Human cerebrospinal fluid monoclonal LGI1 autoantibodies increase neuronal excitability

OBJECTIVE: Leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common antibody-mediatedencephalopathy, but insight into the intrathecal B-cell autoimmune response, including clonal relationships, isotype dis-tribution, frequency, and pathogenic effects of single LGI1 antibodies, has remained limited. METHODS: We cloned, expressed, and tested antibodies from 90 antibody-secreting cells (ASCs) and B cells from thecerebrospinalfluid (CSF) of several patients with LGI1 encephalitis. RESULTS: Eighty-four percent of the ASCs and 21% of the memory B cells encoded LGI1-reactive antibodies, whereasreactivities to other brain epitopes were rare. All LGI1 antibodies were of IgG1, IgG2, or IgG4 isotype and had under-gone affinity maturation. Seven of the overall 26 LGI1 antibodies efficiently blocked the interaction of LGI1 with itsreceptor ADAM22 in vitro, and their mean LGI1 signal on mouse brain sections was weak compared to the remaining,non–ADAM22-competing antibodies. Nevertheless, both types of LGI1 antibodies increased the intrinsic cellular excit-ability and glutamatergic synaptic transmission of hippocampal CA3 neurons in slice cultures. Interpretation: Our data show that the patients’intrathecal B-cell autoimmune response is dominated by LGI1 anti-bodies and that LGI1 antibodies alone are sufficient to promote neuronal excitability, a basis of seizure generation.Fundamental differences in target specificity and antibody hypermutations compared to the CSF autoantibody reper-toire in N-methyl-D-aspartate receptor encephalitis underline the clinical concept that autoimmune encephalitides arevery distinct entities

Does Blockchain for 3D Printing Offer Opportunities for Business Model Innovation?

Blockchain combined with 3D printing offers businesses untapped opportunities. Blockchain can help businesses overcome intellectual property and data security barriers, allowing them to take advantage of emerging 3D printing business models. Specifically, blockchain can facilitate local manufacturing and may lay the groundwork for new business models like industrial design marketplaces and shared factories. Businesses could also improve their value proposition by offering additional services around a printed part, improving value delivery, and offering less costly and more customized products that involve fewer risks. Blockchain could transform the way firms create, deliver, and capture value in 3D printing ecosystems

Barriers to the Adoption of Blockchain Technology in Business Supply Chains: A Total Interpretive Structural Modelling (TISM) approach

Blockchain is an emerging technology with a wide array of potential applications. This technology, which underpins cryptocurrency, provides an immutable, decentralised, and transparent distributed database of digital assets for use by firms in supply chains. However, not all firms are appropriately suited to adopt blockchain in the existing supply chain primarily due to their lack of knowledge on the benefits of this technology. Using Total Interpretive Structural Modelling (TISM) and Cross-Impact Matrix Multiplication Applied to Classification (MICMAC), this paper identifies the adoption barriers, examines the interrelationships between them to the adoption of blockchain technology, which has the potential to revolutionise supply chains. The TISM technique supports developing a contextual relationship based structural model to identify the influential barriers. MICMAC classifies the barriers in blockchain adoption based on their strength and dependence. The results of this research indicate that the lack of business awareness and familiarity with blockchain technology on what it can deliver for future supply chains, are the most influential barriers that impede blockchain adoption. These barriers hinder and impact businesses decision to establish a blockchain-enabled supply chain and that other barriers act as secondary and linked variables in the adoption process