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Kanazawa University research: Experiments provide insights into the molecular mechanism for memory and learning

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KANAZAWA, Japan, July 3, 2023 /PRNewswire/ — Researchers at Kanazawa University report in Science Advances high-speed atomic force microscopy experiments that show the structural and chemical changes in an enzyme thought to play a vital role in modulating the strength of neural connections.
Synapses connect neurons allowing the transmission of signals around the neural network. The strength of these connections varies – for instance strengthening or weakening depending on the signals received and how. This synaptic ‘plasticity’ underlies learning and memory, and the Ca2+/calmodulin-dependent protein kinase II (CaMKII) is known to play a key role. Previous studies have provided some clues to the mechanisms of CaMKII protein activity in these functions but no one had seen these proteins in action. Now, Hideji Murakoshi at the Graduate University of Advanced Studies and the National Institute for Physiological Sciences and Mikihiro Shibata at Kanazawa University and their colleagues have used high speed atomic force microscopy (HS-AFM) to observe the structural dynamics of these proteins for the first time, not only in various states but in three different species.
CaMKII is common to a vast range of species from mammals like rats to older, non-mammalian species like the roundworms (C. elegans) and hydra. In particular, certain structural features of the protein are particularly well preserved, including the kinase domain, the regulatory segment that inhibits the activity of the kinase domain and the hub domain. In addition, the protein has binding sites, phosphorylation sites and linker regions; however, the linker region shows a little more variability suggesting that its function and activation mechanisms are more bespoke for the different species.
Previous studies had suggested that the regulatory segment’s inhibition of the kinase domain is released when Ca2+/calmodulin binds to the regulatory segment. The activated kinase domains then phosphorylate each other, activity that persists even after the Ca2+/calmodulin becomes dissociated, which has been ‘hypothesized to be a form of molecular memory’, as the researchers describe in their report.
Murakoshi, Shibata and their colleagues studied the protein using atomic force microscopy, which feels topologies using a nanoscale tip, like a needle reading a vinyl record, raster scanning the image plane to build up a picture of the sample structure. With HS-AFM, these images are collected quickly enough to record movies of how these structures change. The researchers noted various measures of the proteins size and motion – the gyrus of rotation – as well as reactions such as kinase domain oligomerization (that is, where there is a limited level of polymerization to join molecules into chains) and phosphorylation – the addition of a phosphoryl group (PO3), which can activate enzymes like kinase.
They found that the kinase domain was quite mobile, although this decreased with Ca2+/calmodulin binding. The researchers explain this in terms of the binding stabilizing the protein into a particular helical structure called an α helix. They also note that the binding causes the protein to extend 3nm from the hub assembly, which they suggest may be what dissociates the regulatory segment from the active site in the kinase domain. The mobility then increases again with phosphorylation, which the researchers attribute to the protein losing some of the order of the helical structure.
Of the three species investigated – the rat, roundworm and hydra – Murakoshi, Shibata and their colleagues found that the kinase domain only oligomerized in the rat. In addition, in the rat, the protein was more resilient to phosphatase, which removes phosphate groups (PO4) from proteins.
“In conclusion,” they report, “Our findings provide a basis for a deeper understanding of the molecular mechanisms of CaMKIIα activation.”
Related imagehttps://onl.tw/nmZ9ei3
CaptionHigh-speed atomic force microscopy image of calmodulin-dependent protein kinase II. This image was taken at 3.3 frames/second. © 2023 Tsujioka, et al., Science Advances.
Glossary
High-speed atomic force microscope
Atomic force microscopy (AFM) ‘feels’ the topography of surfaces by the increase and decrease of surface forces tugging on a nanoscale tip as changes in surface height change the distance between the tip and the surface. The tip is mounted on a cantilever so that the tiny changes in the force can be read out by the resulting deflection in the cantilever.
AFM can resolve structures with subnanometre scale resolution. It has particular advantages for biological studies because it does not require conducting substrates or a current, which are requirements for other primary microscopes with comparable resolutions, such as the scanning tunnelling microscope.
For a long time AFM was limited by the time it takes to capture an image of the surface, but this changed when Toshio Ando at Kanazawa University revealed how the tool could be upgraded to high-speed AFM using various modifications to the scanning, deflection detection and other electronic devices, as well as specifications for the cantilever. With high-speed AFM it became possible to capture dynamics at the nanoscale for the first time.
Ca2+/calmodulin-dependent protein kinase II
Protein kinases are enzymes. They use phosphate sourced from ATP to phosphorylate specific amino acids on target proteins, which leads to changes in the protein’s conformation that regulate its biological activity.
Ca2+/calmodulin-dependent protein kinase II (CaMK II) is a serine/threonine specific protein kinase, which means it phosphorylates the OH groups on the serine or threonine amino acid residues. It is modulated by Ca2+/calmodulin where calmodulin is simply an abbreviation for calcium modulated protein. The type two Ca2+/calmodulin-dependent protein kinases are multifunctional and are involved in neurotransmitter secretion, transcription factor regulation, and glycogen metabolism.
Reference
Shotaro Tsujioka, Ayumi Sumino, Yutaro Nagasawa, Takashi Sumikama, Holger Flechsig, Leonardo Puppulin, Takuya Tomita, Yudai Baba, Takahiro Kakuta, Tomoki Ogoshi, Kenichi Umeda, Noriyuki Kodera, Hideji Murakoshi, Mikihiro Shibata. Imaging single CaMKII holoenzymes at work by high-speed atomic force microscopy, Science Advances June 2023.
DOI: 10.1126/sciadv.adh1069
URL: https://www.science.org/doi/10.1126/sciadv.adh1069
ContactHiroe YonedaSenior Specialist in Project Planning and OutreachNanoLSI Administrative OfficeWPI Nano Life Science Institute (WPI-NanoLSI)Kanazawa UniversityKakuma-machi, Kanazawa 920-1192, JapanEmail: [email protected] Tel: +81 (76) 234-4550
About Nano Life Science Institute (WPI-NanoLSI)
https://nanolsi.kanazawa-u.ac.jp/en/ 
Nano Life Science Institute (NanoLSI), Kanazawa University is a research center established in 2017 as part of the World Premier International Research Center Initiative of the Ministry of Education, Culture, Sports, Science and Technology. The objective of this initiative is to form world-tier research centers. NanoLSI combines the foremost knowledge of bio-scanning probe microscopy to establish ‘nano-endoscopic techniques’ to directly image, analyze, and manipulate biomolecules for insights into mechanisms governing life phenomena such as diseases.
About Kanazawa University
http://www.kanazawa-u.ac.jp/e/ 
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.
 
