate change, and livelihoods for smallholder farmers. Overcoming challenges like limited access to finance and inadequate infrastructure is essential to fully harnessing the benefits of agricultural innovation for food security in Nigeria. Unique Contribution to Theory, Practice and Policy: Diffusion of innovations theory, social capital theory & political economy theory may be used to anchor future studies on agricultural innovation and food security in Sub-Saharan Africa in Nigeria. Promote farmer-centered innovation platforms - establishing can facilitate knowledge sharing, collaboration, and co-creation of agricultural innovations. Adequate funding for research institutions, agricultural universities, and extension agencies is essential to conduct applied research, develop appropriate technologies, and provide technical assistance to farmers.

Poly(ferrocenylsilane)-Based Redox-Active Artificial Organelles for Biomimetic Cascade Reactions.

Artificial organelles serve as functional counterparts to natural organelles, which are primarily employed to artificially replicate, restore, or enhance cellular functions. While most artificial organelles exhibit basic functions, we diverge from this norm by utilizing poly(ferrocenylmethylethylthiocarboxypropylsilane) microcapsules (PFC MCs) to construct multifunctional artificial organelles through water/oil interfacial self-assembly. Within these PFC MCs, enzymatic cascades are induced through active molecular exchange across the membrane to mimic the functions of enzymes in mitochondria. We harness the inherent redox properties of the PFC polymer, which forms the membrane, to facilitate in-situ redox reactions similar to those supported by the inner membrane of natural mitochondria. Subsequent studies have demonstrated the interaction between PFC MCs and living cell including extended lifespans within various cell types. We anticipate that functional PFC MCs have the potential to serve as innovative platforms for organelle mimics capable of executing specific cellular functions.

Reducing teacher stress and burnout and enhancing self-efficacy through technology-supported small-group instruction

Teaching is a challenging profession, and teachers experience stress due to the difficulties associated with shifting educational policies, disengaged or dissatisfied parents, and the behavioral, emotional, and academic needs of diverse students. This stress can lead to burnout, which often results in departure from K-12 education system. These stressors can also reduce teachers’ sense of self-efficacy, i.e., their perceived ability to accomplish tasks and overcome challenges. These elevated levels of stress and burnout and reductions in self-efficacy negatively impact student outcomes. In this study, we evaluated the potential for cooperative learning (CL) to reduce stress and burnout and enhance teacher self-efficacy. To aid in the implementation of CL and reduce the burden on teachers, we used an innovative software platform (PeerLearning.net). Data were from a cluster randomized trial encompassing 12 middle and high schools (N = 111 teachers, 62.2 % female, 86.5 % White). We found that teachers in intervention schools (i.e., schools given training and access to PeerLearning.net) reported reduced levels of stress and beneficial effects on self-efficacy (i.e., higher levels of Student Engagement and Instructional Strategies) and burnout (i.e., reductions in Emotional Exhaustion and higher levels of Personal Accomplishment) compared to teachers in control schools that conducted business as usual. We found no significant differences in Classroom Management (an element of self-efficacy) and Depersonalization (an element of burnout). These results suggest that CL, implemented with PeerLearning.net, can have some beneficial effects on teacher well-being.

Circular RNA-based therapy provides sustained and robust neuroprotection for retinal ganglion cells

Ocular neurodegenerative diseases like glaucoma lead to progressive retinal ganglion cell (RGC) loss, causing irreversible vision impairment. Neuroprotection is needed to preserve RGCs across debilitating conditions. Nerve growth factor (NGF) protein therapy shows efficacy but struggles with limited bioavailability and a short half-life. Here we explore a novel approach to address this deficiency by utilizing circular RNA (circRNA)-based therapy. We show that circRNAs exhibit an exceptional capacity for prolonged protein expression and circRNA-expressed NGF protects cells from glucose deprivation. In a mouse optic nerve crush model, lipid nanoparticle-formulated circNGF administered intravitreally protects RGCs and axons from injury-induced degeneration. It also significantly outperforms NGF protein therapy without detectable retinal toxicity. Furthermore, single-cell transcriptomics revealed LNP-circNGF’s multifaceted therapeutic effects, enhancing genes related to visual perception while reducing trauma-associated changes. This study signifies the promise of circRNA-based therapies for treating ocular neurodegenerative diseases and provides an innovative intervention platform for other ocular diseases.

Do multilevel agricultural innovation platforms support inclusive innovation? Lessons learned from a case study in the Ethiopian highlands

ABSTRACT To facilitate smallholder farmers' inclusion within agricultural change processes, agricultural innovation platforms are increasingly being used. Such platforms, which seek to facilitate farmer interactions with diverse actors, are associated with the concept of inclusive innovation. Despite the rhetoric of IPs as inclusive structures, questions persist regarding farmers’ inclusion in decision-making within IPs. This research, based on a livestock innovation case study in the Ethiopian Highlands, examines the role of multilevel IPs in supporting inclusive innovation. Qualitative data collection, timeline analysis of the innovation process and thematic analysis were employed. Results reveal varying levels of farmer inclusion across different phases of the innovation process and IP operational levels. While successful farmer inclusion was apparent in the diagnosis and decentralized learning innovation processes, maintaining inclusivity during the latter phases of the innovation process was difficult, and negatively impacted on farmer-centric outcomes. Decentralized resources, decision-making and reflexive monitoring emerge as crucial in improving smallholder farmers’ inclusion and addressing institutional biases inherent in the technology-push approaches to innovation, especially during farmers’ selection processes that continued to favour better-off or well-connected ‘model’ farmers.

