A unified framework for perceived magnitude and discriminability of sensory stimuli.

The perception of sensory attributes is often quantified through measurements of sensitivity (the ability to detect small stimulus changes), as well as through direct judgments of appearance or intensity. Despite their ubiquity, the relationship between these two measurements remains controversial and unresolved. Here, we propose a framework in which they arise from different aspects of a common representation. Specifically, we assume that judgments of stimulus intensity (e.g., as measured through rating scales) reflect the mean value of an internal representation, and sensitivity reflects a combination of mean value and noise properties, as quantified by the statistical measure of Fisher information. Unique identification of these internal representation properties can be achieved by combining measurements of sensitivity and judgments of intensity. As a central example, we show that Weber's law of perceptual sensitivity can coexist with Stevens' power-law scaling of intensity ratings (for all exponents), when the noise amplitude increases in proportion to the representational mean. We then extend this result beyond the Weber's law range by incorporating a more general and physiology-inspired form of noise and show that the combination of noise properties and sensitivity measurements accurately predicts intensity ratings across a variety of sensory modalities and attributes. Our framework unifies two primary perceptual measurements-thresholds for sensitivity and rating scales for intensity-and provides a neural interpretation for the underlying representation.

Single-Shot Readout of a Solid-State Electron Spin Qutrit.

Quantum systems usually feature a rich multilevel structure with promising resources for developing superior quantum technologies compared with their binary counterpart. Single-shot readout of these high-dimensional quantum systems is essential for exploiting their potential. Although there have been various high-spin systems, the single-shot readout of the overall state of high-spin systems remains a challenging issue. Here we demonstrate a reliable single-shot readout of spin qutrit state in a low-temperature solid-state system utilizing a binary readout scheme. We achieve a single-shot readout of an electron spin qutrit associated with a single nitrogen-vacancy center in diamond with an average fidelity of 87.80%. We use this spin qutrit system to verify quantum contextuality, a fundamental test of quantum mechanics. We observe a violation of the noncontextual hidden variable inequality with the developed single-shot readout in contrast to the conventional binary readout. These results pave the way for developing quantum information processing based on spin qutrits.

A Systematic Review of the Application of Computational Technology in Microtia.

Microtia is a congenital and morphological anomaly of one or both ears, which results from a confluence of genetic and external environmental factors. Up to now, extensive research has explored the potential utilization of computational methodologies in microtia and has obtained promising results. Thus, the authors reviewed the achievements and shortcomings of the research mentioned previously, from the aspects of artificial intelligence, computer-aided design and surgery, computed tomography, medical and biological data mining, and reality-related technology, including virtual reality and augmented reality. Hoping to offer novel concepts and inspire further studies within this field.

Relay Selection for Over-the-Air Computation Achieving Both Long Lifetime and High Reliability.

In a general wireless sensor network, a sink node collects data from each node successively and then post-processes the data to obtain useful information. However, conventional methods have a scalability problem: the data collection/processing time increases with the number of nodes, and frequent transmission collisions degrade spectrum efficiency. If only statistical values of the data are needed, using over-the-air computation (AirComp) can efficiently perform data collection and computation. However, AirComp also has its problems: when the channel gain of a node is too low, (i) the transmission power of that node will be high, decreasing the lifetime of that node and the entire network, and (ii) sometimes, the computation error still occurs even though the maximal transmission power is used. To jointly solve these two problems, in this paper we investigate the relay communication for AirComp and study a relay selection protocol. The basic method selects an ordinary node with a good channel condition as a relay node, considering both computation error and power consumption. This method is further enhanced to explicitly consider network lifetime in relay selection. Extensive simulation evaluations confirm that the proposed method helps to prolong the lifetime of the entire network and reduce computation errors as well.

Mitochondrial DNA enables AIM2 inflammasome activation and hepatocyte pyroptosis in nonalcoholic fatty liver disease.

Mitochondria damage exacerbates NAFLD through trigerring AIM2 inflammasome activation and hepatocyte pyroptosis. This study provides novel insights into the underlying mechanisms of mitochondrial DNA synthesis in NAFLD and also suggests potential therapeutic targets for the treatment of NAFLD.

Silencing of microRNA-135b inhibits invasion, migration, and stemness of CD24+CD44+ pancreatic cancer stem cells through JADE-1-dependent AKT/mTOR pathway.