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More than 150,000 money laundering accounts detected in APAC

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Region sees 108% increase in voice scams as fraudsters continue shift to mobile
MELBOURNE, Australia and MUMBAI, India, June 25, 2024 /PRNewswire/ — A new financial crime report out today details how criminal organizations in the APAC region now outsource the laundering of money stolen via scams to international syndicates specializing in this cleaning. BioCatch identified and helped APAC banks shut down more than 150,000 money mule accounts in 2023 and estimates exponentially more such accounts in use across the region.

“Where there are scams, there are mules,” BioCatch Director of Global Fraud Intelligence Tom Peacock said. “Criminal organizations use these mule accounts as intermediate stops between the victim’s bank account and the final account from which they plan to withdraw their stolen money. The mules we’ve identified almost certainly represent a tiny fraction of those actively laundering money in the region, with more cropping up every day. Financial institutions in APAC and around the world must do more to identify these mules, hamper their ability to open new accounts, and identify those legitimate accounts money launderers succeed in turning from good to bad.”
In this latest edition of its Digital Banking Fraud Trends in APAC report, BioCatch – which identifies and prevents fraud and financial crime in real time by analyzing as many as 3,000 different physical behavior patterns (mouse movements and typing speed, for example) and cognitive signals (hesitation, segmented typing, etc.) in search of anomalies – points to mobile malware as the greatest threat to banks in Southeast Asia in 2024.
“Whether through SMS-mining or illegal loan apps, we’ve seen an explosion in Android-based malware in the region,” Peacock said. “Malware developers continue to innovate, circumventing bank and Google Play Store defenses to harvest what they need from mobile devices to access digital banking accounts and then transfer away the victim’s funds to a money mule.”
There is reason for hope in fighting fraud in APAC, however. In Australia, the number of reported scam cases grew by 13% in 2023, but scam losses declined by $90 million.
“Nine out of the 10 largest Australian banks employ BioCatch solutions to protect their customers from fraud and financial crime by analyzing the behavior of the user behind every online banking session,” BioCatch APAC Vice President Richard Booth said. “Already in 2024, we see massive progress: Money lost to fraud in the country declined by 48% in the first quarter of this year compared to Q1 of 2023. It’s difficult to reach any conclusion other than that BioCatch has left Australian digital-banking customers far safer from fraud than they were before.”
Other key findings:
No desktop or laptop needed: BioCatch found as much as 70% of all reported frauds in APAC originated from mobile apps in 2023, an increase of 17% from the year before.Scams are everywhere: Across the region, the number of reported voice scams increased by 108% in 2023.Australia bucking all trends: In addition to seeing fraud losses actually decline, the nation also saw fewer fraud cases involving malware or Remote Administration Tools (RATs) in 2023 than it did in 2022.Click here to access BioCatch’s complete 2024 Digital Banking Fraud Trends in APAC report.
About BioCatch:BioCatch stands at the forefront of digital fraud detection, pioneering behavioral biometric intelligence grounded in advanced cognitive science and machine learning. BioCatch analyzes thousands of user interactions to support a digital banking environment where identity, trust, and ease coexist. Today, more than 30 of the world’s largest 100 banks and 196 total financial institutions rely on BioCatch Connect™ to combat fraud, facilitate digital transformation, and grow customer relationships. BioCatch’s Client Innovation Board – an industry-led initiative featuring American Express, Barclays, Citi Ventures, HSBC, and National Australia Bank – collaborates to pioneer creative and innovative ways to leverage customer relationships for fraud prevention. With more than a decade of data analysis, 92 registered patents, and unmatched expertise, BioCatch continues to lead innovation to address future challenges. For more information, please visit www.biocatch.com.
Media contact:Jay [email protected]
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Puyi Fund, Managed by Highest Performances Holdings Inc., Surpasses RMB 24.0 Billion in Assets under Advice, Showing Promising Start to Strategic Transformation

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GUANGZHOU, China, June 25, 2024 /PRNewswire/ — Highest Performances Holdings Inc. (“HPH” or the Group, NASDAQ: HPH), announces that its Puyi Fund’s assets under advice for its asset allocation services reached RMB 24.7 billion as of June 21, 2024, reflecting a remarkable year-on-year growth of 188%. This substantial increase in scale showcases significant growth for the fund.

