bluuebunny/crossref_metadata_2025 huggingface dataset:
HUBUNGAN KESEIMBANGAN DAN POWER OTOT TUNGKAI TERHADAP KEMAMPUAN TENDANGAN DOLLY CHAGI PADA ATLET UKM (UNIT KEGIATAN MAHASISWA) TAEKWONDO UNIVERSITAS BENGKULU
Authors: Ariansyah Arisman , Insanistyo Bayu , Sugiyanto Sugiyanto
Published: August 2019

Penelitian ini bertujuan untuk mengetahui hubungan antara keseimbangan dan power otot tungkai terhadap kemampuan tendangan Dollyo Chagi pada Atlet UKM (Unit Kegiatan Mahasiswa) Taekwondo Universitas Bengkulu. Penelitian ini merupakan penelitian korelasional dengan pendekatan cross-sectional. Sampel yang digunakan pada penelitian ini adalah mahasiswa UKM taekwondo UNIB sebanyak 18 orang. Peneliti menggunakan tekhnik pengumpulan data dengan cara melakukan tes dan pengukuran. Analisis data menggunakan analisis data korelasional. Berdasarkan hasil penelitian yang dilakukan diperoleh hasil, hubungan keseimbangan terhadap Kemampuan Tendangan Dollyo Chagi 0,62, Hubungan power otot tungkai terhadap kemampuan tendangan dollyo chagi sebesar 0,81 sedangkan hubungan antara keseimbangan dan power otot tungkai terhadap kemampuan tendangan dollyo chagi sebesar 0,82. Dengan demikian hasil penelitian menunjukan bahwa hubungan antara keseimbangan dan power otot tungkai terhadap kemampuan tendangan dollyo chagi memiliki hubungan yang signifikan.Kata kunci: Keseimbangan, power otot tungkai, tendangan dollyo chagi
A Business Process Analysis Methodology Based on Process Mining for Complaint Handling Service Processes
Authors: Wu Qiong , He Zhen , Wang Haijie , Wen Lijie , Yu Tongzhou
Published: August 2019

To improve the service quality of complaint handling service in a manufacturing company, it is key to analyze the business processes. Process mining is quite a useful approach to diagnose complaint handling service process problems, such as bottlenecks and deviations. However, the current business process analysis methodologies based on process mining mainly focus on operational process analysis and neglect other system level analysis. In this study, we introduce the method of Accimap from the discipline of accident analysis to analyze the diagnosis results of process mining. By creating a complaint handling service process management Accimap model, the process mining results analysis can be carried out across different system levels. A case study in a big manufacturing company in China is implemented to verify our approach. In the case study, 42 complaint handling process management factors are identified and the complaint handling process management Accimap model is created. The testing results by Rasmussen’s seven predictions in his risk management framework show that Accimap method presents a systematic approach to analyze the process diagnosis results based on process mining.
Measurement of Atmospheric Turbulence Characteristics by the Ultrasonic Anemometers and the Calibration Processes
Authors: Nosov Victor , Lukin Vladimir , Nosov Eugene , Torgaev Andrei , Bogushevich Aleksandr
Published: August 2019

In ultrasonic equipment (anemometers and thermometers), for the measurement of parameters of atmospheric turbulence, a standard algorithm that calculates parameters from temporary structural functions constructed on the registered data is usually used. The algorithm is based on the Kolmogorov–Obukhov law. The experience of using ultrasonic meters shows that such an approach can lead to significant errors. Therefore, an improved algorithm for calculating the parameters is developed, which allows more accurate estimation of the structural characteristics of turbulent fluctuations, with an error that is not more than 10%. The algorithm was used in the development of a new ultrasonic hardware-software complex, autonomous meteorological complex AMK-03-4, which differs from similar measuring instruments of turbulent atmosphere parameters by the presence of four identical ultrasonic anemometers. The design of the complex allows not only registration of the characteristics of turbulence, but also measurement of the statistical characteristics of the spatial derivatives of turbulent temperature fluctuations and orthogonal components of wind speed along each of the axes of the Cartesian coordinate system. This makes it possible to investigate the space–time structure of turbulent meteorological fields of the surface layer of the atmosphere for subsequent applications in the Monin–Obukhov similarity theory and to study turbulent coherent structures. The new measurement data of the spatial derivatives of temperature at stable stratification (at positive Monin–Obukhov parameters) were obtained, at which the behavior of the derivatives was been investigated earlier. In the most part of the interval of positive Monin–Obukhov parameters, the vertical derivative of the temperature is close to a constant value. This fact can be considered as a new significant result in similarity theory.
Anticancer Activity of Water-Soluble Olsalazine-PAMAM-Dendrimer-Salicylic Acid-Conjugates
Authors: Cortez-Maya Sandra , Pedro-Hernández Luis Daniel , Martínez-Klimova Elena , Ramírez-Ápan Teresa , Martínez-García Marcos
Published: August 2019