BACKGROUND: Recent studies have emphasized determining the ability of microRNAs (miRNAs) as crucial regulators in the occurrence and development of pancreatic cancer (PC), which continues to be one of the deadliest malignancies with few effective therapies. The study aimed to investigate the functional role of miR-135b and its associated mechanism to unravel the biological characteristics of tumor growth in pancreatic cancer stem cells (PCSCs). METHODS: Microarray analyses were initially performed to identify the PC-related miRNAs and genes. The expression of miR-135b and PCSC markers in PC tissues and cells was determined by RT-qPCR and western blot analysis, respectively. The potential gene (JADE-1) that could bind to miR-135b was confirmed by the dual-luciferase reporter assay. To investigate the tumorigenicity, migration, invasion, and stemness of PC cells, several gain-of-function and loss-of-function genetic experiments were conducted. Finally, tumor formation in nude mice was conducted to confirm the results in vivo. RESULTS: miR-135b was highly-expressed in PC tissues and PCSCs, which was identified to specifically target JADE-1. The overexpression of miR-135b promoted proliferation, migration, and invasion of PCSC, inhibited cell apoptosis and increased the expression of stemness-related factors (Sox-2, Oct-4, Nanog, Aldh1, and Slug). Moreover, miR-135b could promote the expression of phosphorylated AKT and phosphorylated mTOR in the AKT/mTOR pathway. Additionally, miR-135b overexpression accelerated tumor growth in nude mice. CONCLUSIONS: Taken together, the silencing of miR-135b promotes the JADE-1 expression, which inactivates the AKT/mTOR pathway and ultimately results in inhibition of self-renewal and tumor growth of PCSCs. Hence, this study contributes to understanding the role of miR-135 in PCSCs and its underlying molecular mechanisms to aid in the development of effective PC therapeutics.

Predicting neuronal dynamics with a delayed gain control model.

Visual neurons respond to static images with specific dynamics: neuronal responses sum sub-additively over time, reduce in amplitude with repeated or sustained stimuli (neuronal adaptation), and are slower at low stimulus contrast. Here, we propose a simple model that predicts these seemingly disparate response patterns observed in a diverse set of measurements-intracranial electrodes in patients, fMRI, and macaque single unit spiking. The model takes a time-varying contrast time course of a stimulus as input, and produces predicted neuronal dynamics as output. Model computation consists of linear filtering, expansive exponentiation, and a divisive gain control. The gain control signal relates to but is slower than the linear signal, and this delay is critical in giving rise to predictions matched to the observed dynamics. Our model is simpler than previously proposed related models, and fitting the model to intracranial EEG data uncovers two regularities across human visual field maps: estimated linear filters (temporal receptive fields) systematically differ across and within visual field maps, and later areas exhibit more rapid and substantial gain control. The model is further generalizable to account for dynamics of contrast-dependent spike rates in macaque V1, and amplitudes of fMRI BOLD in human V1.

Associations between Personal PM2.5 Elemental Constituents and Decline of Kidney Function in Older Individuals: the China BAPE Study.

Long-term exposure to fine particulate matter (PM2.5) is associated with kidney dysfunction. However, few studies have investigated acute effects of PM2.5 elemental constituents on renal function. We evaluated associations between personal PM2.5 and its elemental constituents and kidney function, assessed by an estimated glomerular filtration rate (eGFR) in Biomarkers of Air Pollutants Exposure in the Chinese aged 60-69 study. Seventy one older individuals were visited monthly between September 2018 and January 2019. Each participant wore a PM2.5 monitor for 72 h, responded to a questionnaire, and underwent a physical examination with blood sampling. Linear mixed-effect models were used to estimate associations between personal PM2.5 elemental constituents and eGFR. We found that significant changes in eGFR from -1.69% [95% confidence interval (CI): -3.34%, -0.01%] to -3.27% (95% CI: -5.04%, -1.47%) were associated with interquartile range (IQR) increases in individual PM2.5 exposures at various lag periods (7-12, 13-24, 0-24, 25-48, and 49-72 h). An IQR increase in 72 h moving averages of copper, manganese, and titanium in personal PM2.5 corresponded to -2.34% (95% CI: -3.67%, -0.99%) to -4.56% (95% CI: -7.04%, -2.00%) changes in eGFR. Personal PM2.5 and some of its elemental constituents are inversely associated with eGFR in older individuals.