This accomplishment is primarily attributed to the Puyi Fund’s service philosophy, “long-term commitment to clients and clients’ long-term benefits,” introduced in 2023, as well as the ongoing efforts of the Company in adjusting its product strategy and embracing digital transformation. On one hand, the Company implemented a comprehensive family wealth management account system, redirecting its flagship products towards fixed-income funds and fund portfolios to enhance clients’ perception of wealth acquisition. On the other hand, the Company has elevated its overall service standard through digital transformation, greatly improving the client’s investment experience.
Transforming Product Strategy to Maximize Client Returns
In relation to product strategy transformation, Puyi Fund offers investors a comprehensive solution for managing their family wealth through a scientific approach. This solution guides investors in allocating their investment assets across three types of accounts: Flexible Withdrawal Accounts, Stable Appreciation Accounts, and High-Yield Pursuit Accounts. By considering various market conditions and cycles, investors can make informed decisions on how to distribute their funds among these accounts through a scientific approach for achieving risk mitigation, consistent asset growth, and long-term sustainable investment returns.
Taking into account the prevailing market conditions in China, Puyi Fund advises investors to allocate 25% to 90% of their funds to Stable Appreciation Accounts, depending on their risk tolerance. These accounts primarily involve investing in fixed-income funds, providing investors with consistent and reliable expected returns. By employing the stable appreciation strategy, Puyi Fund aims to restore investors’ confidence in the market, leading to increased trust and recognition. Consequently, Puyi Fund has experienced a period of rapid growth and positive development.
An analysis of data from the Chinese mutual fund market highlights the alignment of Puyi Fund’s client-centric product strategy transformation with market demands. According to Wind data, the market value of the Chinese mutual fund market stood at RMB 25.45 trillion at the end of 2021. By the end of May 2024, this amount grew to RMB 29.09 trillion, representing an increase of RMB 3.64 trillion or 14.30%. The value of equity and hybrid funds, however, experienced a decline from RMB 8.54 trillion to RMB 6.34 trillion, marking a decrease of RMB 2.21 trillion. In contrast, bond funds and money market funds collectively witnessed a significant increase of RMB 5.69 trillion. These market trends suggest that Chinese fund investors are shifting their risk preferences towards lower-risk and higher-certainty assets. Puyi Fund’s strategic transformation is well-positioned to take advantage of this evolving trend.
Enhancing Digital Service Innovation with a Focus on Client Service
In its digital transformation efforts, Puyi Fund places a strong emphasis on “client-centricity” and “service excellence”. By harnessing the power of big data, algorithm mining, and the Sensor Intelligent System, Puyi Fund establishes personalized service scenarios tailored to the unique needs of thousands of individuals. Through meticulous operations that cover the full client lifecycle, Puyi Fund offers full-scope online transactions for both public and private fund clients, establishing a distinctive digital competitive advantage. As of June 2024, the year-to-date client retention rate for fund advisory services stands at 75%, significantly enhancing the likelihood of investment profitability and returns for clients. This success enables clients to truly appreciate the value of advisory services and the time invested in their investments.
Furthermore, Puyi Fund has made continuous advancements in its intelligent client service system, leveraging digital platforms to offer investors comprehensive and efficient services. As of June 2024, the intelligent client service has catered to the needs of approximately 250,000 investors, providing 7*24 services, with a problem resolution rate surpassing 90%. Moreover, Puyi Fund complements intelligent client service with human support, resulting in a client satisfaction rate of 99%. This approach guarantees that investors receive timely and effective assistance whenever required.
