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To address the inter-hospital hierarchical allocation and scheduling problems, this research used the pooling resource concept to allocate medical staff among hospital branches as well as determine their monthly schedules. This study proposed a two-stage strategy. The first stage proposed three heuristic algorithms—HRA1 (human resource allocation based on the hospital's size), HRA2 (human resource allocation based on the average allocation), and HRA3 (human resource allocation based on the severity of penalties)—for medical staff allocation. The second stage used the improved particle swarm optimization (PSO) algorithm to schedule the medical staff within a reasonable time. Based on the numerical results, HRA3 was superior to HRA1 and HRA2. Furthermore, the analysis of two scenarios—varying the sizes of hospital branches (Scenario 1) and varying the total number of medical staff (Scenario 2)—showed that, when the sizes of hospital branches varied (Scenario 1), HRA3 was superior to HRA1 and HRA2 whereas, when the sizes were given (Scenario 2), the lowest number of medical staff possible was approximately 60. The findings of this research will help hospital managers make decisions concerning the allocation and scheduling of medical staff.

Background Nasal colonization of Staphylococcus aureus is a risk factor for the pathogen transmission and the development of infections. Limited information is available on the prevalence and molecular characteristics of S. aureus colonization in pediatric intensive care unit (ICU) patients. Methods A cross-sectional, island-wide study was conducted in 2011. Nasal swabs were collected from pediatric ICU patients at six tertiary hospitals in Taiwan. Results Of 114 patients enrolled in total, nasal colonization of S. arueus was detected in 30 (26.3%) of them, among whom 20 (17.5%) with methicillin-resistant S. arueus (MRSA). The ST59/SCCmec IV and V clones were most common and accounted for 45% of MRSA isolates, followed by ST239/SCCmec III (25%) and ST45/SCCmec IV (20%) clones. Three ST59 MRSA isolates carried the Panton-Valentine Leukocidin genes. Conclusions The results indicated a high prevalence of S. arueus and MRSA nasal colonization among pediatric ICU patients in Taiwan. Identification of epidemic clones warrants the implement of infection control measures to reduce colonization and prevent the dissemination of MRSA in hospitals.

Summary Pathogen-derived lipopolysaccharide (LPS) and cytokine tumor necrosis factor (TNF) activate NFκB with distinct duration dynamics, but how immune response genes decode NFκB duration to produce stimulus-specific expression remains unclear. Here, detailed transcriptomic profiling of combinatorial and temporal control mutants identified 81 genes that depend on stimulus-specific NFκB duration for their stimulus-specificity. Combining quantitative experimentation with mathematical modeling, we found that for some genes a long mRNA half-life allowed effective decoding, but for many genes this was insufficient to account for the data; instead, we found that chromatin mechanisms, such as a slow transition rate between inactive and RelA-bound enhancer states, could also decode NFκB dynamics. Chromatin-mediated decoding is favored by genes acting as immune effectors (e.g., tissue remodelers and T cell recruiters) rather than immune regulators (e.g., signaling proteins and monocyte recruiters). Overall, our results delineate two gene regulatory strategies that decode stimulus-specific NFκB dynamics and determine distinct biological functions.

Prodigiosin (PG), a red tripyrrole pigment, belongs to a member of the prodiginine family and is normally secreted by various sources including Serratia marcescens and other Gram-negative bacteria. The studies of PG have received innovative devotion as a result of reported antimicrobial, larvicidal and anti-nematoid immunomodulation and antitumor properties, owing to its antibiotic and cytotoxic activities. This review provides a comprehensive summary of research undertaken toward the isolation and structural elucidation of the prodiginine family of natural products. Additionally, the current evidence-based understanding of the biological activities and medicinal potential of PG is employed to determine the efficacy, with some reports of information related to pharmacokinetics, pharmacodynamics and toxicology.