Compressive Temporal Summation in Human Visual Cortex.

Combining sensory inputs over space and time is fundamental to vision. Population receptive field models have been successful in characterizing spatial encoding throughout the human visual pathways. A parallel question, how visual areas in the human brain process information distributed over time, has received less attention. One challenge is that the most widely used neuroimaging method, fMRI, has coarse temporal resolution compared with the time-scale of neural dynamics. Here, via carefully controlled temporally modulated stimuli, we show that information about temporal processing can be readily derived from fMRI signal amplitudes in male and female subjects. We find that all visual areas exhibit subadditive summation, whereby responses to longer stimuli are less than the linear prediction from briefer stimuli. We also find fMRI evidence that the neural response to two stimuli is reduced for brief interstimulus intervals (indicating adaptation). These effects are more pronounced in visual areas anterior to V1-V3. Finally, we develop a general model that shows how these effects can be captured with two simple operations: temporal summation followed by a compressive nonlinearity. This model operates for arbitrary temporal stimulation patterns and provides a simple and interpretable set of computations that can be used to characterize neural response properties across the visual hierarchy. Importantly, compressive temporal summation directly parallels earlier findings of compressive spatial summation in visual cortex describing responses to stimuli distributed across space. This indicates that, for space and time, cortex uses a similar processing strategy to achieve higher-level and increasingly invariant representations of the visual world.SIGNIFICANCE STATEMENT Combining sensory inputs over time is fundamental to seeing. Two important temporal phenomena are summation, the accumulation of sensory inputs over time, and adaptation, a response reduction for repeated or sustained stimuli. We investigated these phenomena in the human visual system using fMRI. We built predictive models that operate on arbitrary temporal patterns of stimulation using two simple computations: temporal summation followed by a compressive nonlinearity. Our new temporal compressive summation model captures (1) subadditive temporal summation, and (2) adaptation. We show that the model accounts for systematic differences in these phenomena across visual areas. Finally, we show that for space and time, the visual system uses a similar strategy to achieve increasingly invariant representations of the visual world.

Fabrication and physicochemical and antibacterial properties of ethyl cellulose-structured cinnamon oil oleogel: relation between ethyl cellulose viscosity and oleogel performance.

BACKGROUND: Edible packaging and coating with natural antimicrobials such as essential oils is an emerging technology for the control of pathogen growth in meat products. This study aimed to explore ethyl cellulose (EC) of three viscosities for the structuring of cinnamon essential oil (CEO), and investigated the physicochemical properties of the resulting oleogel and its emulsion, as well as the corresponding antibacterial activity in model and actual environments (as in sausages). RESULTS: The network structure of CEO-EC oleogel was more compact with increased EC viscosity, thereby improving the binding capacity and stability of the oil. A positive correlation was found between EC viscosity and particle size of the CEO-EC emulsion. The 45 cP CEO-EC emulsion exhibited greatest antimicrobial activitiy in models with Escherichia coli (E. coli) O157:H7 (ATCC 700927) and Staphylococcus aureus (S. aureus) (ATCC 29213), as well as in sausage, with respect to total counts of mesophilic bacteria, psychrotrophs, lactobacilli, and pseudomonads. CONCLUSION: The CEO-EC oleogel has antibacterial activity, determined by the EC viscosity, that provide potential antibacterial protection for meat products and might be especially suitable for some traditional Chinese ready-to-eat sausages without strictly sealed packaging. © 2019 Society of Chemical Industry.

Trends in the Prevalence of Morbid Obesity among Children and Adolescents in Shandong, China, 1995-2014.

