Hybrid Fourier domain modelocked laser utilizing a fiber optical parametric amplifier and an erbium doped fiber amplifier

To our knowledge, we report the first Fourier domain modelocked laser (FDML) constructed using optical parameter amplifier (OPA) in conjunction with an erbium-doped fiber amplifier (EDFA), centered at ~1556nm. We utilized a onepump OPA and a C-band EDFA in a series configuration with a polygon-grating wavelength filter to generate a hybrid FDML spectrum. Results demonstrate a substantially higher output power, better spectral shape and significantly more stable bandwidth than individual configurations. We believe this technique has the potential to enable several amplifiers to complement individual deficiencies resulting in improved spectral shapes and power generation for imaging applications such as optical coherence tomography (OCT). © 2010 Copyright SPIE - The International Society for Optical Engineering.published_or_final_versionThe Fiber Lasers VII: Technology, Systems, and Applications, San Francisco, CA., 25 January 2010. In Proceedings of SPIE, 2010, v. 7580, p. 1-7, article no. 75802

Radial Growth of Qilian Juniper on the Northeast Tibetan Plateau and Potential Climate Associations

There is controversy regarding the limiting climatic factor for tree radial growth at the alpine treeline on the northeastern Tibetan Plateau. In this study, we collected 594 increment cores from 331 trees, grouped within four altitude belts spanning the range 3550 to 4020 m.a.s.l. on a single hillside. We have developed four equivalent ring-width chronologies and shown that there are no significant differences in their growth-climate responses during 1956 to 2011 or in their longer-term growth patterns during the period AD 1110–2011. The main climate influence on radial growth is shown to be precipitation variability. Missing ring analysis shows that tree radial growth at the uppermost treeline location is more sensitive to climate variation than that at other elevations, and poor tree radial growth is particularly linked to the occurrence of serious drought events. Hence water limitation, rather than temperature stress, plays the pivotal role in controlling the radial growth of Sabina przewalskii Kom. at the treeline in this region. This finding contradicts any generalisation that tree-ring chronologies from high-elevation treeline environments are mostly indicators of temperature changes

A 16-nm SoC for Noise-Robust Speech and NLP Edge AI Inference With Bayesian Sound Source Separation and Attention-Based DNNs

The proliferation of personal artificial intelligence (AI) -assistant technologies with speech-based conversational AI interfaces is driving the exponential growth in the consumer Internet of Things (IoT) market. As these technologies are being applied to keyword spotting (KWS), automatic speech recognition (ASR), natural language processing (NLP), and text-to-speech (TTS) applications, it is of paramount importance that they provide uncompromising performance for context learning in long sequences, which is a key benefit of the attention mechanism, and that they work seamlessly in polyphonic environments. In this work, we present a 25-mm $^2$ system-on-chip (SoC) in 16-nm FinFET technology, codenamed SM6, which executes end-to-end speech-enhancing attention-based ASR and NLP workloads. The SoC includes: 1) FlexASR, a highly reconfigurable NLP inference processor optimized for whole-model acceleration of bidirectional attention-based sequence-to-sequence (seq2seq) deep neural networks (DNNs); 2) a Markov random field source separation engine (MSSE), a probabilistic graphical model accelerator for unsupervised inference via Gibbs sampling, used for sound source separation; 3) a dual-core Arm Cortex A53 CPU cluster, which provides on-demand single Instruction/multiple data (SIMD) fast fourier transform (FFT) processing and performs various application logic (e.g., expectation–maximization (EM) algorithm and 8-bit floating-point (FP8) quantization); and 4) an always-on M0 subsystem for audio detection and power management. Measurement results demonstrate the efficiency ranges of 2.6–7.8 TFLOPs/W and 4.33–17.6 Gsamples/s/W for FlexASR and MSSE, respectively; MSSE denoising performance allowing 6 $\times$ smaller ASR model to be stored on-chip with negligible accuracy loss; and 2.24-mJ energy consumption while achieving real-time throughput, end-to-end, and per-frame ASR latencies of 18 ms

Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity

Viruses naturally engage innate immunity, induce antigen presentation, and mediate CD8 T cell priming against foreign antigens. Polioviruses can provide a context optimal for generating antigen-specific CD8 T cells, as they have natural tropism for dendritic cells, preeminent inducers of CD8 T cell immunity; elicit Th1-promoting inflammation; and lack interference with innate or adaptive immunity. However, notorious genetic instability and underlying neuropathogenicity has hampered poliovirus-based vector applications. Here we devised a strategy based on the polio:rhinovirus chimera PVSRIPO, devoid of viral neuropathogenicity after intracerebral inoculation in human subjects, for stable expression of exogenous antigens. PVSRIPO vectors infect, activate, and induce epitope presentation in DCs in vitro; they recruit and activate DCs with Th1-dominant cytokine profiles at the injection site in vivo. They efficiently prime tumor antigen-specific CD8 T cells in vivo, induce CD8 T cell migration to the tumor site, delay tumor growth and enhance survival in murine tumor models

Clinical Significance of Physical Frailty in Subjects With Subjective Cognitive Decline: A Prospective Study With Amyloid PET Data