Optimizing Trust-Based Communication Channels with Clients
Puyi Fund’s capability to swiftly establish client trust is attributable to its distinctive offline service channels. Unlike other third-party fund sales institutions that heavily rely on online platforms, Puyi Fund provides face-to-face, one-on-one services through offline channels. This approach is especially valuable in navigating complex investment environments, effectively calming investor emotions, enabling them to stay composed and gain a proper understanding of products, ultimately making well-informed investment decisions. Since 2024, Puyi Fund’s research and advisory team has released 28 specialized research reports and organized 19 online client exchanges, along with 35 offline client events, in response to market dynamics and client needs. These initiatives have effectively addressed investors’ concerns and enhanced their confidence.
It is worth mentioning that Puyi Fund’s institutional business has experienced remarkable growth this year, particularly in attracting clients from prominent financial institutions including banks, wealth management subsidiaries, and insurance companies. To cater specifically to institutional investors, Puyi Fund has developed an intelligent over-the-counter fund trading system called “Web-based Institution Master system”. This system provides institutional investors with a wide range of product portfolios, a comprehensive investment research system, and personalized trading experiences. As a result, it comprehensively improves the service quality and efficiency for institutional clients.
As of June 21, Puyi Fund established partnerships with 117 mutual fund companies, including the top 20 fund managers in terms of size, providing access to nearly 11,000 public funds and implementing over 20 customized advisory strategies. In the private fund sector, Puyi Fund has selected over 30 fund managers from the entire market. Of these, 38% manage assets over RMB 10 billion, while 29% manage assets between RMB 5 billion and RMB 10 billion. This selection covers a wide range of mainstream strategy products in the market, catering to the allocation needs of various types of investors.
It is reported that Puyi Fund, an independent third-party fund sales institution holding a fund sales business license issued by the China Securities Regulatory Commission, operates as a subsidiary of Highest Performances Holdings Inc. (NASDAQ: HPH). Embracing the concept of buyer advisor, Puyi Fund is dedicated to delivering comprehensive family financial asset allocation services to individual investors and diversified financial services to institutional investors through its financial technology service platform. With exceptional resource integration capabilities, professional research expertise, and high-quality client service, Puyi Fund strives to cultivate long-term partnerships with clients, catering to their personalized asset allocation needs in various scenarios while assisting a broader range of investors in achieving sustainable long-term returns. As of December 31, 2023, the accumulated assets under Puyi Fund’s allocation advisory services surpassed RMB 75.1 billion, exhibiting a compound annual growth rate of 128.8% from 2015 to 2023.
About Highest Performances Holdings Inc. (NASDAQ: HPH)
HPH was founded in 2010 with the aim of becoming a top provider of smart home and enterprise services. Its mission is to improve the quality of life for families worldwide, focusing on two main driving forces: “technological intelligence” and “capital investments.”HPH has a global strategic perspective and identifies high-quality enterprises with global potential for investment and operations. Its areas of focus include asset allocation, education and study tours, cultural tours, sports events, healthcare and elderly care and family governance.
HPH currently holds controlling interests in two leading financial service providers in China, namely Fanhua Inc., a technology-driven platform, and Fanhua Puyi Fund Distribution Co., Ltd., an independent wealth management service provider.
Highest Performances Holdings Inc., formerly known as Puyi Inc., was renamed on March 13, 2024 to reflect its strategic transformation.