Background: Childhood obesity has increased dramatically during the past decades; however, data on the prevalence of morbid obesity is limited. The present study examined the prevalent trends in morbid obesity among children and adolescents during the past 19 years (1995-2014) in Shandong, China. Methods: Data for this study were obtained from five cross-sectional surveys (1995, 2000, 2005, 2010 and 2014) of schoolchildren in Shandong Province, China. A total of 41 500 students aged 7-18 years were included in this study. Body mass index cutoffs recommended by the International Obesity Task Force were used to define morbid obesity. Results: The prevalence of morbid obesity was increasing continuously during the past 19 years (1995-2014), from 0.25% for boys and 0.11% for girls in 1995 to 2.73% for boys and 1.29% for girls in 2014. Boys had higher prevalence of morbid obesity than girls (p<0.01). Regional socioeconomic status (SES) inequalities in morbid obesity were observed; children and adolescents from high SES district had a rapid increase in the prevalence of morbid obesity than their counterparts from moderate SES and low SES districts in the past 19 years. Conclusion: Although the current prevalence of morbid obesity was at a relatively low level, a continuous increasing trend was observed between 1995 and 2014. We should not relax our vigilance, and policymakers and experts should pay more attention to the monitoring and prevention of morbid obesity among children and adolescents in the future decades.

Percentiles of waist-hip ratio and the relationship with blood pressure among children and adolescents in Shandong, China.

BACKGROUND: Anthropometric indices such as waist circumference (WC), waist-to-height ratio (WHtR) and waist-hip ratio (WHR) have been recognized as useful alternatives to visceral fat measurement in epidemiological studies. WHR has been used extensively in adults. However, there are very few published data for WHR among children and adolescents. AIM: The present study examined the distribution of WHR and the relationship with blood pressure (BP) among children and adolescents in Shandong, PR China. SUBJECTS AND METHODS: Data for this study were obtained from a large cross-sectional survey of schoolchildren carried out in 2010. A total of 38,822 students (19,456 boys and 19,366 girls) aged 7-17 years participated in this study. WC, Hip circumference (HC), systolic blood pressure (SBP) and diastolic blood pressure (DBP) of all subjects were measured; WHR was calculated as WC divided by HC. Abdominal obesity was defined by previously published WHR references based on Chinese children and adolescents living in Beijing. All subjects were divided into two groups (group 1 with WHR <85th; group 2 with WHR ≥85th) according to the percentiles of WHR and comparisons of the SBP and DBP between the two groups were made. RESULTS: The WHR levels in Shandong boys and girls were lower than those from German and Pakistani. The overall prevalence of abdominal obesity was 9.53% (95% CI = 9.12-9.95%) for boys and 9.82% (95% CI = 9.40-10.24%) for girls, no statistical differences between the two genders were observed (p > 0.05). In both boys and girls, the Z-scores of SBP and DBP were all significantly lower in group 1 than in group 2 (p < 0.01), indicating that children and adolescents with high WHR tended to have higher BP values. CONCLUSION: WHR is useful in identifying children and adolescents at risk of developing high BP. These findings, together with the known tracking of BP from adolescence into adulthood, highlight the importance of preventing overweight and obesity among children and adolescents in order to prevent the development of hypertension in adults.

[Risk assessment and risk control for occupational exposure to chemical toxicants from an isophorone nitrile device].

OBJECTIVE: Risk assessment and risk control for occupational exposure to chemical toxicants were performed on an isophorone nitrile device with an annual production of 5,000 tons, based on improved Singaporean semi-quantitative risk assessment method, with consideration of actual situation in China and in the present project. METHODS: With the use of engineering analysis and identification of occupational hazards in the improved Singaporean semi-quantitative risk assessment method, hazard rating (HR) and risk assessment were performed on chemical toxicants from an isophorone nitrile device with an annual production of 5,000 tons. RESULTS: The chemical toxicants in the isophorone nitrile device were mainly isophorone, hydrocyanic acid, methanol, phosphoric acid, sodium hydroxide, and sodium cyanide; the HR values were mild hazard (2), extreme hazard (5), mild hazard (2), mild hazard (2), moderate hazard (3), and extreme hazard (5), respectively, and the corresponding exposure rating (ER) values were 2.09, 2.72, 2.76, 1.68, 2.0, and 1.59, respectively. The risk of chemical toxicants in this project was assessed according to the formula Risk = [HR×ER](1/2). Hydrocyanic acid was determined as high risk, sodium hydroxide and sodium cyanide as medium risk, and isophorone, methanol, and phosphoric acid as low risk. Priority in handling of risks was determined by risk rating. The table of risk control measure was established for pre-assessment of occupational hazards. CONCLUSION: With risk assessment in this study, we concluded that the isophorone nitrile device with 5,000 ton annual production was a high-occupational hazard device. This device is a project of extreme occupational hazard. The improved Singaporean semi-quantitative risk assessment method is a scientific and applicable method, and is especially suitable for pre-evaluation of on-site project with no analogy.