Background Obesity and its associated conditions, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are a particular worldwide health problem at present. Momordica cochinchinensis fruit is consumed widely in Southeast Asia. However, whether it has functional effects on fat-induced metabolic dysfunction and gut microbiota remains unclear. This study was conducted to determine how Momordica cochinchinensis aril (MCA) affects obesity, nonalcoholic fatty liver, insulin resistance and gut microbiota in diet-induced obese mice.Methods Wild type male mice at age of 5 weeks received four different kinds of diets: a normal diet, high-fat diet (HFD), or HFD supplemented with 1% or 3% (wt:wt) lyophilized MCA for 10 weeks. Body weight, adipose tissue and liver weight, serum biochemical parameters, glucose tolerance and liver lipids were measured. Gut microbial composition was analyzed.Results MCA protected the mice against high-fat diet (HFD)-induced body weight gain, hyperlipidemia and hyperglycemia, compared with mice that were not treated. MCA inhibited the expansion of adipose tissue and adipocyte hypertrophy. In addition, the insulin sensitivity-associated index that evaluates insulin function was also significantly restored. MCA also regulated the secretion of adipokines in HFD-induced obese mice. Moreover, hepatic fat accumulation and liver inflammation were reduced, which suggested that fatty liver was prevented by MCA. Furthermore, MCA supplementation suppressed hepatic lipid accumulation by activation of AMPK and PPAR-alpha signaling pathway in the human fatty liver HuS-E/2 cell model. Supplementation with MCA resulted in microbiota populations changed significantly.Conclusion Our data indicate that dietary MCA is involved in the prevention of HFD-induced adiposity, insulin resistance and nonalcoholic fatty liver disease and altered the microbial contents of the gut and modulated microbial dysbiosis in the host.

Additional file 1. STROBE Statement—Checklist of items that should be included in reports of cross-sectional studies

In the current study, an NMR spectroscopic pattern-based procedure for probing scalarane derivatives was performed and four new 24-homoscalaranes, lendenfeldaranes A&ndash, D (1&ndash, 4), along with three known compounds, 12&alpha, acetoxy-22-hydroxy-24-methyl-24-oxoscalar-16-en- 25-al (5), felixin F (6), and 24-methyl-12,24,25-trioxoscalar-16-en-22-oic acid (7) were isolated from the sponge Lendenfeldia sp. The structures of scalaranes 1&ndash, 7 were elucidated on the basis of spectroscopic analysis. Scalaranes 1&ndash, 7 were further evaluated for their cytotoxicity toward a series of human cancer cell lines and the results suggested that 5 and 7 dominated in the anti- proliferative activity of the extract. The 18-aldehyde functionality was found to play a key role in their activity.

Nonalcoholic fatty liver disease (NAFLD) is common worldwide and closely associated with metabolic dysfunction. NAFLD leads to a higher risk of development of severe liver diseases, such as nonalcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). To date, no pharmacotherapy targeting NAFLD has received general approval. Adlay is a plant that has been used as traditional herbal medicine in Asia and is a promising candidate to solve this global issue. We have established a mouse model of NAFLD by feeding a high-fat diet (HFD) for 10 weeks. Here, ethanolic or water extracts of adlay seed (ASE and ASW, respectively), mixed with HFD, were fed to the mice for 10 weeks. The ASE and ASW treatment ameliorated hyperglycemia and improved the glucose tolerance and insulin resistance in the HFD mice. Hyperlipidemia in HFD mice was prevented by the ASE and ASW diet. In addition, the ASE and ASW supplementation attenuated hepatic steatosis and inflammation, improved liver function, and caused no harm to the kidneys. Moreover, the mechanism of the effect of ASE and ASW on inhibiting hepatic lipogenesis and inducing fatty acid β-oxidation was certified by the simulated human fatty liver cell model. Our study showed the regulatory potential of the extracts of adlay seeds for alleviating NAFLD, as well as related liver and metabolic diseases.

