Miracle-dz/UniFAR-FTUs huggingface dataset:
No Effects of Anodal tDCS on Local GABA and Glx Levels in the Left Posterior Superior Temporal Gyrus

A number of studies investigating the biological effects of transcranial direct current stimulation (tDCS) using magnetic resonance spectroscopy (MRS) have found that it may affect local levels of γ-aminobutyric acid (GABA), glutamate and glutamine (commonly measured together as “Glx” in spectroscopy), and N-acetyl aspartate (NAA), however, these effects depend largely on the stimulation parameters used and the cortical area targeted. Given that different cortical areas may respond to stimulation in different ways, the purpose of this experiment was to assess the as yet unexplored biological effects of tDCS in the posterior superior temporal gyrus (pSTG), an area that has attracted some attention as a potential target for the treatment of auditory verbal hallucinations in schizophrenia patients. Biochemical changes were monitored using continuous, online MRS at a field strength of 3 Tesla. Performing intrascanner stimulation, with continuous spectroscopy before, during and after stimulation, permitted the assessment of acute effects of tDCS that would otherwise be lost when simply comparing pre- and post-stimulation differences. Twenty healthy participants underwent a repeated-measures experiment in which they received both active anodal and sham intrascanner stimulation in a stratified, randomized, double-blind experiment. No significant changes in GABA, Glx, or NAA levels were observed as a result of anodal stimulation, or between active and sham stimulation, suggesting that a single session of anodal tDCS to the pSTG may be less effective than in other cortical areas that have been similarly investigated.
Sex Differences in Nociceptin/Orphanin FQ Peptide Receptor-Mediated Pain and Anxiety Symptoms in a Preclinical Model of Post-traumatic Stress Disorder

Nociceptin/Orphanin FQ (N/OFQ) is a neuropeptide that modulates pain transmission, learning/memory, stress, anxiety, and fear responses via activation of the N/OFQ peptide (NOP or ORL1) receptor. Post-traumatic stress disorder (PTSD) is an anxiety disorder that may arise after exposure to a traumatic or fearful event, and often is co-morbid with chronic pain. Using an established animal model of PTSD, single-prolonged stress (SPS), we were the first to report that NOP receptor antagonist treatment reversed traumatic stress-induced allodynia, thermal hyperalgesia, and anxiety-like behaviors in male Sprague-Dawley rats. NOP antagonist treatment also reversed SPS-induced serum and CSF N/OFQ increase and circulating corticosterone decrease. The objective of this study was to examine the role of the NOP receptor in male and female rats subjected to traumatic stress using Wistar wild type (WT) and NOP receptor knockout (KO) rats. The severity of co-morbid allodynia was assessed as change in paw withdrawal threshold (PWT) to von Frey and paw withdrawal latency (PWL) to radiant heat stimuli, respectively. PWT and PWL decreased in male and female WT rats within 7 days after SPS, and remained decreased through day 28. Baseline sensitivity did not differ between genotypes. However, while male NOP receptor KO rats were protected from SPS-induced allodynia and thermal hypersensitivity, female NOP receptor KO rats exhibited tactile allodynia and thermal hypersensitivity to the same extent as WT rats. Male NOP receptor KO rats had a lower anxiety index (AI) than WT, but SPS did not increase AI in WT males. In contrast, SPS significantly increased AI in WT and NOP receptor KO female rats. SPS increased circulating N/OFQ levels in male WT, but not in male NOP receptor KO, or WT or KO female rats. These results indicate that the absence of the NOP receptor protects males from traumatic-stress-induced allodynia and hyperalgesia, consistent with our previous findings utilizing a NOP receptor antagonist. However, female NOP receptor KO rats experience allodynia, hyperalgesia and anxiety-like symptoms to the same extent as WT females following SPS. This suggests that endogenous N/OFQ-NOP receptor signaling plays an important, but distinct, role in males and females following exposure to traumatic stress.
A Host Factor GPNMB Restricts Porcine Circovirus Type 2 (PCV2) Replication and Interacts With PCV2 ORF5 Protein