Disparate nonlinear neural dynamics measured with different techniques in macaque and human V1.

Diverse neuro-imaging techniques measure different aspects of neural responses with distinct spatial and temporal resolutions. Relating measured neural responses across different methods has been challenging. Here, we take a step towards overcoming this challenge, by comparing the nonlinearity of neural dynamics measured across methods. We used widefield voltage-sensitive dye imaging (VSDI) to measure neural population responses in macaque V1 to visual stimuli with a wide range of temporal waveforms. We found that stimulus-evoked VSDI responses are surprisingly near-additive in time. These results are qualitatively different from the strong sub-additive dynamics previously measured using fMRI and electrocorticography (ECoG) in human visual cortex with a similar set of stimuli. To test whether this discrepancy is specific to VSDI-a signal dominated by subthreshold neural activity, we repeated our measurements using widefield imaging of a genetically encoded calcium indicator (GcaMP6f)-a signal dominated by spiking activity, and found that GCaMP signals in macaque V1 are also near-additive. Therefore, the discrepancies in the extent of sub-additivity between the macaque and the human measurements are unlikely due to differences between sub- and supra-threshold neural responses. Finally, we use a simple yet flexible delayed normalization model to capture these different dynamics across measurements (with different model parameters). The model can potentially generalize to a broader set of stimuli, which aligns with previous suggestion that dynamic gain-control is a canonical computation contributing to neural processing in the brain.

Disentangling signal and noise in neural responses through generative modeling.

Measurements of neural responses to identically repeated experimental events often exhibit large amounts of variability. This noise is distinct from signal, operationally defined as the average expected response across repeated trials for each given event. Accurately distinguishing signal from noise is important, as each is a target that is worthy of study (many believe noise reflects important aspects of brain function) and it is important not to confuse one for the other. Here, we introduce a principled modeling approach in which response measurements are explicitly modeled as the sum of samples from multivariate signal and noise distributions. In our proposed method-termed Generative Modeling of Signal and Noise (GSN)-the signal distribution is estimated by subtracting the estimated noise distribution from the estimated data distribution. We validate GSN using ground-truth simulations and demonstrate the application of GSN to empirical fMRI data. In doing so, we illustrate a simple consequence of GSN: by disentangling signal and noise components in neural responses, GSN denoises principal components analysis and improves estimates of dimensionality. We end by discussing other situations that may benefit from GSN's characterization of signal and noise, such as estimation of noise ceilings for computational models of neural activity. A code toolbox for GSN is provided with both MATLAB and Python implementations.

CPT-11 mitigates autoimmune diseases by suppressing effector T cells without affecting long-term anti-tumor immunity.

The incidence of autoimmune diseases has significantly increased over the past 20 years. Excessive host immunoreactions and disordered immunoregulation are at the core of the pathogenesis of autoimmune diseases. The traditional anti-tumor chemotherapy drug CPT-11 is associated with leukopenia. Considering that CPT-11 induces leukopenia, we believe that it is a promising drug for the control of autoimmune diseases. Here, we show that CPT-11 suppresses T cell proliferation and pro-inflammatory cytokine production in healthy C57BL/6 mice and in complete Freund's adjuvant-challenged mice. We found that CPT-11 effectively inhibited T cell proliferation and Th1 and Th17 cell differentiation by inhibiting glycolysis in T cells. We also assessed CPT-11 efficacy in treating autoimmune diseases in models of experimental autoimmune encephalomyelitis and psoriasis. Finally, we proved that treatment of autoimmune diseases with CPT-11 did not suppress long-term immune surveillance for cancer. Taken together, these results show that CPT-11 is a promising immunosuppressive drug for autoimmune disease treatment.

The association between genetic damage in peripheral blood lymphocytes and polymorphisms of three glutathione S-transferases in Chinese workers exposed to 1,3-butadiene.

