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1. Differential gene expression between callosal and ipsilateral projection neurons in the monkey dorsolateral prefrontal and posterior parietal cortices

   https://doi.org/10.1093/cercor/bhac157  

   Arion, Dominique; Enwright, John F; Gonzalez-Burgos, Guillermo; Lewis, David A (April 2022, Cerebral Cortex)

   Abstract Reciprocal connections between primate dorsolateral prefrontal (DLPFC) and posterior parietal (PPC) cortices, furnished by subsets of layer 3 pyramidal neurons (PNs), contribute to cognitive processes including working memory (WM). A different subset of layer 3 PNs in each region projects to the homotopic region of the contralateral hemisphere. These ipsilateral (IP) and callosal (CP) projections, respectively, appear to be essential for the maintenance and transfer of information during WM. To determine if IP and CP layer 3 PNs in each region differ in their transcriptomes, fluorescent retrograde tracers were used to label IP and CP layer 3 PNs in the DLPFC and PPC from macaque monkeys. Retrogradely-labeled PNs were captured by laser microdissection and analyzed by RNAseq. Numerous differentially expressed genes (DEGs) were detected between IP and CP neurons in each region and the functional pathways containing many of these DEGs were shared across regions. However, DLPFC and PPC displayed opposite patterns of DEG enrichment between IP and CP neurons. Cross-region analyses indicated that the cortical area targeted by IP or CP layer 3 PNs was a strong correlate of their transcriptome profile. These findings suggest that the transcriptomes of layer 3 PNs reflect regional, projection type and target region specificity. 

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2. A Blockchain Platform for Protecting Intellectual Property: Implications for Additive Manufacturing

   Esmaeilian, Behzad; Deka, Angshuman; Behdad, Sara (August 2019, the ASME 2019 International Design Engineering Technical Conferences & Computers and Information in Engineering Conference, IDETC/CIE, Aug 18-21, 2019, Anaheim, CA.)

   Prior studies have already predicted that enforcement of IP on the additive manufacturing industry will not be successful due to the widespread use of file-sharing technologies, similar to the entertainment and music industry. This paper discusses the capabilities of Blockchain technology for protecting IP in the design and manufacturing area. A conceptual framework for a digital platform is defined in this paper and further, a survey study of engineering design and manufacturing students has been conducted to identify the main motivation behind developing these platforms and the types of features that should be included in Blockchain-based IP platforms for asset protection, particularly for product design. In addition, respondents provided their opinions about the type of industry that might be affected more by the threat of counterfeiting products and the role of Blockchain-based IP systems on the growth and development of innovation. 

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3. Connecting the Hosts: Street-Level IP Geolocation with Graph Neural Networks

   https://doi.org/10.1145/3534678.3539049  

   Wang, Zhiyuan; Zhou, Fan; Zeng, Wenxuan; Trajcevski, Goce; Xiao, Chunjing; Wang, Yong; Chen, Kai (August 2022, The 28th ACM SIGKDD Conference on Knowledge Discovery and Data Mining)

   Pinpointing the geographic location of an IP address is important for a range of location-aware applications spanning from targeted advertising to fraud prevention. The majority of traditional measurement-based and recent learning-based methods either focus on the efficient employment of topology or utilize data mining to find clues of the target IP in publicly available sources. Motivated by the limitations in existing works, we propose a novel framework named GraphGeo, which provides a complete processing methodology for street-level IP geolocation with the application of graph neural networks. It incorporates IP hosts knowledge and kinds of neighborhood relationships into the graph to infer spatial topology for high-quality geolocation prediction. We explicitly consider and alleviate the negative impact of uncertainty caused by network jitter and congestion, which are pervasive in complicated network environments. Extensive evaluations across three large-scale real-world datasets demonstrate that GraphGeo significantly reduces the geolocation errors compared to the state-of-the-art methods. Moreover, the proposed framework has been deployed on the web platform as an online service for 6 months. 

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4. CODEIPPROMPT: intellectual property infringement assessment of code language models

   Yu, Zhiyuan; Wu, Yuhao; Zhang, Ning; Wang, Chenguang; Vorobeychik, Yevgeniy; Xiao, Chaowei (July 2023, Proceedings of the 40th International Conference on Machine Learning)

   Recent advances in large language models (LMs) have facilitated their ability to synthesize programming code. However, they have also raised concerns about intellectual property (IP) rights violations. Despite the significance of this issue, it has been relatively less explored. In this paper, we aim to bridge the gap by presenting CODEIPPROMPT, a platform for automatic evaluation of the extent to which code language models may reproduce licensed programs. It comprises two key components: prompts constructed from a licensed code database to elicit LMs to generate IP-violating code, and a measurement tool to evaluate the extent of IP violation of code LMs. We conducted an extensive evaluation of existing open-source code LMs and commercial products, and revealed the prevalence of IP violations in all these models. We further identified that the root cause is the substantial proportion of training corpus subject to restrictive licenses, resulting from both intentional inclusion and inconsistent license practice in the real world. To address this issue, we also explored potential mitigation strategies, including fine-tuning and dynamic token filtering. Our study provides a testbed for evaluating the IP violation issues of the existing code generation platforms and stresses the need for a better mitigation strategy. 