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ID Verify Now Available for Yardi Breeze Premier Clients

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Leading software provider introduces biometric technology as the first step in the resident screening process
SANTA BARBARA, Calif.  , June 25, 2024 /PRNewswire/ — In response to the increase in fraudulent applications in multifamily rentals, Yardi® has launched ID Verify for Yardi Breeze® Premier clients in the United States and Canada. The use of biometrics is emerging as a standard screening practice in North America, as it allows property managers to confirm applicant identities before scheduling a tour.

Employing ID Verify as the initial step in the resident screening process provides Breeze Premier clients with a higher level of fraud prevention. Prospective renters simply upload a selfie and a photo of a government-issued identification document to the cloud. Then ID Verify detects fake IDs and validates real identities, ensuring a secure and reliable screening process. The new technology can also manage resident, visitor and vendor access, enhancing community security.
When paired with ScreeningWorks® Pro in the United States or Yardi® Resident Screening in Canada, property managers centralize resident screening data with their property data. This single source of truth provides multifamily businesses with a deeper understanding of who they’re renting to, ensuring greater confidence and quality in resident selection.
“Rising fraud increases the risks of bad debt,” said Peter Altobelli, vice president and general manager of Yardi Canada Ltd.” However, we’re optimistic that ID Verify will safeguard the future of the multifamily market when implemented as the first step in the resident screening process.”
Book a demo to learn more about ID Verify and how it will benefit your property management business.
About Yardi
Celebrating its 40-year anniversary in 2024, Yardi® develops industry-leading software for all types and sizes of real estate companies across the world. With over 9,000 employees, Yardi is working with our clients to drive significant innovation in the real estate industry. For more information on how Yardi is Energized for Tomorrow, visit yardi.com.
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