Two color laser pulses are used to form an air plasma and generate broadband infrared radiation suitable as a seed for backward Raman amplification of CO2 laser pulses. Broadband radiation in the atmospheric window from 8-14 microns is observed. The infrared radiation is characterized using a long wavelength grating spectrometer specially designed to accept an ionizing laser filament at its input plane. The LWIR yield is greatly enhanced by chirping the drive pulse. Unidirectional pulse propagation simulations suggest that this is due in part to the dependence of the nonlinear refractive index on the pulse duration., Comment: 7 pages, 8 figures

This study investigates patient appointment scheduling and examination room assignment problems involving patients who undergo ultrasound examination with considerations of multiple examination rooms, multiple types of patients, multiple body parts to be examined, and special restrictions. Following are the recommended time intervals based on the findings of three scenarios in this study: In Scenario 1, the time interval recommended for patients’ arrival at the radiology department on the day of the examination is 18 min. In Scenario 2, it is best to assign patients to examination rooms based on weighted cumulative examination points. In Scenario 3, we recommend that three outpatients come to the radiology department every 18 min to undergo ultrasound examinations; the number of inpatients and emergency patients arriving for ultrasound examination is consistent with the original time interval distribution. Simulation optimization may provide solutions to the problems of appointment scheduling and examination room assignment problems to balance the workload of radiological technologists, maintain high equipment utilization rates, and reduce waiting times for patients undergoing ultrasound examination.

Summary: Background: This study compared the operative outcomes of percutaneous nephrolithotomy in elderly patients with different comorbidity status and different stone complexity. Methods: A retrospective review of medical records was performed of 113 patients aged 65 years or older with large renal stones who underwent percutaneous nephrolithotomy between 2007 and 2016. Patients were stratified by comorbidity status using the Charlson comorbidity index and by stone complexity using the Guy's score. The demographic data, stone parameters, stone-free rates, and complication rates were compared. Factors associated with complications and stone free rate were analyzed using logistic regression. Results: Patients with higher Charlson comorbidity index were older, used more anticoagulant medications, had higher ASA score, had longer operative times, and had longer hospital stay. Patients with higher Guy's score had higher stone burden, longer operative times, and a more significant decrease in GFR postoperatively. Logistic regression found that pre-operative pyuria and higher Charlson comorbidity index increased the risk of overall complications, and higher stone burden and higher Guy's score were associated with decreased stone free rates. Conclusion: This study supported the use of the Charlson comorbidity index in predicting post-operative complications and the Guy's score in predicting stone-free status in elderly patients with large renal stones undergoing percutaneous nephrolithotomy. Keywords: elderly, percutaneous nephrolithotomy, comorbidity, treatment outcome, complications

A new, physically motivated, basis set expansion method for solving quantum eigenvalue problems with competing interaction potentials is presented. In contrast to the usual dissection of the potential energy into unperturbed and perturbing terms, we divide the kinetic energy into partial terms by modifying the mass factor. The partition scheme results in partial kinetic energies with their effective mass factors. By distributing each partial kinetic energy to a respective potential energy to form a subsystem, the total Hamiltonian is written as the sum of subsystem Hamiltonians. Using a linear combination of the subsystem wave-functions to represent the system wave-function we obtain a set of coupled equations for the expansion coefficients, by solving these energies and wave-functions can be obtained. We demonstrate the solution scheme with a standard model system: a confined harmonic oscillator in a one-dimensional box. With only a few (less than ten) basis functions from each subsystem, we can reproduce the exact solutions very accurately, thus showing the applicability of this method.

Historically, the assessment of nonverbal behaviors such as facial expressions and gestures have relied heavily on observations made with the naked eye. Previous studies have shown that the manual analysis of micro-expressions can be both arduous and time consuming, and often suffers from a low level of reliability. However, new technology may bring forth new opportunities to refine this type of investigation. This research applied three feature extraction algorithms from the field of computer science to assist in measuring subtle dynamic movements in the human face. The Constraint Local Model (CLM) algorithm was employed to detect the faces and track the feature points; coordinates changing position across the frame indicated local facial activity. Based on these features points, facial regions of interest (ROIs) were identified for further analysis by Local Binary Pattern (LBP) and Optical Flow (OF). The LBP algorithm was used to extract texture information from the ROIs and measure correlations among frames; OF was used to analyze facial actions based on the main direction and distance of movement. The results of the three methods were then compared with manual coding. The proposed methods, especially OF, proved to be both robust and reliable.