1,3-Butadiene (BD) has been classified as a human carcinogen, group I; however, the relationship between polymorphisms of glutathione S-transferases that metabolize BD and chromosomal damage is not clear. The present study used sister chromatid exchange (SCE) and cytokinesis-block micronucleus (CBMN) assays to detect chromosomal damage in peripheral lymphocytes of 44 BD-exposed workers and 39 non-exposed healthy controls. PCR and PCR-RFLP were employed to detect three known glutathione S-transferase polymorphisms GSTT1, GSTM1, and GSTP1 (Ile105Val). The data demonstrated that the micronucleus (CBMN) frequency in BD-exposed workers was significantly higher than that in controls (frequency ratio (FR)=1.48, 95% CI: 1.14-1.91, P<0.01), and the CBMN frequency was higher in workers exposed to higher cumulative BD levels (FR=1.70, 95% CI: 1.28-2.27, P<0.01). However, differences in SCE frequency were not observed (FR=1.14, 95% CI: 0.81-1.61, P>0.05). Among exposed workers, chromosomal damage was related to BD exposure levels (FR=1.35, 95% CI: 1.02-1.80, P<0.05); age, older workers exhibited higher MN frequencies than younger workers (FR=1.45, 95% CI: 1.14-1.84, P<0.05); and years of work, those with more years of work exhibited higher MN frequencies than those with fewer years (FR=1.40, 95% CI: 1.10-1.77, P<0.05). Multivariate Poisson regression analysis showed that those who carried GSTM1 (-) (FR=1.48, 95% CI: 1.14-1.92) or GSTT1 (-) (FR=1.42, 95% CI: 1.10-1.83) genotypes, and especially those who carried both (FR=2.10, 95% CI: 1.43-3.09) exhibited significantly higher MN frequencies than those carrying GSTM1 (+), GSTT1 (+) genotypes or their combination. The GSTP1 Val genotype did not affect MN frequency (P>0.05). Our results suggested that higher levels of BD exposure in the workplace resulted in increased chromosomal damage, and that polymorphisms in GSTT1 and GSTM1 genes might modulate the genotoxic effects of BD exposure. Furthermore, the GSTT1 and GSTM1 polymorphisms exhibited an additive effect. Finally, urinary DHBMA was found to provide a biomarker that correlated with airborne BD levels.

Differentially expressed protein-coding genes in ankylosing spondylitis: Emerging insights into pathogenesis and therapeutic approaches.

Ankylosing spondylitis (AS) is a chronic, progressive inflammatory rheumatic disease affecting the spine, axial skeleton, and sacroiliac joints. Pathogenesis of AS encompasses enthesitis, synovitis, and osteoproliferation, leading to the formation of syndesmophytes, ankylosis, and spinal rigidity. Bioinformatics, an interdisciplinary field combining computer science, mathematics, and biology, enables the analysis of complex biological data for investigating AS pathogenesis. This review summarizes differentially expressed protein-coding genes in peripheral blood or local tissues of AS patients compared with healthy controls and comprehensively reviews currently available therapeutic agents. The objective is to enhance the understanding of AS pathogenesis, inform diagnosis, identify novel therapeutic targets, and facilitate personalized medicine. This review contributes to a deeper understanding of AS pathogenesis and provides a foundation for developing innovative therapeutic approaches.

High fructose diet: A risk factor for immune system dysregulation.

Excessive intake of sweets is a predisposing factor for metabolic disorders, and fructose, as one of the major dietary sugars in the diet, has been shown to be a major cause of obesity, diabetes, and metabolic syndrome. These disorders are usually associated with immune dysfunction. Therefore, exploring the effects of a high fructose diet on the immune system may provide insight into the underlying mechanisms of these diseases. We synthesized the available evidence to suggest that excessive fructose intake disrupts the body's immune homeostasis by promoting immune cell metabolic rearrangements, alterations in gut microbial community structure, and intestinal barrier permeability. Indeed, not only does fructose itself affect immune system homeostasis, but its metabolites also have a profound influence. The metabolites from fructolysis are mainly produced in the small intestine and liver and subsequently enter the systemic circulation. Elevated levels of fructose metabolites, such as uric acid, FFAs, and lactate, are closely associated with oxidative stress and local tissue and organ inflammatory responses. In this review, we will focus on the link between fructose and inflammatory responses. In the meanwhile, we will also briefly summarize the studies of cancer development and immune escape mediated by fructose, as it might be beneficial for cancer immunotherapy.