Learnable Mixed-precision and Dimension Reduction Co-design for Low-storage Activation

Recently, deep convolutional neural networks (CNNs) have achieved many eye-catching results. However, deploying CNNs on resource-constrained edge devices is constrained by limited memory bandwidth for transmitting large intermediated data during inference, i.e., activation. Existing research utilizes mixed-precision and dimension reduction to reduce computational complexity but pays less attention to its application for activation compression. To further exploit the redundancy in activation, we propose a learnable mixed-precision and dimension reduction co-design system, which separates channels into groups and allocates specific compression policies according to their importance. In addition, the proposed dynamic searching technique enlarges search space and finds out the optimal bit-width allocation automatically. Our experimental results show that the proposed methods improve 3.54%/1.27% in accuracy and save 0.18/2.02 bits per value over existing mixed-precision methods on ResNet18 and MobileNetv2, respectively

STATISTICAL OPTIMIZATION AND STABILITY STUDY OF QUERCETIN-LOADED MICROEMULSION

Objective: This research aims to develop a quercetin microemulsion system to improve the solubility of quercetin and to study the stability of the microemulsions. Methods: The microemulsion is prepared by water titration method using isopropyl myristate (oil), Tween 60®/Span 80® (3:2) (surfactant) and ethanol (co-surfactant). Two different aqueous phases, water or NaCl solution, were used to prepare microemulsions and the influence of each parameter was described. DPPH scavenging and anti-tyrosinase activity were performed along with chemical stability to evaluate the functional stability of microemulsions. Results: The influence of percentage of oil phase (variable A) on the solubility of quercetin was less significant than that of percentage of surfactant/co-surfactant (variable B). Compared to those prepared with water (variable C), the solubility of quercetin in microemulsions prepared with NaCl solution significantly increased. The ratio of the high level to low level for solubility of three variables was 1.135, 1.315 and 1.591 respectively. Increasing variable A and B led to an increase in the particle size of microemulsions from 120.08 nm to 188.38 nm and 48.18 nm to 260.28 nm, respectively. The influence of variable B was quite significant, while variable C has no significant effect on particle size. Quercetin microemulsions showed good chemical and functional stability when stored at 4 °C. Under other conditions, especially at 40 °C, the activity of the microemulsion is considerably reduced. Conclusion: The influence of different variables on the characteristics of microemulsions was complicated. Care must be taken in the composition and storage conditions of these formulations

Pathogenesis and treatment of non-alcoholic steatohepatitis and its fibrosis

The initial presentation of non-alcoholic steatohepatitis (NASH) is hepatic steatosis. The dysfunction of lipid metabolism within hepatocytes caused by genetic factors, diet, and insulin resistance causes lipid accumulation. Lipotoxicity, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum stress would further contribute to hepatocyte injury and death, leading to inflammation and immune dysfunction in the liver. During the healing process, the accumulation of an excessive amount of fibrosis might occur while healing. During the development of NASH and liver fibrosis, the gut-liver axis, adipose-liver axis, and renin-angiotensin system (RAS) may be dysregulated and impaired. Translocation of bacteria or its end-products entering the liver could activate hepatocytes, Kupffer cells, and hepatic stellate cells, exacerbating hepatic steatosis, inflammation, and fibrosis. Bile acids regulate glucose and lipid metabolism through Farnesoid X receptors in the liver and intestine. Increased adipose tissue-derived non-esterified fatty acids would aggravate hepatic steatosis. Increased leptin also plays a role in hepatic fibrogenesis, and decreased adiponectin may contribute to hepatic insulin resistance. Moreover, dysregulation of peroxisome proliferator-activated receptors in the liver, adipose, and muscle tissues may impair lipid metabolism. In addition, the RAS may contribute to hepatic fatty acid metabolism, inflammation, and fibrosis. The treatment includes lifestyle modification, pharmacological therapy, and non-pharmacological therapy. Currently, weight reduction by lifestyle modification or surgery is the most effective therapy. However, vitamin E, pioglitazone, and obeticholic acid have also been suggested. In this review, we will introduce some new clinical trials and experimental therapies for the treatment of NASH and related fibrosis

Alterations in IL-6, IL-8, GM-CSF. TNF-α, and IFN-γ Release by Peripheral Mononuclear Cells in Patients with Active Vitiligo