Improving the activity and selectivity profile of anticancer agents will require designing drug carrier systems that employ soluble macromolecules. Olsalazine-PAMAM-dendrimer-salicylic acid-conjugates with dendritic arms of different lengths have shown good stability regarding the chemical link between drug and spacer. In this study, the drug release was followed in vitro by ultraviolet (UV) studies. Evaluation of the cytotoxicity of the olsalazine-PAMAM-dendrimer-salicylic acid-conjugates employing a sulforhodamine B (SRB) assay in PC-3 (human prostatic adenocarcinoma) and MCF-7 (human mammary adenocarcinoma) cell lines demonstrated that conjugate 9 was more active as an antiproliferative agent than cisplatin, and no cytotoxicity towards the African green monkey kidney fibroblast (COS-7) cell line was observed in any of the conjugates synthesized in the present work.
Biological Significance of Tumor Heterogeneity in Esophageal Squamous Cell Carcinoma
Authors: Lin Lehang , Lin De-Chen
Published: August 2019

Esophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy, with hitherto dismal clinical outcome. Genomic analyses of patient samples reveal a complex heterogeneous landscape for ESCC, which presents in both intertumor and intratumor forms, manifests at both genomic and epigenomic levels, and contributes significantly to tumor evolution, drug resistance, and metastasis. Here, we review the important molecular characteristics underlying ESCC heterogeneity, with an emphasis on genomic aberrations and their functional contribution to cancer evolutionary trajectories. We further discuss how novel experimental tools, including single-cell sequencing and three-dimensional organoids, may advance our understanding of tumor heterogeneity. Lastly, we suggest that deciphering the mechanisms governing tumor heterogeneity holds the potential to developing precision therapeutics for ESCC patients.
A Tyrosine Kinase Expression Signature Predicts the Post-Operative Clinical Outcome in Triple Negative Breast Cancers
Authors: de Nonneville Alexandre , Finetti Pascal , Adelaide José , Lambaudie Éric , Viens Patrice , Gonçalves Anthony , Birnbaum Daniel , Mamessier Emilie , Bertucci François
Published: August 2019

Triple negative breast cancer (TNBC) represent 15% of breast cancers. Histoclinical features and marketed prognostic gene expression signatures (GES) failed to identify good- and poor-prognosis patients. Tyrosine kinases (TK) represent potential prognostic and/or therapeutic targets for TNBC. We sought to define a prognostic TK GES in a large series of TNBC. mRNA expression and histoclinical data of 6379 early BCs were collected from 16 datasets. We searched for a TK-based GES associated with disease-free survival (DFS) and tested its robustness in an independent validation set. A total of 1226 samples were TNBC. In the learning set of samples (N = 825), we identified a 13-TK GES associated with DFS. This GES was associated with cell proliferation and immune response. In multivariate analysis, it outperformed the previously published GESs and classical prognostic factors in the validation set (N = 401), in which the patients classified as “low-risk” had a 73% 5-year DFS versus 53% for “high-risk” patients (p = 1.85 × 10−3). The generation of 100,000 random 13-gene signatures by a resampling scheme showed the non-random nature of our classifier, which was also prognostic for overall survival in multivariate analysis. We identified a robust and non-random 13-TK GES that separated TNBC into subgroups of different prognosis. Clinical and functional validations are warranted.
Coordinated Expression of Ras Suppressor 1 (RSU-1) and Growth Differentiation Factor 15 (GDF15) Affects Glioma Cell Invasion
Authors: Louca Maria , Gkretsi Vasiliki , Stylianopoulos Triantafyllos
Published: August 2019

Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor due to its invasive phenotype. Ras suppressor 1 (RSU-1) is a cell-extracellular matrix adhesion protein and we recently found that it promotes cell invasion in aggressive cells and inhibits it in non-invasive. Growth differentiation factor-15 (GDF15) is known to be involved in actin cytoskeleton reorganization and metastasis. In this study, we used three brain cell lines (H4, SW1088 and A172) with increasing RSU-1 expression levels and invasive capacity and decreasing GDF15 levels to investigate the interplay between RSU-1 and GDF15 with regard to cell invasion. Four experimental approaches were used: (a) GDF15 treatment, (b) Rsu-1 silencing, (c) GDF15 silencing, and (d) combined GDF15 treatment and RSU-1 silencing. We found that the differential expression of RSU-1 and GDF15 in H4 and A172 cells leading to inhibition of cell invasion in H4 cells and promotion in A172 through respective changes in PINCH1, RhoA and MMP-13 expression. Interestingly SW1088, with intermediate RSU-1 and GDF15 expression, were not affected by any treatment. We conclude that there is a strong connection between RSU-1 and GDF15 in H4, SW1088 and A172 cells and the relative expression of these two proteins is fundamental in affecting their invasive fate.
N,O Chelating Ligands Construct Five-Coordinated Zn(II) Exclusive {Zn6} Clusters: Decomposition, Stepwise Assembly and Photoluminescence Study
Authors: Deng Qian-Jun , Chen Min , Chen Dong-Chu , Chen Chang-Ai
Published: August 2019

N-methylbenzimidazole-2-methanol (Hmbm) and Zn(NO3)2·6H2O were reacted in acetonitrile solvothermal at 80 °C for 48 h to obtain a six-nuclear Zn(II) cluster ([ZnII6(Hmbm)2(mbm)8(NO3)4]·12H2O·2CH3CN (Zn6)). Structural analysis indicated that Zn(II) in the above Zn6 clusters showed pentacoordinates. The metal centers Zn1 and Zn2 are both in the N2O3 coordination environment, and both show a triangular bipyramid configuration. Zn3 is in a NO4 coordination environment, which is also shown as a triangular bipyramid configuration. The ion source voltage of high-resolution electrospray ionization mass spectrometry (HRESI-MS) was further adjusted to bombard the Zn6 cluster, and seven major key intermediates were identified. Furthermore, we proposed that the gradual fragmentation mechanism is Zn6 → [ZnII6(mbm)8(NO3)3]+ → [ZnII5(mbm)7(NO3)2]+ → [ZnII4(mbm)6(NO3)]+ → [ZnII3(mbm)4(NO3)]+ → [ZnII2(mbm)3]+ → [ZnII2(mbm)2(OH)(H2O)2(DMSO)]+ → [ZnII(mbm)]+. In order to understand the gradual formation of Zn6 clusters, herein, we track the changes of species in the solution in different time periods by HRESI-MS. The nine key intermediates were identified and further combined with its gradual fragmentation mechanism. We proposed the gradual assembly mechanism of [ZnII(mbm)]+ → [ZnII(mbm)(Hmbm)]+ → [ZnII2(mbm)2(NO3)]+ → [ZnII2(mbm)3]+ → [ZnII3(mbm)4(NO3)]+ → [ZnII4(mbm)5(NO3)2]+ → [ZnII4(mbm)6(NO3)]+ → [ZnII5(mbm)7(NO3)2]+ → [ZnII6(mbm)8(NO3)3]+ → Zn6. To the best of our knowledge, this is the first time that a decomposition and assembly binding strategy has been used to resolve the stepwise formation of Zn(II) clusters. Photoluminescence measurements indicate that the cluster Zn6 exhibits a strong emission peak at 300 nm and an emission shoulder at 600 nm.
Immediate Effects of Hurricanes on a Diverse Coral/Mangrove Ecosystem in the U.S. Virgin Islands and the Potential for Recovery
Authors: Rogers Caroline
Published: August 2019