Porcine circovirus type 2 (PCV2) is the infectious agent of postweaning multisystemic wasting syndrome (PMWS). The recently discovered open reading frame 5 (ORF5) in PCV2 genome encodes a non-structural protein. Previous study revealed that ORF5 protein inhibits cell proliferation and may interact with host transmembrane glycoprotein NMB (GPNMB). However, whether the GPNMB affects PCV2 replication and the underlying molecular mechanisms are still unknown. In this study, the transcriptome maps of PCV2-infected and ORF5-transfected porcine alveolar macrophages 3D4/2 (PAM) cells were profiled. The GPNMB gene was down-regulated in PCV2-infected and ORF5-transfected PAMs. By using glutathione S-transferase (GST) pull-down, co-immunoprecipitation (co-IP) and confocal microscopy approaches, we convincingly showed that PCV2 ORF5 protein interacts with GPNMB. Furthermore, by utilizing lentivirus mediated overexpression or knockdown approach, we showed that the cellular GPNMB significantly inhibits PCV2 replication and ORF5 expression. Moreover, GPNMB overexpressing leads to an increased Cyclin A expression and a reduced S phase, whereas GPNMB knockdown causes a decreased Cyclin A expression and a prolonged S phase. In conclusion, we identified a novel host factor GPNMB that interacts with PCV2 ORF5 protein and restricts PCV2 replication.
Mutations Defining Patient Cohorts With Elevated PD-L1 Expression in Gastric Cancer

The immunotherapy agent pembrolizumab has been approved for gastric cancer (GC) patients with recurrent or advanced disease who are PD-L1 positive. Mutations in the primary lesion may drive the expression of immune targets thereby priming the tumor to therapeutic sensitivity. In this study, we aimed to uncover mutations associated with elevated PD-L1 expression in GC patients. Data from 410 GC patients were available, including the mutational spectrum of 39,916 genes and expression values of 20,500 genes. PD-L1 gene expression was compared to the mutational status of each gene separately by using a Mann-Whitney U-test and a Receiver Operating Characteristic test. Only mutations with a prevalence over 5% were considered. Significance was accepted in cases of p < 1E-05 and a fold change over 1.44. Mutations in 209 genes were associated with increased PD-L1 expression. These mutations were enriched in genes related to microtubule-based movement (p = 3.4E-4), cell adhesion (p = 4.9E-4), response to DNA-damage (p = 6.9E-4), and double-strand break-repair (p = 1.6E-3). Mutations in TTK (p = 8.8E-10, AUC = 0.77), COL7A1 (p = 2.0E-9, AUC = 0.74), KIF15 (p = 2.5E-9, AUC = 0.75), and BDP1 (p = 3.3E-9, AUC = 0.74) had the strongest link to elevated PD-L1 expression. Finally, we established a decision tree based on mutations in PIK3CA, MEF2C, SLC11A1, and KIF15 capable to separate patient sub-cohorts with elevated PD-L1 expression. In summary, we identified mutations associated with elevated PD-L1 expression that facilitate the development of better prognostic biomarkers for GC, and might offer insight into the underlying tumor biology.
A Comparison of Homogenization vs. Enzymatic Lysis for Microbiome Profiling in Clinical Endoscopic Biopsy Tissue Samples

Identification of the human microbiome has proven to be of utmost importance with the emerging role of bacteria in various physiological and pathological processes. High throughput sequencing strategies have evolved to assess the composition of the microbiome. To identify possible bias that may exist in the processing of tissue for whole genome sequencing (WGS), it is important to evaluate the extraction method on the overall microbial content and composition. Here we compare two different methods of extraction, homogenization vs. enzymatic lysis, on gastric, esophageal and colorectal biopsies and survey the microbial content and composition using WGS and quantitative PCR (qPCR). We examined total bacterial content using universal 16S rDNA qPCR as well as the abundance of three phyla (Actinobacter, Firmicutes, Bacteroidetes) and one genus (Fusobacterium). We found minimal differences between the two extraction methods in the overall community structure. Furthermore, based on our qPCR analysis, neither method demonstrated preferential extraction of any particular clade of bacteria, nor significantly altered the detection of Gram-positive or Gram-negative organisms. However, although the overall microbial composition remained very similar and the most prevalent bacteria could be detected effectively using either method, the precise community structure and microbial abundances between the two methods were different, primarily due to variations in detection of low abundance genus. We also demonstrate that the homogenization extraction method provides higher microbial DNA content and higher read counts from human tissue biopsy samples of the gastrointestinal tract.
Orexin Receptor Blockade-Induced Sleep Preserves the Ability to Wake in the Presence of Threat in Mice