The purpose of this study was to clarify the relationship between the cellular and humoral immune components in the pathogenesis of vitiligo vulgaris. By using cytokines as indicators of peripheral mononuclear cell (MNC) function, we compared the effects of phytohemagglutinin (PHA) and purified IgG on MNCs derived from patients suffering from active vitiligo with those from normal controls. The results revealed (i) a significant increase in spontaneous production of 11-6 and IL-8 in patients; (ii) PHA, purified IgG from patients (IgG-anti-MC), or IgG from normal controls (N-IgG) induced a significant increase in IL-6 but diminished GM-CSF, TNF-α, and IFN-γ release in patients; and (iii) IgG-anti-MC brought about a significantly higher stimulatory effect on IL-1β and IFN-γ production than N-IgG in normal controls. Immunologically, IL-6 can enhance melanocyte ICAM-1 expression, which may increase leukocyte-melanocyte attachment and cause melanocyte damage in vitiligo. A decrease in GM-CSF (an intrinsic growth factor for melanocyte) production may retard recovery from vitiligo by checking the proliferation of surviving melanocytes. A significant decrease in TNF-α and IFN-γ production may partially explain the reduced inflammatory reaction in vitiliginous lesions. That IgG-anti-MC stimulates an increase in IL-1β and IFN-γ production in controls suggests that IgG-anti-MC may play a role in melanocyte destruction mediated by monocytes

Proopiomelanocortin gene delivery induces apoptosis in melanoma through NADPH oxidase 4-mediated ROS generation

AbstractHypoxia in the tumor microenvironment triggers differential signaling pathways for tumor survival. In this study, we characterize the involvement of hypoxia and reactive oxygen species (ROS) generation in the antineoplastic mechanism of proopiomelanocortin (POMC) gene delivery in a mouse B16-F10 melanoma model in vivo and in vitro. Histological analysis revealed increased TUNEL-positive cells and enhanced hypoxic activities in melanoma treated with adenovirus encoding POMC (Ad-POMC) but not control vector. Because the apoptotic cells were detected mainly in regions distant from blood vessels, it was hypothesized that POMC therapy might render melanoma cells vulnerable to hypoxic insult. Using a hypoxic chamber or cobalt chloride (CoCl2), we showed that POMC gene delivery elicited apoptosis and caspase-3 activation in cultured B16-F10 cells only under hypoxic conditions. The apoptosis induced by POMC gene delivery was associated with elevated ROS generation in vitro and in vivo. Blocking ROS generation using the antioxidant N-acetyl-l-cysteine abolished the apoptosis and caspase-3 activities induced by POMC gene delivery and hypoxia. We further showed that POMC-derived melanocortins, including α-MSH, β-MSH, and ACTH, but not γ-MSH, contributed to POMC-induced apoptosis and ROS generation during hypoxia. To elucidate the source of ROS generation, application of the NADPH oxidase inhibitor diphenyleneiodonium attenuated α-MSH-induced apoptosis and ROS generation, implicating the proapoptotic role of NADPH oxidase in POMC action. Of the NADPH oxidase isoforms, only Nox4 was expressed in B16-F10 cells, and Nox4 was also elevated in Ad-POMC-treated melanoma tissues. Silencing Nox4 gene expression with Nox4 siRNA suppressed the stimulatory effect of α-MSH-induced ROS generation and cell apoptosis during hypoxia. In summary, we demonstrate that POMC gene delivery suppressed melanoma growth by inducing apoptosis, which was at least partly dependent on Nox4 upregulation

Measuring Technical Efficiency and Returns to Scale in Taiwan’s Baking Industry―A Case Study of the 85 °C Company

[[abstract]]Under an intense internationally competitive business environment, it is important to understand the production efficiency of the baking industry, where efficient management is becoming increasingly important to ensure the sustainable development of the company. Thus, this study uses data envelopment analysis (DEA) to appraise the performance of a well-known baking company (85 °C) and uses input and output constructs to measure its technical efficiency and scale efficiency scores to understand the major reasons for efficiency losses from 2011 to 2016. The empirical results indicate that low technical efficiency is the major reason for lower pure technical efficiency, since the scale efficiency is higher than pure technical efficiency. This means 85 °C is still improving overall operating efficiency and space efficiency. Moreover, the results also show that the III-generation operations style is more technically efficient and pure-technically efficient compared to those of I-generation and II-generation. Furthermore, the company’s financial performance is dependent upon the producer’s ability to stay on the production frontier due to the result of a positive relationship between return on assets (ROA) and technical efficiency. Last but not least, this study shows that 85 °C can gain higher performance and efficiency by enhancing technical efficiency and reinforcing strategic alignments with business goals.[[notice]]補正完

Productivity Change and Decomposition in Taiwan Bakery Enterprise―Evidence from 85 °C Company

[[abstract]]In recent years, the bakery market has grown rapidly. Alongside its growth and fast change, it is very important to comprehend the productivity change of the bakery industry. Nowadays, effective management is more and more important to ensure the sustainable development of enterprises. Thus, productivity change of 22 self-owned stores of a famous bakery company (85 °C) from 2011 to 2016 was quantitatively analyzed and evaluated by adopting Malmquist index model in this study. Based on the Malmquist index model, the overall mean for total productivity change of 85 °C increased slightly from 2011 to 2016, and the productivity change was easily affected by technical progress. Moreover, the results also show that the north-district self-owned stores (which are located in subtropical climate) have the worst technical progress and total factor productivity change during 2011–2016 period by adopting the non-parametric Kruskal–Wallis and Dunn post-hoc test.[[notice]]補正完