Hurricanes Irma and Maria, two powerful storms that hit the U.S. Virgin Islands less than 2 weeks apart in September 2017, caused extensive damage to the natural resources on St. John. Damage was particularly severe in a unique mangrove/coral ecosystem in three bays within Virgin Islands Coral Reef National Monument, a National Park Service marine protected area. Many Red Mangrove (Rhizophora mangle) trees were uprooted and tossed into the sea, and the prop roots of others were stripped of corals, sponges and other marine life. No other mangrove area in the Caribbean is known to have so many scleractinian corals (about 30 species before the storms). Although many corals were overturned or buried in rubble, colonies of most of the species, including four that are listed as threatened under the U.S. Endangered Species Act, survived. Recovery of this ecosystem will depend on Red Mangrove propagules becoming established and producing prop roots to support rich marine life along with a canopy to provide the shade that was critical to the biodiversity that was present before the storms. Unlike in many situations where major disturbances reduce coral cover, the substrate that must be restored for full recovery to occur is a living substrate—the prop roots of the mangroves. Larvae of corals and sponges will need to recruit on to the roots. Future storms could hinder this process.
Dactylogyrids (Platyhelminthes: Monogenoidea) Infecting the Gill Lamellae of Flatheads (Scorpaeniformes: Platycephalidae), with Proposal of Platycephalotrema n. gen. and Descriptions of New Species from Australia and Japan
Authors: Kritsky Delane , Nitta Masato
Published: August 2019

Platycephalotrema n. gen. (Dactylogyridae) is proposed for four new species and 5 previously described species parasitizing the gills of flatheads (Scorpaeniformes: Platycephalidae) as follows: Platycephalotrema ogawai n. sp. (type species) from Platycephalus sp. 1 (type host) and Platycephalus sp. 2, both of Nakabo & Kai (2013) (locally known as “Yoshino-gochi” and “Ma-gochi,” respectively) (Japan); Platycephalotrema austrinum n. sp. from Platycephalus endrachtensis Quoy & Gaimard (type host) and Platycephalus sp. (Australia); Platycephalotrema bassensis (Hughes, 1928) n. comb. from Platycephalus bassensis Cuvier (Australia); Platycephalotrema koppa n. sp. from Platycephalus fuscus Cuvier (Australia); Platycephalotrema macassarensis (Yamaguti, 1963) n. comb. from Platycephalus indicus (Linnaeus) (China, Macassar); Platycephalotrema mastix n. sp. from P. fuscus and P. endrachtensis (Australia); Platycephalotrema platycephali (Yin & Sproston, 1948) n. comb. from P. indicus (China) and P. fuscus (Australia); Platycephalotrema sinensis (Yamaguti, 1963) n. comb. from Cociella punctata (Cuvier) (China); Platycephalotrema thysanophrydis (Yamaguti, 1937) n. comb. from Inegocia japonica (Cuvier), Inegocia ochiaii Imamura, and Cociella crocodilus (Cuvier) (Japan, China). Other species requiring further study but potentially members of Platycephalotrema include Ancyrocephalus vesiculosus Murray, 1931, Haliotrema indicum Tripathi, 1957, Haliotrema swatowensis Yao, Wang, Xia, & Chen, 1998, and Haliotrema pteroisi Paperna, 1972. The primary features differentiating Platycephalotrema include species having: (1) tandem gonads (testis postgermarial); (2) two prostatic reservoirs, each emptying independently into the base of the male copulatory organ; (3) a dextral vaginal pore and large vaginal vestibule; (4) dorsal and ventral pairs of morphologically similar anchors; (5) a ventral bar with spatulate ends; (6) a dorsal bar with bifurcated ends, and (7) absence of an accessory piece. The new species are described, and P. thysanophrydis is redescribed based on newly collected and museum specimens.
Multi-Scale Heart Beat Entropy Measures for Mental Workload Assessment of Ambulant Users
Authors: Tiwari Abhishek , Albuquerque Isabela , Parent Mark , Gagnon Jean-François , Lafond Daniel , Tremblay Sébastien , H. Falk Tiago
Published: August 2019

Mental workload assessment is crucial in many real life applications which require constant attention and where imbalance of mental workload resources may cause safety hazards. As such, mental workload and its relationship with heart rate variability (HRV) have been well studied in the literature. However, the majority of the developed models have assumed individuals are not ambulant, thus bypassing the issue of movement-related electrocardiography (ECG) artifacts and changing heart beat dynamics due to physical activity. In this work, multi-scale features for mental workload assessment of ambulatory users is explored. ECG data was sampled from users while they performed different types and levels of physical activity while performing the multi-attribute test battery (MATB-II) task at varying difficulty levels. Proposed features are shown to outperform benchmark ones and further exhibit complementarity when used in combination. Indeed, results show gains over the benchmark HRV measures of 24.41 % in accuracy and of 27.97 % in F1 score can be achieved even at high activity levels.
Kernel Mixture Correntropy Conjugate Gradient Algorithm for Time Series Prediction
Authors: Xue Nan , Luo Xiong , Gao Yang , Wang Weiping , Wang Long , Huang Chao , Zhao Wenbing
Published: August 2019