Copper acetate mediated (4 + 2) annulation of sulfonylacetylenes with salicylic acids provides sulfonyl chromen-4-ones in the presence of benzotriazol-1-yloxy tri(dimethylamino)phosphonium hexafluorophosphate (BOP, Castro’s reagent) and 4-dimethylaminopyridine (DMAP) in MeNO2 at reflux for 3 h. The uses of various metal complexes and activating reagents are investigated for facile and efficient transformation. A plausible mechanism is proposed.

Micro-expression recognition is influenced by emotional contexts at the behavioral level. It is found that the recognition for micro-expressions is poorer following a negative context compared to the recognition following a neutral context. However, it remains unclear whether the modulation takes place in the early or later stage of the processing of micro-expressions as reflected in event-related potentials (ERPs). Using synthesized micro-expressions in this study, we investigated how emotional context modulates the ERP components that are elicited by micro-expressions. We observed that, compared to neutral contexts, negative and positive contexts elicited more positive amplitude trends for processing the subsequent target micro-expressions, and more positive P1 and N170 effects were elicited by target micro-expressions following negative and positive contexts compared to those following neutral contexts. Moreover, there were larger P1 effects elicited by the target micro-expressions when the context and target expressions were incongruent compared to when they were congruent. Our findings provide new ERP evidence to indicate that emotional contexts modulate micro-expression processing, and that the modulation of emotional contexts takes place at the early stage of facial-expression processing.

Penile calciphylaxis is a rare cause of penile gangrene that presents in patients with end-stage renal disease. The rates of comorbidity and mortality of penile calciphylaxis are extremely high. Unlike other penile gangrene, such as Fournier’s gangrene, the benefit of aggressive surgical therapy is controversial. Here we present a case of penile calciphylaxis in a 43-year-old man with end-stage renal disease on hemodialysis. He received total penectomy but died due to multisystem complications 2 weeks after surgery. We review the literature on the management options and outcomes in patients with penile calciphylaxis.

We present a general formulation of our previously developed kinetic energy partition (KEP) method for solving many-bodySchrodinger equations. In atomic physics, as well as in general molecular and solid state physics, solving many-electronSchrodinger equations is a very challenging task, often called Dirac’s challenge. The central problem is how to properly handle the electron–electron Coulomb repulsion interactions. Using the KEP solution scheme, in addition to dividing the kinetic energy into partial terms, the electron–electron Coulomb interaction is also separated into parts to be associated with a “negative mass” kinetic energy term. Therefore, the full Hamiltonian can be expressed as a simple sum of subsystem Hamiltonians, each representing an effective one-body problem. Using a Hartree-like product in constructing the wave-function, we achieve fast convergence in the calculations of the ground state energies. First, the model Moshinsky atoms are used to illustrate the solution procedure. We then apply this new KEP method to harmonium atoms and obtain precise energies with an error less than 5 % using only two basis functions from each subsystem. It is thus very promising that this methodology, when further extended, can be useful for general many-body systems.

Industri pariwisata dan perhotelan di Bali merupakan salah satu sektor yang terdampak pandemic COVID-19 hingga mengalami penurunan dari 528.883 kedatangan sebelum pandemi hingga hanya 47 kedatangan dalam 6 bulan. Hal ini tentunya mendorong penyedia bisnis untuk terus bertahan dan beradaptasi serta terus mencari cara untuk menarik minat turis untuk menggunakan jasanya. Hotel bintang lima di Bali merupakan kategori hotel dengan kamar terbanyak dan memenangkan penghargaan-penghargaan internasional mengenai kemewahannya, dimana jasa dan fasilitas yang ditawarkan tentunya harus sebanding dengan harga yang harus dibayarkan pelanggan. Kualitas layanan menjadi salah satu faktor yang mempengaruhi kepuasan pelanggan, dimana kepuasan pelanggan ini pada era perkembangan teknologi dan Big Data dituliskan dalam platform penyedia akomodasi online . Dengan jumlah ulasan yang jumlah dan variasinya sangat besar, Text Mining dapat dipilih menjadi solusi untuk mengumpulkan data ulasan tersebut dengan tujuan untuk mengekstraksi data dan mencari tahu atribut hotel yang memiliki frekuensi terbesar dalam ulasan pelanggan hotel bintang lima di Bali. Dengan adanya metode ini penyedia jasa dapat terbantu dalam mengidentifikasi kebutuhan, proses perencanaan, dan dalam rangka mengembangkan jasa serta kualitas layanan guna mencapai kepuasan pelanggan.

