Artificial Intelligence
Kanazawa University research: Shedding light on how tissues grow with sharply defined structures
KANAZAWA, Japan, Oct. 3, 2024 /PRNewswire/ — Researchers at Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, demonstrate how morphogens combined with cell adhesion can generate tissue domains with a sharp boundary in an in vitro model system.
Figure 1 https://nanolsi.kanazawa-u.ac.jp/wp/wp-content/uploads/Toda_Fig.-1.jpgCaption Figure 1: How does the morphogen gradient regulate multicellular patterning?
Recent advances that have enabled the growth of tissue cultures into organoids and embryoids have heightened interest as to how tissue growth is controlled during the natural processes of embryo development. It is known that the diffusion of signaling molecules called morphogens directs patterned tissue growth but what has been harder to understand is how the gradient of morphogens from this diffusion can lead to sharply defined domains in the resulting tissue (Fig. 1). Now Satoshi Toda at Kanazawa University NanoLSI (currently Osaka University, Institute for Protein Research), alongside Kosuke Mizuno at NanoLSI and Tsuyoshi Hirashima at the National University of Singapore, demonstrate a simple model system – SYnthetic Morphogen system for Pattern Logic Exploration using 3D spheroids (SYMPLE3D) – that sheds light on the process.
Various previous studies have looked at the role of morphogens and cell adhesion during tissue growth separately. However, the researchers noted a couple of recent studies indicating how a morphogen involved in neural tube patterning controls expression of a family of adhesion proteins called cadherins to form sharply defined structures. Prompted by these insights, they devised their model system to investigate the interplay between morphogens and cadherins. They highlight how in vivo morphogens induce numerous changes in cellular properties simultaneously, making it hard to disentangle what is going on. For this reason, as they highlight in the discussion of their report, “SYMPLE3D provides a new synthetic biology approach for mechanistically studying tissue patterning and engineering organoid structures.”
SYMPLE3D uses two types of cells – one, the GFP secretors, which secrete GFP and express P-cadherin forming what they describe as “GFP-secreting organizer spheroids”. The other is a GFP receiver cell, initially engineered to express a synthetic receptor called “synNotch” that recognizes GFP and induces mCherry reporter – “imC cells” (Fig. 2A).
The first stage looked at the result of co-culturing the GFP secretors and receiver cells. They found that although the imC cells did capture the secreted GFP resulting in a GFP gradient, the resulting gradient contained ectopically active cells – expression of the high-level mCherry reporter in an inappropriate position of the gradient (Fig. 2B, upper panel). To deal with the issue of ectopically active cells, Mizuno and Toda engineered GFP receiver cells to induce mCherry-fused E-cadherin, a cell adhesion molecule. To their surprise, a uniformly activated tissue domain with sharp boundary emerged instead of a gradient between the secretor and receiver cells (Fig. 2B, lower panel).
Figure 2: https://nanolsi.kanazawa-u.ac.jp/wp/wp-content/uploads/Toda_Fig.-2.jpgCaption Figure 2. Tissue domain formation through the coupling of morphogen signals and cell adhesion. (A) SYnthetic Morphogen system for Pattern Logic Exploration using 3D spheroids (SYMPLE3D). (B) mCherry (upper panel) or Ecad-mCherry (lower panel) was induced in response to the GFP gradient.
The sharp boundary was also robust to changes in growth conditions. Since the addition of a single factor, E-cadherin, caused a significant change in the pattern, they then focused on the mechanism of the pattern formation process with a combination of molecular gradient and E-cadherin in their model system.
By monitoring the real time process of tissue growth, they were able to identify activated GFP receiver cells engineered to induce mCherry-fused E-cadherin were initially scattered but aggregated over the course of time. Ectopically active cells were then gradually absorbed into this active domain resulting in a sharp cut off between the mCherry positive and negative domains. They also note “an intriguing aspect” of their synthetic tissue domain, in that across the active domain the distribution of induced E-cadherin-mCherry was uniformly high, whereas GFP was distributed with a gradient. Here, they revealed a key feature of E-cadherin for the synthetic tissue domain formation. They analyzed the behavior of cells that express various levels of E-cadherin in response to different amounts of GFP and found that the behavior was the same whether the cells induced low or high levels of E-cadherin. Furthermore, they showed that cells that induced more than a certain amount of E-cadherin were able to mix with each other and form a single cell population, regardless of the expression level. Therefore, the mixing of cells that induced different levels of E-cadherin within the GFP gradient allowed the cells to receive GFP uniformly and thus the expression level of E-cadherin became evenly high in the synthetic tissue domain (Fig. 3). A simple mathematical model, developed by Hirashima, based on cell movement governed by differential adhesion energy supported their experimental observations. “Our findings suggest the possibility of programming a new tissue domain with sharp boundaries in organoids by combining synthetic morphogens with cell adhesion control,” they conclude in their report.