Kernel adaptive filtering (KAF) is an effective nonlinear learning algorithm, which has been widely used in time series prediction. The traditional KAF is based on the stochastic gradient descent (SGD) method, which has slow convergence speed and low filtering accuracy. Hence, a kernel conjugate gradient (KCG) algorithm has been proposed with low computational complexity, while achieving comparable performance to some KAF algorithms, e.g., the kernel recursive least squares (KRLS). However, the robust learning performance is unsatisfactory, when using KCG. Meanwhile, correntropy as a local similarity measure defined in kernel space, can address large outliers in robust signal processing. On the basis of correntropy, the mixture correntropy is developed, which uses the mixture of two Gaussian functions as a kernel function to further improve the learning performance. Accordingly, this article proposes a novel KCG algorithm, named the kernel mixture correntropy conjugate gradient (KMCCG), with the help of the mixture correntropy criterion (MCC). The proposed algorithm has less computational complexity and can achieve better performance in non-Gaussian noise environments. To further control the growing radial basis function (RBF) network in this algorithm, we also use a simple sparsification criterion based on the angle between elements in the reproducing kernel Hilbert space (RKHS). The prediction simulation results on a synthetic chaotic time series and a real benchmark dataset show that the proposed algorithm can achieve better computational performance. In addition, the proposed algorithm is also successfully applied to the practical tasks of malware prediction in the field of malware analysis. The results demonstrate that our proposed algorithm not only has a short training time, but also can achieve high prediction accuracy.
The Efficiency of the Sustainable Development Policy for Energy Consumption under Environmental Law in Thailand: Adapting the SEM-VARIMAX Model
Authors: Sutthichaimethee Pruethsan , Naluang Sthianrapab
Published: August 2019

This research aims to predict the efficiency of the Sustainable Development Policy for Energy Consumption under Environmental Law in Thailand for the next 17 years (2020–2036) and analyze the relationships among causal factors by applying a structural equation modeling/vector autoregressive model with exogenous variables (SEM-VARIMAX Model). This model is effective for analyzing relationships among causal factors and optimizing future forecasting. It can be applied to contexts in different sectors, which distinguishes it from other previous models. Furthermore, this model ensures the absence of heteroskedasticity, multicollinearity, and autocorrelation. In fact, it meets all the standards of goodness of fit. Therefore, it is suitable for use as a tool for decision-making and planning long-term national strategies. With the implementation of the Sustainable Development Policy for Energy Consumption under Environmental Law ( S . D . E L ) , the forecast results derived from the SEM-VARIMAX Model indicate a continuously high change in energy consumption from 2020 to 2036the change exceeds the rate determined by the government. In addition, energy consumption is predicted to have an increased growth rate of up to 185.66% (2036/2020), which is about 397.08 ktoe (2036). The change is primarily influenced by a causal relationship that contains latent variables, namely, the economic factor ( E C O N ) , social factor ( S O C I ) , and environmental factor ( E N V I ) . The performance of the SEM-VARIMAX Model was tested, and the model produced a mean absolute percentage error (MAPE) of 1.06% and a root-mean-square error (RMSE) of 1.19%. A comparison of these results with those of other models, including the multiple linear regression model (MLR), back-propagation neural network (BP model), grey model, artificial neural natural model (ANN model), and the autoregressive integrated moving average model (ARIMA model), indicates that the SEM-VARIMAX model fits and is appropriate for long-term national policy formulation in various contexts in Thailand. This study’s results further indicate the low efficiency of Sustainable Development Policy for Energy Consumption under Environmental Law in Thailand. The predicted result for energy consumption in 2036 is greater than the government-established goal for consumption of no greater than 251.05 ktoe.
Numerical Modeling of CO2 Migration in Saline Aquifers of Selected Areas in the Upper Silesian Coal Basin in Poland
Authors: Urych Tomasz , Smoliński Adam
Published: August 2019