Androgens have been shown to have a beneficial effect on brain injury and lower reactive astrocyte expression after TBI. Androgen receptors (ARs) are known to mediate the neuroprotective effects of androgens. However, whether ARs play a crucial role in TBI remains unknown. In this study, we investigated the role of ARs in TBI pathophysiology, using AR knockout (ARKO) mice. We used the controlled cortical impact model to produce primary and mechanical brain injuries and assessed motor function and brain-lesion volume. In addition, the AR knockout effects on necrosis and autophagy were evaluated after TBI. AR knockout significantly increased TBI-induced expression of the necrosis marker alpha-II-spectrin breakdown product 150 and astrogliosis marker glial fibrillary acidic protein. In addition, the TBI-induced astrogliosis increase in ARKO mice lasted for three weeks after a TBI. The autophagy marker Beclin-1 was also enhanced in ARKO mice compared with wild-type mice after TBI. Our results also indicated that ARKO mice showed a more unsatisfactory performance than wild-type mice in a motor function test following TBI. Further, they were observed to have more severe lesions than wild-type mice after injury. These findings strongly suggest that ARs play a role in TBI.

A new natural indole, vibrindole B (1), together with known analogs, vibrindole A (2), trisindoline (3), norharmane (4), and 3-(hydroxyacetyl)indole (5), produced by the bacterium Pseudovibrio denitrificans P81, were isolated from a sponge, Aaptos species. The structures of indoles 1 to 5 were established by spectroscopic methods. The proposed biosynthetic pathway of 1 to 5 is also discussed, starting from tryptophan. Moreover, indoles 1 to 3 were found to exhibit cytotoxicity toward T24 tumor cells with IC50 values of 1.71 ± 0.11, 4.53 ± 0.14, and 2.26 ± 0.26 µM, respectively.

Composite photocatalysts comprising graphitic carbon nitride (g-C3N4) and graphene materials were synthesized and evaluated in the photocatalysis of bisphenol A (BPA) with a focus on elucidating the reaction mechanism. Embedding reduced graphene oxide (rGO) to g-C3N4 significantly accelerated the photocatalysis rate of BPA by three folds under visible light irradiation at neutral pH. We showed that rGO synthesized in intimate contact with g-C3N4 increased the surface areas and electrical conductivity of the g-C3N4 composites and promoted the electron-hole pair separation. The BPA photodegradation mechanism involved selective oxidants as superoxide (O2•−) and singlet oxygen (1O2) that were formed through one-electron reduction of O2 and the unique oxidation of O2•− by photogenerated hole (h+), respectively. The synthesized photocatalyst exhibited superior visible light photoreactivity to that of N-doped P25 TiO2, good photo-stability and reuse potential, and was operative in complex wastewater. rGO embedded g-C3N4 achieved good photomineralization of BPA at 80% in 4 h compared to 40% of bare g-C3N4. This study sheds light on the photocatalysis mechanism of BPA with a metal-free, promising rGO/g-C3N4 photocatalyst.

Most cancer cases are closely related to many risk factors such as environment and diets. Carcinogenesis may also be controlled by epigenetic regulation. Salvia miltiorrhiza Bunge (Danshen) is a common Chinese herbal medicine, and it has been reported that it has anti-cancer, anti-inflammatory, anti-coagulant, and anti-thrombotic activities. In this study, we studied the effect and epigenetic mechanisms of cryptotanshinone (CTS) and dihydrotanshinone (DHTS), the major active ingredients in Danshen, against human colorectal cancer HCT116 cells. The results showed that CTS and DHTS suppressed the proliferation of HCT116 cells for 72-hour treatment and induced mRNA and protein expressions of p21 and DLEC1. Pro-apoptosis proteins such as PARP, caspase-3, and caspase-9 are cleaved and activated in HCT116 cells treating CTS and DHTS. Moreover, CTS and DHTS also increased the protein levels of epigenetics regulating enzymes, including histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) in HCT116 cells. Therefore, it is suggested that CTS and DHTS may affect tumor suppressor genes, such as p21 and DLEC1, by regulating epigenetic mechanisms, which induce apoptosis of colorectal cancer HCT116 cells. Citation Format: Zheng-Yuan Su, Yu-Hsin Chen Chen, Tien-Yuan Wu. Cryptotanshinone and dihydrotanshinone epigenetically suppress human colorectal cancer cell growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2613.