Figure 3: https://nanolsi.kanazawa-u.ac.jp/wp/wp-content/uploads/Toda_Fig.-3.jpgCaption Figure 3. The pattern formation mechanism where morphogen signals and cadherin expression cooperate to generate tissue domains with a sharp boundary.
Note about the contributions of Kosuke Mizuno to research at the NanoLSI
Kosuke Mizuno, a second-year doctoral student in the Nano Life Science Program, has made notable contributions to NanoLSI research. He was awarded the NanoLSI Transdisciplinary Research Grant for FY2023 and FY2024.
Glossary
Morphogen
A signaling molecule that controls cell fate decision dependently on its local concentration to regulate morphogenesis. Morphogens are secreted from source cells, diffuse within tissues and form a concentration gradient that works as positional information for cell differentiation. Representative morphogens include Wnt, BMP, Shh, and retinoic acid.
Cadherins
Cadherins are a family of transmembrane proteins that facilitate cell to cell adhesion. Mizuno, Hirashima and Toda use E-cadherin and P-cadherin in the current study, which belong to the classical cadherin family. Cadherins primarily bind to each other via their homophilic extracellular domains. However, cadherins also have an intracellular domain, which binds to adaptor proteins connected to actin cytoskeletons and contributes to tissue compaction and cell sorting.
Synthetic Notch receptor (synNotch)
Notch is a signal transduction receptor. When the extracellular domain of Notch receptor binds to its ligand Delta, Notch transmembrane region is cleaved, leading to the translocation of Notch intracellular domain into the nucleus to regulate the expression of target genes. The synNotch receptor is a modified version of Notch receptor, in which the extracellular domain of Notch is replaced by an antibody or nanobody and the intracellular domain by an artificial transcription factor. Using synNotch receptors, researchers can design what ligand molecule cells recognize and what target genes cells express in response, which enables manipulation of cell-cell communications.
Reference
Kosuke Mizuno, Tsuyoshi Hirashima, Satoshi Toda. Robust tissue pattern formation by coupling morphogen signal and cell adhesion EMBO Reports. 2024. DOI：10.1038/s44319-024-00261-z URL： https://www.embopress.org/doi/full/10.1038/s44319-024-00261-z
Funding
This research was supported by the World Premier International Research Center Initiative (WPI), MEXT, Japan, Japan Science and Technology Agency (JST) PRESTO (JPMJPR2147), Grant-in-Aid for Scientific Research (20K15828, 21H05291, 21H05290), Japan Agency for Medical Research and Development (AMED) (22bm0704048h0003), Senri Life Science Foundation, Kato Memorial Bioscience Foundation, Kao Foundation, Yoshida Scholarship Foundation, and the Mechanobiology Institute, National University of Singapore.
Contact
Fujiko Imanaga (Ms) Project Planning and Outreach NanoLSI Administration Office, Nano Life Science Institute (WPI-NanoLSI) Kanazawa University Kakuma-machi, Kanazawa 920-1192, Japan Email: [email protected] Tel: +81 (76) 234-4555
About Nano Life Science Institute (WPI-NanoLSI), Kanazawa University
Understanding nanoscale mechanisms of life phenomena by exploring “uncharted nano-realms”.
Cells are the basic units of almost all life forms. We are developing nanoprobe technologies that allow direct imaging, analysis, and manipulation of the behavior and dynamics of important macromolecules in living organisms, such as proteins and nucleic acids, at the surface and interior of cells. We aim at acquiring a fundamental understanding of the various life phenomena at the nanoscale.
https://nanolsi.kanazawa-u.ac.jp/en/
About the World Premier International Research Center Initiative (WPI)
The WPI program was launched in 2007 by Japan’s Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS).