Retention of the ability to wake from sleep in response to dangerous situations is an ideal characteristic of safe hypnotics. We studied the effects of a dual orexin receptor antagonist-22 (DORA-22) and the GABA-A receptor modulator, triazolam, on the ability to wake in response to aversive stimuli. We examined four modalities of sensory inputs, namely, auditory (ultrasonic sound), vestibular (trembling), olfactory (predator odor), and autonomic (hypoxia) stimuli. When the mice fell asleep, one of the four stimuli was applied for 30 s. In the case of auditory stimulation, latency to arousal following vehicle, DORA-22, and triazolam administration was 3.0 (2.0–3.8), 3.5 (2.0–6.5), and 161 (117–267) s (median and 25–75 percentile in the parentheses, n = 8), respectively. Latency to return to sleep after arousal was 148 (95–183), 70 (43–98), and 60 (52–69) s, respectively. Similar results were obtained for vestibular and olfactory stimulation. During the hypoxic stimulation, latencies for arousal and returning to sleep were not significantly different among the groups. The findings of this study are consistent with the distinct mechanisms of these sleep promoting therapies; GABA-A receptor activation by triazolam is thought to induce widespread central nervous system (CNS) suppression while DORA-22 more specifically targets sleep/wake pathways through orexin receptor antagonism. These data support the notion that DORA-22 preserves the ability to wake in response to aversive and consciousness-inducing sensory stimuli, regardless of modality, while remaining effective in the absence of threat. This study provides a unique and important safety evaluation of the potential for certain hypnotics.
Biomolecules Turn Self-Assembling Amphiphilic Block Co-polymer Platforms Into Biomimetic Interfaces

Biological membranes constitute an interface between cells and their surroundings and form distinct compartments within the cell. They also host a variety of biomolecules that carry out vital functions including selective transport, signal transduction and cell-cell communication. Due to the vast complexity and versatility of the different membranes, there is a critical need for simplified and specific model membrane platforms to explore the behaviors of individual biomolecules while preserving their intrinsic function. Information obtained from model membrane platforms should make invaluable contributions to current and emerging technologies in biotechnology, nanotechnology and medicine. Amphiphilic block co-polymers are ideal building blocks to create model membrane platforms with enhanced stability and robustness. They form various supramolecular assemblies, ranging from three-dimensional structures (e.g., micelles, nanoparticles, or vesicles) in aqueous solution to planar polymer membranes on solid supports (e.g., polymer cushioned/tethered membranes,) and membrane-like polymer brushes. Furthermore, polymer micelles and polymersomes can also be immobilized on solid supports to take advantage of a wide range of surface sensitive analytical tools. In this review article, we focus on self-assembled amphiphilic block copolymer platforms that are hosting biomolecules. We present different strategies for harnessing polymer platforms with biomolecules either by integrating proteins or peptides into assemblies or by attaching proteins or DNA to their surface. We will discuss how to obtain synthetic structures on solid supports and their characterization using different surface sensitive analytical tools. Finally, we highlight present and future perspectives of polymer micelles and polymersomes for biomedical applications and those of solid-supported polymer membranes for biosensing.
MADS-Box Gene Classification in Angiosperms by Clustering and Machine Learning Approaches

The MADS-box gene family is an important transcription factor family involved in floral organogenesis. The previously proposed ABCDE model suggests that different floral organ identities are controlled by various combinations of classes of MADS-box genes. The five-class ABCDE model cannot cover all the species of angiosperms, especially the orchid. Thus, we developed a two-stage approach for MADS-box gene classification to advance the study of floral organogenesis of angiosperms. First, eight classes of reference datasets (A, AGL6, B12, B34, BPI, C, D, and E) were curated and clustered by phylogenetic analysis and unsupervised learning, and they were confirmed by the literature. Second, feature selection and multiple prediction models were curated according to sequence similarity and the characteristics of the MADS-box gene domain using support vector machines. Compared with the BindN and COILS features, the local BLAST model yielded the best accuracy. For performance evaluation, the accuracy of Phalaenopsis aphrodite MADS-box gene classification was 93.3%, which is higher than 86.7% of our previous classification prediction tool, iMADS. Phylogenetic tree construction – the most common method for gene classification yields classification errors and is time-consuming for analysis of massive, multi-species, or incomplete sequences. In this regard, our new system can also confirm the classification errors of all the random selection that were incorrectly classified by phylogenetic tree analysis. Our model constitutes a reliable and efficient MADS-box gene classification system for angiosperms.
Effects of High-Definition Transcranial Direct Current Stimulation (HD-tDCS) of the Intraparietal Sulcus and Dorsolateral Prefrontal Cortex on Working Memory and Divided Attention