Determining the characteristics of the dynamic behavior of carbon dioxide in a rock mass is a stage in the process of assessing a potential CO2 storage reservoir. The aim of this study was to analyze the process of CO2 storage in saline aquifers of the selected regions of the Upper Silesian Coal Basin in Poland. The construction of dynamic simulation models was based on static models of real deposit structures developed on a regional scale. Different simulation variants of the CO2 storage process were adopted, varying in terms of injection efficiency and duration of individual simulation phases. The analysis examined the influence of the degree of hydrodynamic openness of the structure on the CO2 storage process, in each of the variants. The results of numerical simulations showed that among the three analyzed geological formations, the Dębowiec formation is the most prospective for potential CO2 storage and is characterized by the most favorable geological and hydrogeological parameters. In the best variant of the simulation, in which the safety of CO2 storage in the rock mass was taken into account, the total amount of CO2 injected in a single directional well was approximately 8.54 million Mg of CO2 during 25 years of injection.
The Presence and Consequences of Abortion Aversion in Scientific Research Related to Alcohol Use during Pregnancy
Authors: Roberts Sarah C.M.
Published: August 2019

Recent research has found that most U.S. state policies related to alcohol use during pregnancy adversely impact health. Other studies indicate that state policymaking around substance use in pregnancy—especially in the U.S.—appears to be influenced by an anti-abortion agenda rather than by public health motivations. This commentary explores the ways that scientists’ aversion to abortion appear to influence science and thus policymaking around alcohol and pregnancy. The three main ways abortion aversion shows up in the literature related to alcohol use during pregnancy include: (1) a shift from the recommendation of abortion for “severely chronic alcoholic women” to the non-acknowledgment of abortion as an outcome of an alcohol-exposed pregnancy; (2) the concern that recommendations of abstinence from alcohol use during pregnancy lead to terminations of otherwise wanted pregnancies; and (3) the presumption of abortion as a negative pregnancy outcome. Thus, abortion aversion appears to influence the science related to alcohol use during pregnancy, and thus policymaking—to the detriment of developing and adopting policies that reduce the harms from alcohol during pregnancy.
A Long Polymorphic GT Microsatellite within a Gene Promoter Mediates Non-Imprinted Allele-Specific DNA Methylation of a CpG Island in a Goldfish Inter-Strain Hybrid
Authors: Zheng Jianbo , Xu Haomang , Cao Huiwen
Published: August 2019

It is now widely accepted that allele-specific DNA methylation (ASM) commonly occurs at non-imprinted loci. Most of the non-imprinted ASM regions observed both within and outside of the CpG island show a strong correlation with DNA polymorphisms. However, what polymorphic cis-acting elements mediate non-imprinted ASM of the CpG island remains unclear. In this study, we investigated the impact of polymorphic GT microsatellites within the gene promoter on non-imprinted ASM of the local CpG island in goldfish. We generated various goldfish heterozygotes, in which the length of GT microsatellites or some non-repetitive sequences in the promoter of no tail alleles was different. By examining the methylation status of the downstream CpG island in these heterozygotes, we found that polymorphisms of a long GT microsatellite can lead to the ASM of the downstream CpG island during oogenesis and embryogenesis, polymorphisms of short GT microsatellites and non-repetitive sequences in the promoter exhibited no significant effect on the methylation of the CpG island. We also observed that the ASM of the CpG island was associated with allele-specific expression in heterozygous embryos. These results suggest that a long polymorphic GT microsatellite within a gene promoter mediates non-imprinted ASM of the local CpG island in a goldfish inter-strain hybrid.
Streptococcal Pyrogenic Exotoxin A-Stimulated Monocytes Mediate Regulatory T-Cell Accumulation through PD-L1 and Kynurenine
Authors: Giesbrecht Katharina , Förmer Sandra , Sähr Aline , Heeg Klaus , Hildebrand Dagmar
Published: August 2019

