A 22-pJ/spike 73-Mspikes/s 130k-compartment neural array transceiver with conductance-based synaptic and membrane dynamics

Neuromorphic cognitive computing offers a bio-inspired means to approach the natural intelligence of biological neural systems in silicon integrated circuits. Typically, such circuits either reproduce biophysical neuronal dynamics in great detail as tools for computational neuroscience, or abstract away the biology by simplifying the functional forms of neural computation in large-scale systems for machine intelligence with high integration density and energy efficiency. Here we report a hybrid which offers biophysical realism in the emulation of multi-compartmental neuronal network dynamics at very large scale with high implementation efficiency, and yet with high flexibility in configuring the functional form and the network topology. The integrate-and-fire array transceiver (IFAT) chip emulates the continuous-time analog membrane dynamics of 65 k two-compartment neurons with conductance-based synapses. Fired action potentials are registered as address-event encoded output spikes, while the four types of synapses coupling to each neuron are activated by address-event decoded input spikes for fully reconfigurable synaptic connectivity, facilitating virtual wiring as implemented by routing address-event spikes externally through synaptic routing table. Peak conductance strength of synapse activation specified by the address-event input spans three decades of dynamic range, digitally controlled by pulse width and amplitude modulation (PWAM) of the drive voltage activating the log-domain linear synapse circuit. Two nested levels of micro-pipelining in the IFAT architecture improve both throughput and efficiency of synaptic input. This two-tier micro-pipelining results in a measured sustained peak throughput of 73 Mspikes/s and overall chip-level energy efficiency of 22 pJ/spike. Non-uniformity in digitally encoded synapse strength due to analog mismatch is mitigated through single-point digital offset calibration. Combined with the flexibly layered and recurrent synaptic connectivity provided by hierarchical address-event routing of registered spike events through external memory, the IFAT lends itself to efficient large-scale emulation of general biophysical spiking neural networks, as well as rate-based mapping of rectified linear unit (ReLU) neural activations

Programmable site-selective labeling of oligonucleotides based on carbene catalysis

Site-selective modification of oligonucleotides serves as an indispensable tool in many fields of research including research of fundamental biological processes, biotechnology, and nanotechnology. Here we report chemo- and regioselective modification of oligonucleotides based on rhodium(I)-carbene catalysis in a programmable fashion. Extensive screening identifies a rhodium(I)-catalyst that displays robust chemoselectivity toward base-unpaired guanosines in single and double-strand oligonucleotides with structurally complex secondary structures. Moreover, high regioselectivity among multiple guanosines in a substrate is achieved by introducing guanosine-bulge loops in a duplex. This approach allows the introduction of multiple unique functional handles in an iterative fashion, the utility of which is exemplified in DNA-protein cross-linking in cell lysates. The methods for investigation of DNA-binding proteins require site-selective chemical modifications to be introduced into oligonucleotides. Here, the authors report a chemo- and regioselective method for the modification of unpaired guanosines in single- and double-stranded oligonucleotides, based on Rh(I)-carbene catalysis

The HIV Genomic Incidence Assay Meets False Recency Rate and Mean Duration of Recency Infection Performance Standards.

HIV incidence is a primary metric for epidemic surveillance and prevention efficacy assessment. HIV incidence assay performance is evaluated via false recency rate (FRR) and mean duration of recent infection (MDRI). We conducted a meta-analysis of 438 incident and 305 chronic specimens' HIV envelope genes from a diverse global cohort. The genome similarity index (GSI) accurately characterized infection stage across diverse host and viral factors. All except one chronic specimen had GSIs below 0.67, yielding a FRR of 0.33 [0-0.98] %. We modeled the incidence assay biomarker dynamics with a logistic link function assuming individual variabilities in a Beta distribution. The GSI probability density function peaked close to 1 in early infection and 0 around two years post infection, yielding MDRI of 420 [361, 467] days. We tested the assay by newly sequencing 744 envelope genes from 59 specimens of 21 subjects who followed from HIV negative status. Both standardized residuals and Anderson-Darling tests showed that the test dataset was statistically consistent with the model biomarker dynamics. This is the first reported incidence assay meeting the optimal FRR and MDRI performance standards. Signatures of HIV gene diversification can allow precise cross-sectional surveillance with a desirable temporal range of incidence detection