Objective: There is a need to elucidate the underlying neural mechanisms subserving working memory and divided attention functioning. Recent neuroimaging studies provide evidence for anatomical co-localization of both functions. In the present study we used a functional intervention, whereby we applied a novel type of focalised, non-invasive brain stimulation, High-Definition transcranial Direct Current Stimulation (HD-tDCS), to the regions subserving these processes, the left intraparietal sulcus (IPS) and left dorsolateral prefrontal cortex (LDLPFC). Our aim was therefore to modulate activity in these regions using HD-tDCS and thereby assess their relevance for working memory, divided attention and their shared sub-processes. Method: 78 participants were evenly randomized to one of three conditions in a single blind, parallel group study design. Anodal or sham HD-tDCS was applied to either the left IPS or LDLPFC while participants completed a verbal working memory task, a divided attention task, and two tasks measuring subcomponents of working memory (updating and maintenance). Results: Focalised stimulation of the IPS and LDLPFC did not significantly modulate performance compared to sham stimulation. However, moderate effect sizes were obtained for at least one HD-tDCS condition relative to sham for all tasks, warranting further research into the functional importance of the IPS in subserving these abilities. Conclusions: The current results may be useful for informing future tDCS studies for modulating working memory and divided attention functioning.
Rapid Succession of Actively Transcribing Denitrifier Populations in Agricultural Soil During an Anoxic Spell

Denitrification allows sustained respiratory metabolism during periods of anoxia, an advantage in soils with frequent anoxic spells. However, the gains may be more than evened out by the energy cost of producing the denitrification machinery, particularly if the anoxic spell is short. This dilemma could explain the evolution of different regulatory phenotypes observed in model strains, such as sequential expression of the four denitrification genes needed for a complete reduction of nitrate to N2, or a “bet hedging” strategy where all four genes are expressed only in a fraction of the cells. In complex environments such strategies would translate into progressive onset of transcription by the members of the denitrifying community. We exposed soil microcosms to anoxia, sampled for amplicon sequencing of napA/narG, nirK/nirS, and nosZ genes and transcripts after 1, 2 and 4 h, and monitored the kinetics of NO, N2O, and N2. The cDNA libraries revealed a succession of transcribed genes from active denitrifier populations, which probably reflects various regulatory phenotypes in combination with cross-talks via intermediates (NO2−, NO) produced by the “early onset” denitrifying populations. This suggests that the regulatory strategies observed in individual isolates are also displayed in complex communities, and pinpoint the importance for successive sampling when identifying active key player organisms.
Acquisition Behavior of Emerging Versus Developed Market Multinationals

The purpose of this paper is to investigate how emerging and developed market multinationals (EMMs and DMMs) differ in their acquisition behavior (vis-à-vis the choice of partial versus full acquisitions) when entering a developed market economy, Japan. We hypothesize that EMMs prefer partial acquisitions, whereas DMMs prefer full acquisitions due to what we call the country-of-origin effect. Additionally, we hypothesize that this country-of-origin effect is more pronounced for smaller firms. The results, based upon 224 strategic cross-border acquisitions in Japan, support these two hypotheses. This study contributes to the literature on EMMs.
Rate-constrained picture-adaptive quantization for JPEG baseline coders

A recursive algorithm is presented for generating quantization tables in JPEG (Joint Photographic Experts Group) baseline coders from the actual statistics of the input image. Starting from a quantization table with large step sizes, corresponding to low bit rate and high distortion, one entry of the quantization table is updated at a time so that, at each step, the ratio of decrease in distortion to increase in bit rate is approximately maximized. This procedure is repeated until a target bit rate is reached. Simulation results demonstrate that, with picture-adaptive quantization tables designed by the proposed algorithm, the JPEG DCT (discrete cosine transform) coder is able to compress images with better rate-distortion performance than that achievable with conventional empirically designed quantization tables. <<ETX>>
A 6.8 TOPS/W Energy Efficiency, 1.5µW Power Consumption, Pulse Width Modulation Neuromorphic Circuits for Near-Data Computing with SSD