Bacterial superantigens (SAgs) are exotoxins that promote a fulminant activation of the immune system. The subsequent intense release of inflammatory cytokines often results in hypotension, shock, and organ failure with high mortality rates. In the current paradigm, the direct and simultaneous binding of SAgs with T-cell receptor (TCR)-bearing Vβ regions and conserved structures on major histocompatibility complex class II (MHC class II) on antigen-presenting cells (APCs) induces the activation of both cell types. However, by crosslinking MHC class II molecules, APCs can be activated by SAgs independently of T lymphocytes. Recently, we showed that streptococcal pyrogenic exotoxin A (SPEA) of Streptococcus pyogenes stimulates an immunogenic APC phenotype with upregulated costimulatory molecules and inflammatory cytokines. Additionally, we revealed that SPEA triggers immunosuppressive programs in monocytes that facilitate the accumulation of regulatory T cells (Tregs) in in vitro monocyte/CD4+ T-cell cocultures. Immunosuppressive factors include anti-inflammatory interleukin 10 (IL-10), co-inhibitory surface molecule programmed cell death 1 ligand 1 (PD-L1), and the inhibitory indoleamine 2,3-dioxygenase (IDO)/kynurenine effector system. In the present study, we investigated the underlying mechanism of SPEA-stimulated monocyte-mediated accumulation of Tregs. Blood-derived monocytes from healthy donors were stimulated with SPEA for 48 h (SPEA-monocytes). For the evaluation of SPEA-monocyte-mediated modulation of CD4+ T lymphocytes, SPEA was removed from the culture through extensive washing of cells before adding allogeneic CD3/CD28-activated T cells. Results: In coculture with allogeneic CD4+ T cells, SPEA-monocytes mediate apoptosis of CD4+Foxp3− lymphocytes and accumulation of CD4+Foxp3+ Tregs. PD-L1 and kynurenine are critically involved in the mediated cell death because blocking both factors diminished apoptosis and decreased the proportion of the CD25+/Foxp3+ Treg subpopulation significantly. Upregulation of PD-L1 and kynurenine as well as SPEA-monocyte-mediated effects on T cells depend on inflammatory IL-1β. Our study shows that monocytes activated by SPEA mediate apoptosis of CD4+Foxp3− T effector cells through PD-L1 and kynurenine. CD4+Foxp3+ T cells are resistant to apoptosis and accumulate in SPEA-monocyte/CD4+ T-cell coculture.
The Immune Landscape of Thyroid Cancer in the Context of Immune Checkpoint Inhibition
Authors: Varricchi Gilda , Loffredo Stefania , Marone Giancarlo , Modestino Luca , Fallahi Poupak , Ferrari Silvia Martina , de Paulis Amato , Antonelli Alessandro , Galdiero Maria Rosaria
Published: August 2019

Immune cells play critical roles in tumor prevention as well as initiation and progression. However, immune-resistant cancer cells can evade the immune system and proceed to form tumors. The normal microenvironment (immune cells, fibroblasts, blood and lymphatic vessels, and interstitial extracellular matrix (ECM)) maintains tissue homeostasis and prevents tumor initiation. Inflammatory mediators, reactive oxygen species, cytokines, and chemokines from an altered microenvironment promote tumor growth. During the last decade, thyroid cancer, the most frequent cancer of the endocrine system, has emerged as the fifth most incident cancer in the United States (USA), and its incidence is steadily growing. Inflammation has long been associated with thyroid cancer, raising critical questions about the role of immune cells in its pathogenesis. A plethora of immune cells and their mediators are present in the thyroid cancer ecosystem. Monoclonal antibodies (mAbs) targeting immune checkpoints, such as mAbs anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA-4) and anti-programmed cell death protein-1/programmed cell death ligand-1 (anti-PD-1/PD-L1), have revolutionized the treatment of many malignancies, but they induce thyroid dysfunction in up to 10% of patients, presumably by enhancing autoimmunity. Combination strategies involving immune checkpoint inhibitors (ICIs) with tyrosine kinase (TK) or serine/threonine protein kinase B-raf (BRAF) inhibitors are showing considerable promise in the treatment of advanced thyroid cancer. This review illustrates how different immune cells contribute to thyroid cancer development and the rationale for the antitumor effects of ICIs in combination with BRAF/TK inhibitors.
Influence of Unit Cell Size and Fiber Packing on the Transverse Tensile Response of Fiber Reinforced Composites
Authors: D’Mello Royan J. , Waas Anthony M.
Published: August 2019