Competitive electrochemical aptasensor for high sensitivity detection of liver cancer marker GP73 based on rGO-Fc-PANi nanocomposites

Golgi protein 73 (GP73) is a novel tumor marker in the early diagnosis and prognosis of hepatocellular carcinoma (HCC). Herein, a competitive electrochemical aptasensor for detecting GP73 was constructed using reduced graphene oxide-ferrocene-polyaniline nanocomposite (rGO-Fc-PANi) as the biosensing platform. The rGO-Fc-PANi had larger specific surface area, excellent conductivity and outstanding electroactive performance, which served as nanocarrier for GP73 aptamer (GP73Apt) binding and as redox nanoprobe for record electrical signal. Then, a complementary chain (cDNA) was fixed to the electrode by hybridization with GP73Apt. When GP73 was present, a competitive process happened among cDNA, GP73Apt and GP73, formed the GP73-GP73Apt stable chemical structure and made cDNA detach from the sensing electrode, resulting in enhancement of electrical signal. The difference in the corresponding peak current before and after the competition can be used to indicate the quantitative of GP73. Under optimal conditions, the DPV current response showed a good log-linear relationship with GP73 concentrations (0.001 ∼ 100.0 ng/mL) with a detection limit of 0.15 pg/mL (S/N = 3). It was successfully used for GP73 detection in human serum with RSDs ranging from 1.08 % to 6.96 %. Therefore, the aptasensor could provide an innovative technology platform and hold a great potential in clinical application.

Unlocking Interactive Learning: Building a Robust Quiz Portal with MERN Stack Technology"

Online learning has become increasingly popular in the digital era, necessitating innovative platforms to effectively engage students. This research outlines the development and implementation of an interactive quiz portal utilizing the MERN (MongoDB, Express.js, React.js, and Node.js) stack to enhance learning outcomes. The portal features a user-friendly interface for easy navigation and access to a diverse range of quizzes on various subjects. To ensure scalability, performance, and real-time interactions, Node.js handles backend operations, React.js manages dynamic interfaces, Express.js is used for server-side development, and MongoDB stores data. The portal includes instant feedback mechanisms, gamification elements, and personalized user profiles to enhance user motivation and involvement. Furthermore, adaptive algorithms are employed to adjust quiz content based on user proficiency levels. This paper presents the design, development, and implementation of an online test platform using the MERN (MongoDB, Express, React, and Node.js) stack. The portal functions as an all-inclusive platform for administering tests, assessments, and learning evaluations in an online setting. The portal provides smooth integration of frontend and backend activities, guaranteeing strong performance and user interaction, by utilizing the adaptability and scalability of the MERN stack. The portal enables quick development and deployment cycles with the help of MongoDB's document-based data storage, Express.js's effective middleware and routing, React.js's dynamic UI components, and Node.js's event-driven architecture. To improve user experience and learning results, features including interactive feedback mechanisms, real-time performance monitoring, quiz design and administration, and user authentication are easily integrated.

Developing an innovative 3D printing platform for production of personalised medicines in a hospital for the OPERA clinical trial

Breast cancer is the most frequently diagnosed cancer in women worldwide, and non-adherence to adjuvant hormonotherapy can negatively impact cancer recurrence and relapse. Non-adherence is associated with side effects of hormonotherapy. Pharmacological strategies to mitigate the side effects include coadministration of antidepressants, however patients remain non-adherent. The aim of this work was to develop medicines containing both hormonotherapy, tamoxifen (20 mg), along with anti-depressants, either venlafaxine (37.5 or 75 mg) or duloxetine (30 or 60 mg), to assess the acceptability and efficacy of this personalised approach for mitigating tamoxifen side effects in a clinical trial. A major criterion for the developed medicines was the production rate, specified at minimum 200 dosage units per hour to produce more than 40,000 units required for the clinical trial. A novel capsule filling approach enabled by the pharmaceutical 3D printer M3DIMAKER 2 was developed for this purpose. Firstly, semi-solid extrusion 3D printing enabled the filling of tamoxifen pharma-ink prepared according to French compounding regulation, followed by filling of commercial venlafaxine or duloxetine pellets enabled by the development of an innovative pellet dispensing printhead. The medicines were successfully developed and produced in the clinical pharmacy department of the cancer hospital Gustave Roussy, located in Paris, France. The developed medicines satisfied quality and production rate requirements and were stable for storage up to one year to cover the duration of the trial. This work demonstrates the feasibility of developing and producing combined tamoxifen medicines in a hospital setting through a pharmaceutical 3D printer to enable a clinical trial with a high medicines production rate requirement.