Deception has been reported to be influenced by task-relevant emotional information from an external stimulus. However, it remains unclear how task-irrelevant emotional information would influence deception. In the present study, facial expressions of different valence and emotion intensity were presented to participants, where they were asked to make either truthful or deceptive gender judgments according to the preceding cues. We observed the influence of facial expression intensity upon individuals' cognitive cost of deceiving (mean difference of individuals' truthful and deceptive response times). Larger cost was observed for high intensity faces compared to low intensity faces. These results provided insights on how automatic attraction of attention evoked by task-irrelevant emotional information in facial expressions influenced individuals' cognitive cost of deceiving.

Two novel 16-membered tetraene marcolides, bafilomycins N (1) and O (2), along with two known analogues, JBIR-100 (3) and bafilomycin K (4) were produced from isolate GIC10-1, a Streptomyces sp. strain that was originally cloned from bacterial communities associated with marine sponge Theonella sp. The structures of new bafilomycins 1 and 2 were established by using spectroscopic methods and comparing the spectroscopic data with those of known related metabolites. Compounds 1 and 2 were proven to be the first 14-methylbafilomycins to be isolated. Cytotoxicity of these compounds toward various cancer cell lines also is described.

We generalize the recently developed kinetic energy partition (KEP) method for systems with two competing interactions to solve the quantum eigenvalue problems of a particle interacting with a number of harmonic-oscillator potentials. First, the original formulation of the KEP method is extended to the case with many interaction potentials. Second, we apply the method to the two and three harmonic-oscillators problems, respectively. Finally, the general N harmonic-oscillators system is considered and solved. We show that the KEP method can yield the exact solutions very accurately and efficiently.

In this work, we developed a concise synthetic route for the synthesis of polysubstituted naphthalenes starting from commercially available isovanillin and its derivatives. Reaction with styryl bromide via O-styrylation, Claisen rearrangement, ene reaction, and O-alkylation occurred in high yields. The key structures were confirmed by single-crystal X-ray diffraction.

The authors demonstrate the key role dataflows play in the optimization of energy efficiency for deep neural network (DNN) accelerators. By introducing a systematic approach to analyze the problem and a new dataflow, called Row-Stationary, which is up to 2.5 times more energy efficient than existing dataflows in processing a state-of-the-art DNN, this work provides guidelines for future DNN accelerator designs.

A facile route to the synthesis of γ-sulfonyl lactones 5 and β-sulfonyl styrenes 6 has been developed, achieving moderate to good yields via the (1) NaH mediated Michael addition of β-ketosulfones 3 and methyl acrylate in refluxing THF and (2) NaBH4 mediated stereoselective reduction/lactonization of δ-ketoesters 4 in boiling MeOH, or (3) boron trifluoride etherate mediated ring-opening of lactones 5 in MeOH at reflux.