REG3A overexpression functions as a negative predictive and prognostic biomarker in rectal cancer patients receiving CCRT

Background. Concurrent chemoradiotherapy (CCRT) is suggested before resection surgery in the control of rectal cancer. Unfortunately, treatment outcomes are widely variable and highly patientspecific. Notably, rectal cancer patients with distant metastasis generally have a much lower survival rate. Accordingly, a better understanding of the genetic background of patient cohorts can aid in predicting CCRT efficacy and clinical outcomes for rectal cancer before distant metastasis. Methods. A published transcriptome dataset (GSE35452) (n=46) was utilized to distinguish prospective genes concerning the response to CCRT. We recruited 172 rectal cancer patients, and the samples were collected during surgical resection after CCRT. Immunohistochemical (IHC) staining was performed to evaluate the expression level of regenerating family member 3 alpha (REG3A). Pearson's chi-squared test appraised the relevance of REG3A protein expression to clinicopathological parameters. The Kaplan-Meier method was utilized to generate survival curves, and the log-rank test was performed to compare the survival distributions between two given groups. Results. Employing a transcriptome dataset (GSE35452) and focusing on the inflammatory response (GO: 0006954), we recognized that REG3A is the most significantly upregulated gene among CCRT nonresponders (log2 ratio=1.2472, p=0.0079). Following IHC validation, high immunoexpression of REG3A was considerably linked to advanced post-CCRT tumor status (p<0.001), post-CCRT lymph node metastasis (p=0.042), vascular invasion (p=0.028), and low-grade tumor regression (p=0.009). In the multivariate analysis, high immunoexpression of REG3A was independently correlated with poor disease-specific survival (DSS) (p=0.004) and metastasis-free survival (MeFS) (p=0.045). The results of the bioinformatic analysis also supported the idea that REG3A overexpression is implicated in rectal carcinogenesis. Conclusion. In the current study, we demonstrated that REG3A overexpression is correlated with poor CCRT effectiveness and inferior patient survival in rectal cancer. The predictive and prognostic utility of REG3A expression may direct patient stratification and decisionmaking more accurately for those patients

Aberrant Sensory Gating of the Primary Somatosensory Cortex Contributes to the Motor Circuit Dysfunction in Paroxysmal Kinesigenic Dyskinesia

Paroxysmal kinesigenic dyskinesia (PKD) is conventionally regarded as a movement disorder (MD) and characterized by episodic hyperkinesia by sudden movements. However, patients of PKD often have sensory aura and respond excellently to antiepileptic agents. PRRT2 mutations, the most common genetic etiology of PKD, could cause epilepsy syndromes as well. Standing in the twilight zone between MDs and epilepsy, the pathogenesis of PKD is unclear. Gamma oscillations arise from the inhibitory interneurons which are crucial in the thalamocortical circuits. The role of synchronized gamma oscillations in sensory gating is an important mechanism of automatic cortical inhibition. The patterns of gamma oscillations have been used to characterize neurophysiological features of many neurological diseases, including epilepsy and MDs. This study was aimed to investigate the features of gamma synchronizations in PKD. In the paired-pulse electrical-stimulation task, we recorded the magnetoencephalographic data with distributed source modeling and time-frequency analysis in 19 patients of newly-diagnosed PKD without receiving pharmacotherapy and 18 healthy controls. In combination with the magnetic resonance imaging, the source of gamma oscillations was localized in the primary somatosensory cortex. Somatosensory evoked fields of PKD patients had a reduced peak frequency (p &lt; 0.001 for the first and the second response) and a prolonged peak latency (the first response p = 0.02, the second response p = 0.002), indicating the synchronization of gamma oscillation is significantly attenuated. The power ratio between two responses was much higher in the PKD group (p = 0.013), indicating the incompetence of activity suppression. Aberrant gamma synchronizations revealed the defective sensory gating of the somatosensory area contributes the pathogenesis of PKD. Our findings documented disinhibited cortical function is a pathomechanism common to PKD and epilepsy, thus rationalized the clinical overlaps of these two diseases and the therapeutic effect of antiepileptic agents for PKD. There is a greater reduction of the peak gamma frequency in PRRT2-related PKD than the non-PRRT PKD group (p = 0.028 for the first response, p = 0.004 for the second response). Loss-of-function PRRT2 mutations could lead to synaptic dysfunction. The disinhibiton change on neurophysiology reflected the impacts of PRRT2 mutations on human neurophysiology