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5. Administration of FVIII-Expressing Human Placental Cells to Juvenile Sheep Yields Multi- Organ Engraftment, Therapeutic Plasma FVIII Levels and Alter Immune Signaling Pathways to Evade FVIII Inhibitor Induction

   Trevisan, Brady; Rodriguez, Martin; Dizon, Jacqueline; George, Sunil; Shields, Jordan; Lankford, Shannon; Combs, Rebessa; Owen, John; Atala, Anthony; Doering, Christopher; et al (December 2021, ASH)

   Administration of FVIII-Expressing Human Placental Cells to Juvenile Sheep Yields Multi-Organ Engraftment, Therapeutic Plasma FVIII Levels and Alter Immune Signaling Pathways to Evade FVIII Inhibitor Induction 63rd ASH Annual Meeting and Exposition, December 11-14, 2021, Georgia World Congress Center, Atlanta, GA Program: Oral and Poster Abstracts Session: 801. Gene Therapies: Poster III Hematology Disease Topics & Pathways: Bleeding and Clotting, Biological, Translational Research, Hemophilia, Genetic Disorders, Immune Mechanism, Diseases, Gene Therapy, Therapies, Adverse Events, Biological Processes, Transplantation Monday, December 13, 2021, 6:00 PM-8:00 PM We have previously reported that normal juvenile sheep that received weekly intravenous (IV) infusions of human (n=3) or an expression/secretion-optimized, bioengineered human/porcine hybrid (ET3) FVIII protein (n=3) for 5 weeks (20 IU/kg) developed anti-FVIII inhibitory antibodies (10-116 BU, and IgG titers of 1:20–1:245) by week 3 of infusion. By contrast, the IV infusion, or IP administration, of human placental mesenchymal cells (PLC) transduced with a lentiviral vector encoding a myeloid codon-optimized ET3 transgene (PLC-mcoET3) to produce high levels of ET3 protein (4.9-6IU/10^6 cells/24h) enabled the delivery of FVIII without eliciting antibodies, despite using PLC-mcoET3 doses that provided ~20-60 IU/kg ET3 each 24h to mirror the amount of FVIII protein infused. In addition, we showed that the route of PLC-mcoET3 administration (IP vs IV) did not impact the resultant plasma FVIII levels, with animals in these two groups exhibiting mean increases in FVIII activity (quantified by aPTT) of 30.9% and 34.2%, respectively, at week 15 post-treatment. Here, we investigated whether the sites and levels of PLC-mcoET3 engraftment were dependent upon the route of administration and performed s sheep-specific multiplexed transcriptomic analysis (NanoString) to define the immune signaling pathways that thwarted FVIII/ET3 protein immune response when ET3 was delivered through PLC. Tissue samples were collected from various organs at euthanasia and RT-qPCR performed using primers specific to the mcoET3 transgene, to the human housekeeping transcript GAPDH, and to sheep GAPDH, to quantify PLC-mcoET3 tissue engraftment, and normalize the results. RT-qPCR demonstrated PLC-mcoET3 engrafted, in both IP and IV groups, in all the organs evaluated (liver, lung, lymph nodes, thymus, and spleen). Animals that received PLC-mcoET3 via the IP route displayed higher overall levels of engraftment than their IV counterparts. The spleen was the preferential organ of engraftment for both IP and IV groups (IP:2.41±1.97%; IV: 0.64±0.54%). The IP group exhibited significantly higher engraftment in the left lobe of the liver (IP: 1.36±0.35%; IV: 0.041±0.022%), which was confirmed by immunohisto-chemistry (IHC) with an antibody to the human nuclear antigen Ku80 and ImageJ analysis (IP:5.24±3.36%; IV: 0±0). Of note is that the IP route resulted in higher levels of engraftment in the thymus, while IV infusion yielded higher levels of PLC-mcoET3 in lymph nodes. Analysis of H&E-stained tissues demonstrated they were devoid of any abnormal histologic changes and exhibited no evidence of hyperplasia or neoplasia, supporting the safety of the cell platform, irrespective of the route of administration. To date, NanoString analysis of PBMC collected at day 0, week 1, and week 5 post-infusion demonstrated that animals who received FVIII protein had upregulation of UBA5 and BATF, genes involved in antigen processing and Th17 signaling pathways, respectively. Although both IV and IP recipients of PLC-mcoET3 also had an increase in BATF, the IV group exhibited upregulation of BTLA, a gene involved in immune-tolerance, and downregulation of NOTCH and DDL1, involved in T cell differentiation, as well as MAPK12 and PLCG1, genes involved in proinflammatory cytokine regulation and T signaling within the Th17 signature. In IP recipients, BTLA, NOTCH, and DLL1 were all downregulated. Since ET3-reactive Th1 cells were not present in any of the treated animals, it is possible that the Th17 cells are responsible for the inhibitory antibodies seen in the juvenile sheep treated with FVIII/ET3 protein, while in animals receiving PLC-mcoET3, downregulation of genes involved in T cell differentiation and proinflammatory cytokine signaling keeps the immune system in check to avoid an immune response. Disclosures: Doering: Expression Therapeutics: Divested equity in a private or publicly-traded company in the past 24 months. Spencer: Expression Therapeutics: Divested equity in a private or publicly-traded company in the past 24 months. 

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