Deep learning using convolutional neural networks (CNN) gives state-of-the-art accuracy on many computer vision tasks (e.g. object detection, recognition, segmentation). Convolutions account for over 90% of the processing in CNNs for both inference/testing and training, and fully convolutional networks are increasingly being used. To achieve state-of-the-art accuracy requires CNNs with not only a larger number of layers, but also millions of filters weights, and varying shapes (i.e. filter sizes, number of filters, number of channels) as shown in Fig. 14.5.1. For instance, AlexNet [1] uses 2.3 million weights (4.6MB of storage) and requires 666 million MACs per 227×227 image (13kMACs/pixel). VGG16 [2] uses 14.7 million weights (29.4MB of storage) and requires 15.3 billion MACs per 224×224 image (306kMACs/pixel). The large number of filter weights and channels results in substantial data movement, which consumes significant energy., United States. Defense Advanced Research Projects Agency (DARPA YFA grant N66001-14-1-4039), Intel Corporation, Massachusetts Institute of Technology. Center for Integrated Circuits and Systems

Hepatitis C virus (HCV) NS3 protein possesses protease and helicase activities and is considered an oncoprotein in virus-derived hepatocellular carcinoma. The NS3-associated oncogenesis has been studied but not fully understood. In this study, we have identified novel interactions of the NS3 protein with DNA repair factors, Werner syndrome protein (WRN) and Ku70, in both an HCV subgenomic replicon system and Huh7 cells expressing NS3. HCV NS3 protein inhibits WRN-mediated DNA repair and reduces the repair efficiency of nonhomologous end joining. It interferes with Ku70 recruitment to the double-strand break sites and alters the nuclear distribution of WRN-Ku repair complex. In addition, WRN is a substrate of the NS3/4A protease; the level of WRN protein is regulated by both the proteasome degradation pathway and HCV NS3/4A protease activity. The dual role of HCV NS3 and NS3/4A proteins in regulating the function and expression level of the WRN protein intensifies the effect of impairment on DNA repair. This may lead to an accumulation of DNA mutations and genome instability and, eventually, tumor development. IMPORTANCE HCV infection is a worldwide problem of public health and a major contributor to hepatocellular carcinoma. The single-stranded RNA virus with RNA-dependent RNA polymerase experiences a high error rate and develops strategies to escape the immune system and hepatocarcinogenesis. Studies have revealed the involvement of HCV proteins in the impairment of DNA repair. The present study aimed to further elucidate mechanisms by which the viral NS3 protein impairs the repair of DNA damage. Our results clearly indicate that HCV NS3/4A protease targets WRN for degradation, and, at the same time, diminishes the repair efficiency of nonhomologous end joining by interfering with the recruitment of Ku protein to the DNA double-strand break sites. The study describes a novel mechanism by which the NS3 protein influences DNA repair and provides new insight into the molecular mechanism of HCV pathogenesis.

Nonalcoholic fatty liver disease (NAFLD) is common worldwide and closely associated with metabolic dysfunction. NAFLD leads to a higher risk of development of severe liver diseases, such as nonalcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). To date, no pharmacotherapy targeting NAFLD has received general approval. Adlay is a plant that has been used as traditional herbal medicine in Asia and is a promising candidate to solve this global issue. We have established a mouse model of NAFLD by feeding a high-fat diet (HFD) for 10 weeks. Here, ethanolic or water extracts of adlay seed (ASE and ASW, respectively), mixed with HFD, were fed to the mice for 10 weeks. The ASE and ASW treatment ameliorated hyperglycemia and improved the glucose tolerance and insulin resistance in the HFD mice. Hyperlipidemia in HFD mice was prevented by the ASE and ASW diet. In addition, the ASE and ASW supplementation attenuated hepatic steatosis and inflammation, improved liver function, and caused no harm to the kidneys. Moreover, the mechanism of the effect of ASE and ASW on inhibiting hepatic lipogenesis and inducing fatty acid β-oxidation was certified by the simulated human fatty liver cell model. Our study showed the regulatory potential of the extracts of adlay seeds for alleviating NAFLD, as well as related liver and metabolic diseases.

