CMOS-Compatible Memristor for Optoelectronic Neuromorphic Computing.

Optoelectronic memristor is a promising candidate for future light-controllable high-density storage and neuromorphic computing. In this work, light-tunable resistive switching (RS) characteristics are demonstrated in the CMOS process-compatible ITO/HfO2/TiO2/ITO optoelectronic memristor. The device shows an average of 79.24% transmittance under visible light. After electroforming, stable bipolar analog switching, data retention beyond 104 s, and endurance of 106 cycles are realized. An obvious current increase is observed under 405 nm wavelength light irradiation both in high and in low resistance states. The long-term potentiation of synaptic property can be achieved by both electrical and optical stimulation. Moreover, based on the optical potentiation and electrical depression of conductances, the simulated Hopfield neural network (HNN) is trained for learning the 10 × 10 pixels size image. The HNN can be successfully trained to recognize the input image with a training accuracy of 100% in 13 iterations. These results suggest that this optoelectronic memristor has a high potential for neuromorphic application.

Rapid analysis of ketamine with in-house antibody conjugated boronic acid modified silver chip on MALDI-TOF MS measurement.

An antibody conjugated boronic acid modified silver chip (ABAS ship) is fabricated as a simple, rapid, accurate, sensitive and cost-effective sample preparation method for abused drug quantification in human urine. Ketamine, one common abused drug, was applied as proof of concept for ABAS chip with high resolution matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF MS) analysis. The overall testing process required 10 min at part per billion (ppb) sensitivity level, where current drug testing method necessitated several hours with similar sensitivity. The ABAS chip manufacture process started with slide glass by way of silver mirror reaction to form silver conductive glass for further chemical conjugation. Boronic acid functional group was decorated on silver conductive glass through the formation of silver-thiol (Ag-S) bond. Anti-ketamine antibody was covalently conjugated to boronic acid modified silver conductive glass through the formation of cyclic boronate ester between the boronic acid and the cis-diol groups on the glycans of antibody, which maintain the correct orientation to maximally capture its antigen. The resulting ABAS chip were designed to specifically capture ketamine in human urine samples, that could be directly analyzed by addition of MALDI α-Cyano-4-hydroxycinnamic acid (CHCA) matrix solution. The linear dynamic range of concentration in this method was 10-500 ng/mL with coefficient of determination 0.996. The limit of detection (LOD) and limit of quantification (LOQ) were 2.0 and 7.0 ng/mL, respectively. Importantly, the proposed method allows rapid and accurate quantification of ketamine from suspects' urine samples in 10 min and small sample volume of 1 µL was required. The resulting data were consistent with traditional gas chromatography-mass spectrometry (GC-MS) analysis. Our homemade ABAS chip could thus provide a powerful tool not only for forensic science but also for most clinical diagnosis of disease as many expression antibodies for the occurrence of diverse diseases could be simply produced and purchased.

Clinical targeting of HIV capsid protein with a long-acting small molecule.

Oral antiretroviral agents provide life-saving treatments for millions of people living with HIV, and can prevent new infections via pre-exposure prophylaxis1-5. However, some people living with HIV who are heavily treatment-experienced have limited or no treatment options, owing to multidrug resistance6. In addition, suboptimal adherence to oral daily regimens can negatively affect the outcome of treatment-which contributes to virologic failure, resistance generation and viral transmission-as well as of pre-exposure prophylaxis, leading to new infections1,2,4,7-9. Long-acting agents from new antiretroviral classes can provide much-needed treatment options for people living with HIV who are heavily treatment-experienced, and additionally can improve adherence10. Here we describe GS-6207, a small molecule that disrupts the functions of HIV capsid protein and is amenable to long-acting therapy owing to its high potency, low in vivo systemic clearance and slow release kinetics from the subcutaneous injection site. Drawing on X-ray crystallographic information, we designed GS-6207 to bind tightly at a conserved interface between capsid protein monomers, where it interferes with capsid-protein-mediated interactions between proteins that are essential for multiple phases of the viral replication cycle. GS-6207 exhibits antiviral activity at picomolar concentrations against all subtypes of HIV-1 that we tested, and shows high synergy and no cross-resistance with approved antiretroviral drugs. In phase-1 clinical studies, monotherapy with a single subcutaneous dose of GS-6207 (450 mg) resulted in a mean log10-transformed reduction of plasma viral load of 2.2 after 9 days, and showed sustained plasma exposure at antivirally active concentrations for more than 6 months. These results provide clinical validation for therapies that target the functions of HIV capsid protein, and demonstrate the potential of GS-6207 as a long-acting agent to treat or prevent infection with HIV.

Functional label-free assays for characterizing the in vitro mechanism of action of small molecule modulators of capsid assembly.

HIV capsid protein is an important target for antiviral drug design. High-throughput screening campaigns have identified two classes of compounds (PF74 and BI64) that directly target HIV capsid, resulting in antiviral activity against HIV-1 and HIV-2 laboratory strains. Using recombinant proteins, we developed a suite of label-free assays to mechanistically understand how these compounds modulate capsid activity. PF74 preferentially binds to the preassembled hexameric capsid form and prevents disruption of higher-order capsid structures by stabilizing capsid intersubunit interactions. BI64 binds only the monomeric capsid and locks the protein in the assembly incompetent monomeric form by disrupting capsid intersubunit interactions. We also used these assays to characterize the interaction between capsid and the host protein cleavage and polyadenylation specific factor 6 (CPSF6). Consistent with recently published results, our assays revealed CPSF6 activates capsid polymerization and preferentially binds to the preassembled hexameric capsid form similar to the small molecule compound, PF74. Furthermore, these label-free assays provide a robust method for facilitating the identification of a different class of small molecule modulators of capsid function.

Hydrolysis of cellulose in synergistic mixtures of ß-glucosidase and endo/exocellulase Cel9A from Thermobifida fusca.

The synergism between the endo/exocellulase, Cel9A, and ß-glucosidase (ßgl) of Thermobifida fusca was investigated. Wild type ßgl or S319C, a ßgl mutant with significantly improved cellobiase activity, were added to Cel9A. Both wild type and mutant ßgl enhanced the Cel9A hydrolysis of carboxymethyl cellulose (CMC) and filter paper by 50-100% compared to Cel9A alone. No enhancement occurred with addition of E388A, an inactive form of ßgl. HPLC analysis showed that, with Cel9A alone, the resulting hydrolysate of glucose and cellobiose contained about half glucose; after addition of equimolar amounts of either wild type ßgl or mutant S319C to Cel9A, the hydrolysate contained more than 85% glucose. ßgl thus acted synergistically with Cel9A by converting cello-oligomers to glucose; this reduced the soluble sugar accumulation during hydrolysis of cellulose.

A concise synthesis of tetrahydroxy-LCB, alpha-galactosyl ceramide, and 1,4-dideoxy-1,4-imino-L-ribitol via D-allosamines as key building blocks.

The total syntheses of tetrahydroxy-LCB 1, alpha-galactosyl ceramide 2, and 1,4-dideoxy-1,4-imino-L-ribitol 3 via D-allosamine derivatives as common synthons are described here.

Regioselective glycosylation of neamine core: a facile entry to kanamycin B related analogues.

[reaction: see text] Introduction of a sugar unit at either the O5 or O6 position of various neamine derivatives in excellent selectivity and yields is described here. Application to the synthesis of kanamycin analogues is also highlighted.