Abstract: The lack of blood-brain barrier (BBB) penetrating ability has hindered the delivery of many therapeutic agents for tauopathy therapeutic treatment. A circular bifunctional aptamer reported here has been able to enhance the in vivo BBB penetration for improved therapy. The circular aptamer includes one transferrin receptor (TfR) aptamer to facilitate TfR-aptamer recognition-induced transcytosis across BBB endothelial cells, and one Tau protein aptamer selected to inhibit Tau phosphorylation and other tauopathy-related pathological events in the brain. This bispecific construct exhibits strong specificity towards Tau and enhanced plasma stability in comparison to linear Tau aptamer. In vivo administration of circular Tau-TfR aptamer results in a rapid uptake into relevant brain regions after crossing the BBB, such as hippocampus and cortex.

Abstract: Exemplary aspects disclosed herein include detecting a repetitive pattern in an instruction pipeline of a processor to reduce repeated fetching. The processor includes a pattern record circuit configured to receive information in a data stream (e.g., instructions or consumed data) in the instruction pipeline. The pattern record circuit includes a first in, first out (FIFO) table circuit that contains an input record column and plurality of additional adjacent record columns. As new data occurs in the data stream, the data record circuit is configured to sequentially record next incoming data from the data stream into a next input entry of an input record column and then shift previously recorded data into adjacent entries of adjacent record columns. The distance between the input record column and the additional record column that has matching data is the distance in the data stream between a reoccurrence of data in the data stream.