Emerging AI-enabled applications such as augmented/virtual reality (AR/VR) leverage multiple deep neural network (DNN) models for sub-tasks such as object detection, hand tracking, and so on. Because of the diversity of the sub-tasks, the layers within and across the DNN models are highly heterogeneous in operation and shape. Such layer heterogeneity is a challenge for a fixed dataflow accelerator (FDA) that employs a fixed dataflow on a single accelerator substrate since each layer prefers different dataflows (computation order and parallelization) and tile sizes. Reconfigurable DNN accelerators (RDAs) have been proposed to adapt their dataflows to diverse layers to address the challenge. However, the dataflow flexibility in RDAs is enabled at the area and energy costs of expensive hardware structures (switches, controller, etc.) and per-layer reconfiguration. Alternatively, this work proposes a new class of accelerators, heterogeneous dataflow accelerators (HDAs), which deploys multiple sub-accelerators each supporting a different dataflow. HDAs enable coarser-grained dataflow flexibility than RDAs with higher energy efficiency and lower area cost comparable to FDAs. To exploit such benefits, hardware resource partitioning across sub-accelerators and layer execution schedule need to be carefully optimized. Therefore, we also present Herald, which co-optimizes hardware partitioning and layer execution schedule. Using Herald on a suite of AR/VR and MLPerf workloads, we identify a promising HDA architecture, Maelstrom, which demonstrates 65.3% lower latency and 5.0% lower energy than the best FDAs and 22.0% lower energy at the cost of 20.7% higher latency than a state-of-the-art RDA. The results suggest that HDA is an alternative class of Pareto-optimal accelerators to RDA with strength in energy, which can be a better choice than RDAs depending on the use cases., This paper is accepted at HPCA 2021

The v-raf murine sarcoma viral homolog B1 (BRAF) inhibitor drug vemurafenib (PLX4032) is used to treat melanoma, however, epidemiological evidence reveals that it could cause cutaneous keratoacanthomas and squamous cell carcinoma in cancer patients with the most prevalent HRASQ61L mutation. In a two-stage skin carcinogenesis mouse model, the skin papillomas induced by 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) (DT) resemble the lesions in BRAF inhibitor-treated patients. In this study, we investigated the bioactivity of Mentha aquatica var. Kenting Water Mint essential oil (KWM-EO) against PDV cells, mouse keratinocytes bearing HRASQ61L mutation, and its effect on inhibiting papilloma formation in a two-stage skin carcinogenesis mouse model with or without PLX4032 co-treatment. Our results revealed that KWM-EO effectively attenuated cell viability, colony formation, and the invasive and migratory abilities of PDV cells. Induction of G2/M cell-cycle arrest and apoptosis in PDV cells was also observed. KWM-EO treatment significantly decreased the formation of cutaneous papilloma further induced by PLX4032 in DT mice (DTP). Immunohistochemistry analyses showed overexpression of keratin14 and COX-2 in DT and DTP skin were profoundly suppressed by KWM-EO treatment. This study demonstrates that KWM-EO has chemopreventive effects against PLX4032-induced cutaneous side-effects in a DMBA/TPA-induced two-stage carcinogenesis model and will be worth further exploration for possible application in melanoma patients.

Matriptase plays important roles in epithelial integrity and function, which depend on its sorting to the basolateral surface of cells, where matriptase zymogen is converted to an active enzyme in order to act on its substrates. After activation, matriptase undergoes HAI-1-mediated inhibition, internalization, transcytosis, and secretion from the apical surface into the lumen. Matriptase is a mosaic protein with several distinct protein domains and motifs, which are a reflection of matriptase's complex cellular itinerary, life cycle, and the tight control of its enzymatic activity. While the molecular determinants for various matriptase regulatory events have been identified, the motif(s) required for translocation of human matriptase to the basolateral plasma membrane is unknown. The motif previously identified in rat matriptase is not conserved between the rodent and the primate. We, here, revisit the question for human matriptase through the use of a fusion protein containing a green fluorescent protein linked to the matriptase N-terminal fragment ending at Gly-149. A conserved seven amino acid motif EEGEVFL, which is similar to the monoleucine C-terminal to an acidic cluster motif involved in the basolateral targeting for some growth factors, has been shown to be required for matriptase translocation to the basolateral plasma membrane of polarized MDCK cells. Furthermore, time-lapse video microscopy showed that the motif appears to be required for entry into the correct transport vesicles, by which matriptase can undergo rapid trafficking and translocate to the plasma membrane. Our study reveals that the EEGEVFL motif is necessary, but may not be sufficient, for matriptase basolateral membrane targeting and serves as the basis for further research on its pathophysiological roles.