See the latest research news from the centers at the WPI News Portal: https://www.eurekalert.org/newsportal/WPI
Main WPI program site: www.jsps.go.jp/english/e-toplevel
About Kanazawa University
As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities.
The University is located on the coast of the Sea of Japan in Kanazawa – a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students including 600 from overseas.
http://www.kanazawa-u.ac.jp/en/
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Agora Launches Conversational AI SDK, Integrated with OpenAI’s Realtime API to Power the Evolution of Natural, Voice-Driven AI Experiences
SANTA CLARA, Calif., Oct. 3, 2024 /PRNewswire/ — Agora, Inc. (NASDAQ: API), a pioneer and leading platform for real-time engagement APIs, today announced the launch of its revolutionary Conversational AI SDK, integrated with OpenAI’s Realtime API to allow developers to seamlessly bring engaging, voice-driven AI experiences to any app. This integration lets developers build conversational AI for a vast range of use cases and provide users with a more natural way to interact with AI than ever before.
“Real-time conversational AI is the next step in helping consumers and organizations across the world realize the benefits of this seismic and revolutionary technology,” said Tony Zhao, CEO and Co-Founder of Agora. “With OpenAI, our Conversational AI SDK will allow developers everywhere to increase interactivity in their apps by implementing natural voice interaction with the conversational intelligence of OpenAI, thanks to Agora’s robust real-time audio streaming capabilities.”
The Conversational AI SDK leverages Agora’s intelligent routing and ultra-low latency real-time network – which powers 60 billion minutes of real-time interaction per month in over 200 countries and regions globally – to enable human-like voice interactions with OpenAI via the OpenAI Realtime API. The SDK incorporates AI echo cancellation and background noise suppression to deliver accurate voice processing in any environment, making it easy for developers to provide reliable connections with OpenAI’s GPT models.
“By integrating lifelike, interactive AI learning assistants into our platform, we can enhance personalized skill assessments, improve the learning experience for developers, optimize online testing, and create new opportunities to expand our skill assessment and educational services globally,” said Samuel Lim, CEO & Founder of Agora customer Grepp.
The new integration will allow developers to quickly build robust AI voice agents for use cases including 24/7 customer support, concierge services, health and wellness, education and language learning, gaming, voice interfaces and many more.
“Agora’s Conversational AI SDK will make it easy for us to integrate real-time voice interaction with AI into our IoT products,” said Yun Zhang, CEO & Co-founder of Wyze, an emerging Home Intelligence platform with scalable IoT devices that is also an Agora customer. “Agora’s network is a game changer, with the ultra-low latency response time necessary for truly natural voice interaction with AI-powered smart devices.”
“The integration with OpenAI will unleash a wave of creativity and utility in the AI space unlike anything we have seen to date,” concluded Zhao. “Whether it’s wellness coaching in the healthcare space, a 24/7 customer support agent, or a language tutoring app that can help students practice their speaking skills, our Conversational AI SDK and OpenAI’s Realtime API will allow developers to imagine and build apps that would have been inconceivable only a few years ago. It will also help end users leverage AI in their daily lives in entirely new ways – and Agora is thrilled to integrate with OpenAI to make it all possible.”
For more info on Agora’s Conversational AI SDK for OpenAI, check out the webpage: https://www.agora.io/en/products/agora-openai-conversational-ai-sdk/
About Agora
Headquartered in Santa Clara, California, Agora is a pioneer and global leader in Real-Time Engagement Platform-as-a-Service (PaaS), providing developers with simple, flexible, and powerful application programming interfaces, or APIs, to embed real-time voice, video, interactive live-streaming, chat, whiteboard, and artificial intelligence capabilities into their applications.
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Artificial Intelligence
Kao Data Starts Work on the Construction of its £350m, Greater Manchester Data Centre
Greater Manchester Mayor, Andy Burnham, visits the construction site of Kao Data’s new 40MW data centre, set to play a key role in his GM digital strategy over the next decade.The industrial-scale, 25,900sqm data centre will house some of the UK’s most advanced computing technologies, including artificial intelligence (AI) and cloud workloads.Designed to be one of the world’s most energy-efficient facilities and powered by 100% certified renewable energy, the data centre will set new standards in the city for sustainability.STOCKPORT, England, Oct. 3, 2024 /PRNewswire/ — Kao Data, the specialist developer and operator of data centres engineered for AI and advanced computing, has today announced work has commenced on the construction of its new £350 million data centre in Stockport, Greater Manchester.