This paper proposes Pulse Width Modulation Neuromorphic (PWMNM) circuits, best suitable for near-data computing with SSD. The concept of neuromorphic computing is mimicking human brain with a number of mimicked-neurons of analog circuits. A mimicked-neuron in proposed PWMNM consists of 10 pairs of oscillators & clock counters, a micro controller and a charge pump. Proposed PWMNM achieves high energy efficiency of 6.8TOPS/W (Tera operations per second per Watt) and low power consumption of 1. 5µW, thanks to matrix product operations are processed with number of output pulses as a function of the time instead of conventional current or voltage operation. Both proposed PWMNM and peripheral circuits of NAND flash memory are fabricated with a 180nm standard CMOS process and PWMNM can be embedded in SSD. Character recognition system is demonstrated by using proposed PWMNM, and the recognition accuracy of 93.3% is achieved.
A 12-Gb/s AC-Coupled FFE TX With Adaptive Relaxed Impedance Matching Achieving Adaptation Range of 35-75Ω Z0 and 30-550Ω RRX

A 12-Gb/s feed forward equalizing transmitter which automatically adapts to arbitrary impedances of AC-coupled channels and receivers is proposed for the first time. The proposed transmitter detects impedances of the channel and the receiver within 8% and 5% errors, respectively, and adaptively relaxes its impedance matching to maximize eye size at cost of a negligible penalty in signal integrity. In experiment, the proposed transmitter adapted to any combination of a channel impedance of 35-75Ω and a receiver impedance of 30-550Ω while achieving eye size larger than the conventional transmitter with impedance matching. At most, a completely closed eye was increased to 136mV by the proposed transmitter.
An Asynchronous Energy-Efficient CNN Accelerator with Reconfigurable Architecture

In this paper, we introduce an asynchronous energy-efficient convolutional neural network (CNN) accelerator with reconfigurable architecture including six computing cores, each of which contains 5x5 processing elements. With the dynamically reconfigurable architecture, the data path, the calculation method, the activation function, and the pooling way and size can be modified according to the configurable information for different CNN models. In the computing cores, the global clock is replaced by the local pulse signals from Click elements. An asynchronous pipeline formed by Click elements enables the circuits to work in pipeline mode without any sacrifice of speed because of the self-timed characteristic of asynchronous circuits. Each computing core has a 5x5 registers array that is fully connected by an asynchronous Mesh network, by which the input data can be fully reused. A novel computing pattern called convolution-and-pooling-integrated computing, which combines convolution and pooling computing together, is proposed to reduce the access to the intermediate data. These yield an 88% decrease of the access to off-chip memory, which significantly reduces energy consumption. A CNN model, LeNet-5, is implemented in our accelerator with the FPGA of Xilinx VC707. The asynchronous computing core has 84% less dynamic power than that of the synchronous core. The efficiency achieves 30.03 GOPS/W, which is 2.1 times better than that of previous works.
AI Drives Domain Specific Processors

in this paper we first list some of basic requirements for domain specific processors. Then we discuss several commonly used architectures for artificial intelligence domain applications. Their pros and cons are also compared. A new architecture defined as In-Cluster Coprocessor is presented which can best utilize existing memory hierarchy in a general processor and has an easy programming model. CBC has potential advantages of power saving and low cost. Further investigation on CBC is underway.
A Second-Order Purely VCO-Based CT Δ∑ ADC Using a Modified DPLL in 40-nm CMOS

This paper presents a power-efficient purely VCO-based 2nd-order CT Δ∑ ADC featuring a modified DPLL structure. It combines a VCO with an SRO-based TDC, which enables 2nd-order noise shaping without any OTA. The nonlinearity of the front-end VCO is mitigated by putting it inside a closed loop. A multi-PFD scheme reduces the VCO center frequency and power. The proposed architecture also realizes an intrinsic tri-level DWA. A prototype ADC in 40-nm CMOS process achieves a Schreier FoM of 170.3 dB with a DR of 72.7 dB over 5.2-MHz BW, while consuming 0.91 mW under 1.1-V supply.