CH/π interactions in the crystal structure of class I MHC antigens and their complexes with peptides

The crystal structure of class I major histocompatibility complex antigens (MHC) bound to their specific ligand peptides were analyzed, in the context of the CH/π interaction, with use of a computer program CHPI. A number of short CH/C_sp² distances have been shown at the boundary of the heavy chain and β2 microglobulin. These interactions are conserved between species, human versus murine. A number of contacts shorter than the conventional van der Waals distance have been disclosed between CH hydrogens and aromatic side-chain groups in the MHC/peptide complexes. The CH/π interaction has been suggested to contribute to the specificity in the complex formation of class I MHC.     

Low-threshold,high-resolution,chronically stable intracortical microstimulation by ultraflexible electrodes

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Identification of Human Single-Domain Antibodies against SARS-CoV-2

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Fab-based bispecific antibody formats with robust biophysical properties and biological activity

A myriad of innovative bispecific antibody (BsAb) platforms have been reported. Most require significant protein engineering to be viable from a development and manufacturing perspective. Single-chain variable fragments (scFvs) and diabodies that consist only of antibody variable domains have been used as building blocks for making BsAbs for decades. The drawback with Fv-only moieties is that they lack the native-like interactions with C_H1/C_L domains that make antibody Fab regions stable and soluble. Here, we utilize a redesigned Fab interface to explore 2 novel Fab-based BsAbs platforms. The redesigned Fab interface designs limit heavy and light chain mixing when 2 Fabs are co-expressed simultaneously, thus allowing the use of 2 different Fabs within a BsAb construct without the requirement of one or more scFvs. We describe the stability and activity of a HER2×HER2 IgG-Fab BsAb, and compare its biophysical and activity properties with those of an IgG-scFv that utilizes the variable domains of the same parental antibodies. We also generated an EGFR × CD3 tandem Fab protein with a similar format to a tandem scFv (otherwise known as a bispecific T cell engager or BiTE). We show that the Fab-based BsAbs have superior biophysical properties compared to the scFv-based BsAbs. Additionally, the Fab-based BsAbs do not simply recapitulate the activity of their scFv counterparts, but are shown to possess unique biological activity.     

Bioflavonoid Rescue of Ascorbate at a Membrane Interface

In aqueous solution, ascorbate potently prevents bleaching of cytochrome c on exposure to excess H₂O₂ or t-butyl hydroperoxide. Ascorbate failed to protect cytochrome c in the presence of liposomes of mitochondrial membranelike composition. Like the redox mediator N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), however, the bioflavonoids epicatechin and quercetin restored the protection afforded by ascorbate in the presence of liposomes and gave further protection. The quercetin glycoside, rutin, was much less effective, as was the vitamin E analog Trolox. In the presence of liposomes, quercetin alone was relatively ineffective, but cooperated with ascorbate to extend protection synergistically. The results bear specific implications in antioxidant protection of cytochrome c and in moderation of its hydroperoxidase activities in biological membranes. The data also reveal a situation where ascorbate is without effect except in the presence of a bioflavonoid, and substantiate a possibly vital role for certain bioflavonoids in mediating electron transfer from ascorbate into a hydrophobic environment.     

Low Latency High Bandwidth Message Transfer Mechanisms for a Network Interface Plugged into a Memory Slot

The communication architecture of the DIMMnet-1 network interface based on MEMOnet is described. MEMOnet is a class of a network interface plugged into a memory slot. This paper proposes three message transfer mechanisms named atomic on-the-fly sending (AOTF), block on-the-fly sending (BOTF) and OTF receiving with selective address translation. The DIMMnet-1 prototype will have an ASIC named Martini, two banks of PC133 based SO-DIMM slots and an 8 Gbps full duplex optical link. The software overhead incurred to generate a message is only 1 CPU cycle and the estimated hardware delay is 105 ns using AOTF. The estimated hardware delay for receiving to on chip memory using OTF receiver is 90 ns. The estimated achievable sending bandwidth of DIMMnet-1 using BOTF is 984 MB/s which was observed in our experiments. This bandwidth is 7.4 times higher than the maximum bandwidth of PCI. This high performance is available even when simultaneous sending and receiving are executed on a cheap personal computer with DIMM slots. This paper also discribes the effects of BOTF for a PCI-based NIC.