Sequences of the Cytochrome C Oxidase Subunit I (COI) Gene are Suitable for Species Identification of Korean Calliphorinae Flies of Forensic Importance (Diptera: Calliphoridae)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75068/1/j.1556-4029.2009.01126.x.pd

Helicobacter pylori infection induces STAT3 phosphorylation on Ser727 and autophagy in human gastric epithelial cells and mouse stomach

© 2020, The Author(s).Helicobacter pylori (H. pylori) infection is considered as one of the principal risk factors of gastric cancer. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) plays an important role in inflammation-associated gastric carcinogenesis. In the canonical STAT3 pathway, phosphorylation of STAT3 on Tyr705 is a major event of STAT3 activation. However, recent studies have demonstrated that STAT3 phosphorylated on Ser727 has an independent function in mitochondria. In the present study, we found that human gastric epithelial AGS cells infected with H. pylori resulted in localization of STAT3 phosphorylated on Ser727 (P-STAT3Ser727), predominantly in the mitochondria. Notably, H. pylori-infected AGS cells exhibited the loss of mitochondrial integrity and increased expression of the microtubule-associated protein light chain 3 (LC3), the autophagosomal membrane-associated protein. Treatment of AGS cells with a mitophagy inducer, carbonyl cyanide 3-chlorophenylhydrazone (CCCP), resulted in accumulation of P-STAT3Ser727 in mitochondria. In addition, the elevated expression and mitochondrial localization of LC3 induced by H. pylori infection were attenuated in AGS cells harboring STAT3 mutation defective in Ser727 phosphorylation (S727A). We also observed that both P-STAT3Ser727 expression and LC3 accumulation were increased in the mitochondria of H. pylori-inoculated mouse stomach.

Assessment of Deceased Donor Kidneys Using a Donor Scoring System

∙The authors have no financial conflicts of interest. Purpose: Marginal grafts should be used more actively in Asian countries where deceased donor transplantation is unpopular. We modified a quantitative donor scoring system proposed by Nyberg and his colleagues and developed a donor scoring system in order to assess the quality of deceased donor grafts and their prognostic value as an initial effort to promote usage of marginal donors. Materials and Methods: We retrospectively evaluated 337 patients. Results: A scoring system was derived from six donor variables [age, 0-25; renal function, 0-4; history of hypertension

The Kondo effect in ferromagnetic atomic contacts

Iron, cobalt and nickel are archetypal ferromagnetic metals. In bulk, electronic conduction in these materials takes place mainly through the $s$ and $p$ electrons, whereas the magnetic moments are mostly in the narrow $d$-electron bands, where they tend to align. This general picture may change at the nanoscale because electrons at the surfaces of materials experience interactions that differ from those in the bulk. Here we show direct evidence for such changes: electronic transport in atomic-scale contacts of pure ferromagnets (iron, cobalt and nickel), despite their strong bulk ferromagnetism, unexpectedly reveal Kondo physics, that is, the screening of local magnetic moments by the conduction electrons below a characteristic temperature. The Kondo effect creates a sharp resonance at the Fermi energy, affecting the electrical properties of the system;this appears as a Fano-Kondo resonance in the conductance characteristics as observed in other artificial nanostructures. The study of hundreds of contacts shows material-dependent lognormal distributions of the resonance width that arise naturally from Kondo theory. These resonances broaden and disappear with increasing temperature, also as in standard Kondo systems. Our observations, supported by calculations, imply that coordination changes can significantly modify magnetism at the nanoscale. Therefore, in addition to standard micromagnetic physics, strong electronic correlations along with atomic-scale geometry need to be considered when investigating the magnetic properties of magnetic nanostructures.Comment: 7 pages, 5 figure