The news comes as data centres are designated Critical National Infrastructure (CNI) by the UK Government in the first move of its kind since 2015.
Greater Manchester Mayor Andy Burnham and the Leader of Stockport Council, Cllr Mark Hunter, were among those present as work began to demolish existing buildings on the ex-industrial site in preparation for the new data centre, which is expected to be powering customers’ workloads by 2026.
The state-of-the-art facility will further cement Manchester’s growing reputation as a major hub for UK digital infrastructure and technology innovation, and ties into the GMCA’s Greater Manchester Digital Blueprint by extending the region’s world-class digital infrastructure.
Upon completion, the data centre will deliver unrivalled computing capabilities to regional and international organisations, providing them with one of Europe’s most advanced and sustainable hosting environments, powered by 100% certified renewable energy.
The new data centre is also expected to bring numerous high-net-worth employment opportunities to the area, creating both direct and indirect jobs across construction, engineering, and operations, while attracting further tech professionals to the region.
Once operational this facility provides the vital capacity needed for tech businesses to scale and grow, supporting more jobs in the digital sector.
Andy Burnham said: “As we continue our mission to ensure world-class digital infrastructure for the region, this new data centre will play a pivotal part in our fast-growing and diverse technology ecosystem, reinforcing our position as a global leader in AI and data centre capacity.”
“This data centre can also raise aspirations and opportunities for young people, providing a window on the GM economy that they’ve never had before,” he continued. Kao Data’s plans to engage with schools and colleges and support technical career pathways for local students through the Greater Manchester Baccalaureate is exciting, and I’m looking forward to seeing those plans become reality.”
Doug Loewe, CEO, Kao Data, said: “Beginning the development stage of our new data centre marks an important milestone, not only for Kao Data, but for technology in Stockport and Greater Manchester. The city region is becoming an increasingly strategic location for digital infrastructure investment, and our new facility – the largest and most sustainable in the north of England – further reinforces Greater Manchester’s position as a digital and economic powerhouse.”
Cllr Mark Hunter said: “It’s a fantastic opportunity for Stockport to attract businesses like Kao Data to come and be based in the borough, with all the extra job opportunities and support for growing our local economy further that comes with them.
“It’s also a testament to all of the good work and investment in the borough that the Council has led on – with good support from Andy Burnham as GM Mayor – that digital and tech businesses recognise the potential of Stockport as a key location for their growth and further success.”
By 2026, Greater Manchester is expected to emerge as one of the UK and Europe’s largest computing and technology hubs, benefitting from a strategic location that includes access to cutting-edge connectivity, an industrialised power grid, a talented, tech-savvy workforce and well-established AI Start-up and research communities.
Kao Data’s facility is set to be a cornerstone of this transformation, helping businesses across the region stay competitive on the global stage and attract the world’s most pioneering tech players to the North West.
For more information about Kao Data’s Greater Manchester data centre, visit the website.
About Kao Data
Kao Data leads the industry, pioneering the development and operation of UK and European data centres engineered for AI and advanced computing. With hyperscale-inspired facilities east and west of London, and northern England’s largest data centre planned for Greater Manchester, we are home to technology’s most demanding computing infrastructure.
Its award-winning, NVIDIA DGX-Ready certified data centres are designed, engineered, and operated by one of the industry’s most respected teams. Together, this provides colocation customers deploying mission-critical AI, enterprise, and cloud workloads with a secure, scalable, and sustainable compute environment, backed by a guarantee of 100% uptime.
Kao Data’s data centre portfolio includes more than 160 MW of IT load, either currently operational, under development or planned – all of which is under-pinned by the highest energy efficiency, sustainability and ESG credentials.
Backed by leading international investors, and with several pioneering ‘industry firsts’ to our name, Kao Data represents the future in industrial scale, high-capacity data centres for AI and the next generation of compute.