Background and Purpose: Physical frailty is known to be closely associated with cognitive impairment and to be an early sign of Alzheimer’s disease. We aimed to understand the characteristics of physical frailty and define factors associated with physical frailty in subjects with subjective cognitive decline (SCD) by analyzing amyloid data. Methods We prospectively enrolled subjects with SCD from a cohort study to identify predictors for the clinical progression to mild cognitive impairment or dementia from SCD (CoS-Co). All of the subjects underwent brain magnetic resonance imaging, and brain amyloid positron-emission tomography (PET) to detect amyloid beta plaques. Self-reported exhaustion, handgrip strength, and gait speed were used to measure physical frailty. Results Of 120 subjects with SCD, 26 (21.7%) were amyloid-positive in PET. Female (odds ratio [OR]=3.79, p=0.002) and amyloid-PET-positive (OR=3.80, p=0.008) subjects with SCD were at high risks of self-reported exhaustion. Amyloid PET positivity (OR=3.22, p=0.047) and high burden from periventricular white-matter hyperintensity (OR=3.34, 95% confidence interval=1.18–9.46, p=0.023) were significantly associated with a weaker handgrip. The subjects with SCD with self-reported exhaustion and weaker handgrip presented with lower cognitive performance in neuropsychological tests, especially for information processing speed and executive function. Subjects with a slower gait performed worse in visual memory function tests. Conclusions Amyloid PET positivity was associated with a higher risk of self-reported exhaustion and weaker handgrip in subjects with SCD. The subjects with SCD and physical frailty also performed worse in neuropsychological tests

Pleiotropic functions of the tumor- and metastasis-suppressing Matrix Metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice

Matrix metalloproteinase-8 (MMP-8; neutrophil collagenase) is an important regulator of innate immunity which has onco-suppressive actions in numerous tumor types

A ferroelectric memristor

Memristors are continuously tunable resistors that emulate synapses. Conceptualized in the 1970s, they traditionally operate by voltage-induced displacements of matter, but the mechanism remains controversial. Purely electronic memristors have recently emerged based on well-established physical phenomena with albeit modest resistance changes. Here we demonstrate that voltage-controlled domain configurations in ferroelectric tunnel barriers yield memristive behaviour with resistance variations exceeding two orders of magnitude and a 10 ns operation speed. Using models of ferroelectric-domain nucleation and growth we explain the quasi-continuous resistance variations and derive a simple analytical expression for the memristive effect. Our results suggest new opportunities for ferroelectrics as the hardware basis of future neuromorphic computational architectures

A reversible phospho-switch mediated by ULK1 regulates the activity of autophagy protease ATG4B

Upon induction of autophagy, the ubiquitin-like protein LC3 is conjugated to phosphatidylethanolamine (PE) on the inner and outer membrane of autophagosomes to allow cargo selection and autophagosome formation. LC3 undergoes two processing steps, the proteolytic cleavage of pro-LC3 and the de-lipidation of LC3-PE from autophagosomes, both executed by the same cysteine protease ATG4. How ATG4 activity is regulated to co-ordinate these events is currently unknown. Here we find that ULK1, a protein kinase activated at the autophagosome formation site, phosphorylates human ATG4B on serine 316. Phosphorylation at this residue results in inhibition of its catalytic activity in vitro and in vivo. On the other hand, phosphatase PP2A-PP2R3B can remove this inhibitory phosphorylation. We propose that the opposing activities of ULK1-mediated phosphorylation and PP2A-mediated dephosphorylation provide a phospho-switch that regulates the cellular activity of ATG4B to control LC3 processing

Improved Cellular Specificity of Plasmonic Nanobubbles versus Nanoparticles in Heterogeneous Cell Systems

The limited specificity of nanoparticle (NP) uptake by target cells associated with a disease is one of the principal challenges of nanomedicine. Using the threshold mechanism of plasmonic nanobubble (PNB) generation and enhanced accumulation and clustering of gold nanoparticles in target cells, we increased the specificity of PNB generation and detection in target versus non-target cells by more than one order of magnitude compared to the specificity of NP uptake by the same cells. This improved cellular specificity of PNBs was demonstrated in six different cell models representing diverse molecular targets such as epidermal growth factor receptor, CD3 receptor, prostate specific membrane antigen and mucin molecule MUC1. Thus PNBs may be a universal method and nano-agent that overcome the problem of non-specific uptake of NPs by non-target cells and improve the specificity of NP-based diagnostics, therapeutics and theranostics at the cell level

Characteristics of transposable element exonization within human and mouse

Insertion of transposed elements within mammalian genes is thought to be an important contributor to mammalian evolution and speciation. Insertion of transposed elements into introns can lead to their activation as alternatively spliced cassette exons, an event called exonization. Elucidation of the evolutionary constraints that have shaped fixation of transposed elements within human and mouse protein coding genes and subsequent exonization is important for understanding of how the exonization process has affected transcriptome and proteome complexities. Here we show that exonization of transposed elements is biased towards the beginning of the coding sequence in both human and mouse genes. Analysis of single nucleotide polymorphisms (SNPs) revealed that exonization of transposed elements can be population-specific, implying that exonizations may enhance divergence and lead to speciation. SNP density analysis revealed differences between Alu and other transposed elements. Finally, we identified cases of primate-specific Alu elements that depend on RNA editing for their exonization. These results shed light on TE fixation and the exonization process within human and mouse genes.Comment: 11 pages, 4 figure