Kaodata.com
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Artificial Intelligence
Commercial HVAC System Shipments Valued at US$354 Billion in 2030 Driven by Innovations in Cooling, Energy Efficiency, and Sustainability
Building codes, energy regulations, and rising operating costs are encouraging building developers to upgrade existing HVAC infrastructure to Smart HVAC equipment
NEW YORK, Oct. 3, 2024 /PRNewswire/ — Building operations and their hardware components are undergoing a wave of digitalization by implementing smart technologies that enable convenience, comfort control, energy efficiency, and operational cost savings. Pressures to comply with sustainability regulations and demand for energy efficiency encourage building owners and engineers to develop optimized Heating, Ventilation, and Air Conditioning (HVAC) strategies to reduce operational costs. According to global technology intelligence firm ABI Research, the current commercial HVAC hardware shipments market is valued at US$161 billion and will grow to US$354 billion in 2030, at an advancing CAGR of 11.9%. This includes packaged systems & rooftop units, conventional systems, Variable Refrigerant Flow Systems (VRF), and multi-split system types.
Traditional HVAC systems have a binary function of ‘On & Off’. Smart HVAC systems have different modes which condition the air based on multiple factors such as ambient temperature, occupancy, equipment scheduling, and energy consumption. “Smart HVAC systems go beyond basic cooling and heating functions by bridging the connected and unconnected through intelligent climate control (temperature, air quality, and humidity tracking), remote management, proactive, predictive maintenance, and energy optimization. Currently, over 75% of the HVAC systems are hard-wired, as awareness grows over the forecast period by 2030, adoption of wireless connected Smart HVAC systems will reach over 55%,” explains Rithika Thomas, Senior Analyst for Sustainable Technologies at ABI Research.
Building codes and energy utilization regulations globally stress the need for efficient use of HVAC equipment, low-impact/sustainable refrigerant, and optimal set points to reduce energy costs. Energy Performance of Buildings Regulations (EPBD), F-Gas Regulations, the Health and Safety at Work Act 1974, the Control of Legionella Bacteria Regulations 2014, and Indoor Air Quality (IAQ) Regulations are a few edicts shaping the HVAC landscape with a focus on refrigerant type & use, maintenance, environmental impact, and a healthy workplace.
Bosch Group’s recent acquisition of Johnson Controls Residential and Light Commercial HVAC business has cemented its market share in the HVAC market. Established brands like Haier Electronics, Honeywell International, LG Electronics, Mitsubishi Electric Corporation, Panasonic, Midea Group, and Samsung Electronics, to name a few, are strengthening their offerings powered by Artificial Intelligence (AI), to cater to high energy efficiency HVAC systems with low-frequency noise, efficient water use, smart control features, and enhanced cooling capabilities. SMEs digitizing building operations and Building Automation System (BAS) providers like ALE, CIM, SensMax, and Sensgreen are partnering with established market players and commercial developers to prototype, manufacture, test, and deploy smart HVAC solutions in commercial buildings.
HVACs contribute between 38% – 70% of a conventional commercial building’s energy consumption. “Maximizing energy efficiency in HVAC systems for commercial buildings is crucial to creating energy-efficient, sustainable, and comfortable built environment. Smart HVAC empowers occupants to control the temperature of a space on a granular level from dedicated devices, such as a digital dashboard or phone, to achieve thermal comfort. Upskilling of building operators, technicians, and installers on new digital and smart HVAC capabilities is critical to the success and implementation of connected HVAC systems. The smarter era of HVAC will drive connected living to new heights through comfort, convenience, efficiency, and savings,” Thomas concludes.
These findings are from ABI Research’s HVAC Systems & Hardware in Commercial Buildings market data report. This report is part of the company’s Smart Buildings research service, which includes research, data, and ABI Insights. Market Data spreadsheets comprise deep data, market share analysis, and highly segmented, service-specific forecasts to provide detailed insight into where opportunities lie.
About ABI Research
ABI Research is a global technology intelligence firm uniquely positioned at the intersection of technology solution providers and end-market companies. We serve as the bridge that seamlessly connects these two segments by providing exclusive research and expert guidance to drive successful technology implementations and deliver strategies proven to attract and retain customers.
ABI Research是一家全球性的技术情报公司，拥有得天独厚的优势，充当终端市场公司和技术解决方案提供商之间的桥梁，通过提供独家研究和专业性指导，推动成功的技术实施和提供经证明可吸引和留住客户的战略，无缝连接这两大主体。
For more information about ABI Research’s services, contact us at +1.516.624.2500 in the Americas, +44.203.326.0140 in Europe, +65.6592.0290 in Asia-Pacific, or visit www.abiresearch.com.
Contact Info:
Global Deborah PetraraTel: [email protected]
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