Representative volume elements (RVEs) are commonly used to compute the effective elastic properties of solid media having repeating microstructure, such as fiber reinforced composites. However, for softening materials, an RVE could be problematic due to localization of deformation. Here, we address the effects of unit cell size and fiber packing on the transverse tensile response of fiber reinforced composites in the context of integrated computational materials engineering (ICME). Finite element computations for unit cells at the microscale are performed for different sizes of unit cells with random fiber packing that preserve a fixed fiber volume fraction—these unit cells are loaded in the transverse direction under tension. Salient features of the response are analyzed to understand the effects of fiber packing and unit cell size on the details of crack path, overall strength and also the shape of the stress-strain response before failure. Provision for damage accumulation/cracking in the matrix is made possible via the Bazant-Oh crack band model. The results suggest that the choice of unit cell size is more sensitive to strength and less sensitive to stiffness, when these properties are used as homogenized inputs to macro-scale models. Unit cells of smaller size exhibit higher strength and this strength converges to a plateau as the size of the unit cell increases. In this sense, since stiffness has also converged to a plateau with an increase in unit cell size, the converged unit cell size may be thought of as an RVE. Results in support of these insights are presented in this paper.
Influence of Different Pretreatments on the Structure and Hydrolysis Behavior of Bamboo: A Comparative Study
Authors: Qi Xuemin , Chu Jie , Jia Liangliang , Kumar Anuj
Published: August 2019

In the present study, three pretreatments of sodium hydroxide (NaOH), sulfuric acid (H2SO4), and glycerin were employed with bamboo fibers at two different temperatures of 117 °C and 135 °C, respectively. The chemical composition and structural characterization of the pretreated bamboo fibers were comparatively studied using spectroscopic and wet chemistry methods. Furthermore, the comparative hydrolysis behaviors of pretreated bamboo were studied due to the synergistic interaction between cellulases and xylanase. The NaOH treatment increased the holocellulose contents to 87.4%, and the mean diameter of the cellulose fibers decreased from 50 ± 5 µm (raw fiber bundles) to 5 ± 2 µm. The lignin content and the degree of cellulose polymerization both decreased, while the crystallinity index of cellulose and thermostability increased. The hydrolysis yields of NaOH pretreated bamboo at 135 °C increased from 84.2% to 98.1% after a supplement of 0.5 cellulose to 1 mg protein/g dry xylan. The NaOH pretreatment achieved optimal enzymatic digestibility, particularly at higher temperatures as indicated by the results.
A Different Approach to Estimate Temperature-Dependent Thermal Properties of Metallic Materials
Authors: Carollo Luís Felipe dos Santos , Lima e Silva Ana Lúcia Fernandes de , Lima e Silva Sandro Metrevelle Marcondes de
Published: August 2019

Thermal conductivity, λ, and volumetric heat capacity, ρcp, variables that depend on temperature were simultaneously estimated in a diverse technique applied to AISI 1045 and AISI 304 samples. Two distinctive intensities of heat flux were imposed to provide a more accurate simultaneous estimation in the same experiment. A constant heat flux was imposed on the upper surface of the sample while the temperature was measured on the opposite insulated surface. The sensitivity coefficients were analyzed to provide the thermal property estimation. The Broydon-Fletcher-Goldfarb-Shanno (BFGS) optimization technique was applied to minimize an objective function. The squared difference objective function of the numerical and experimental temperatures was defined considering the error generated by the contact resistance. The temperature was numerically calculated by using the finite difference method. In addition, the reliability of the results was assured by an uncertainty analysis. Results showing a difference lower than 7% were obtained for λ and ρcp, and the uncertainty values were above 5%.
Targeting Microbiota: What Do We Know about It at Present?
Authors: Derovs Aleksejs , Laivacuma Sniedze , Krumina Angelika
Published: August 2019

The human microbiota is a variety of different microorganisms. The composition of microbiota varies from host to host, and it changes during the lifetime. It is known that microbiome may be changed because of a diet, bacteriophages and different processes for example, such as inflammation. Like all other areas of medicine, there is a continuous growth in the area of microbiology. Different microbes can reside in all sites of a human body, even in locations that were previously considered as sterile; for example, liver, pancreas, brain and adipose tissue. Presently one of the etiological factors for liver disease is considered to be pro-inflammatory changes in a host’s organism. There are lot of supporting data about intestinal dysbiosis and increased intestinal permeability and its effect on development of liver disease pointing to the gut–liver axis. The gut–liver axis affects pathogenesis of many liver diseases, such as chronic hepatitis B, chronic hepatitis C, alcoholic liver disease, non-alcoholic liver disease, non-alcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma. Gut microbiota has been implicated in the regulation of brain health, emphasizing the gut–brain axis. Also, experiments with mice showed that microorganisms have significant effects on the blood–brain barrier integrity. Microbiota can modulate a variety of mechanisms through the gut–liver axis and gut–brain axis. Normal intestinal flora impacts the health of a host in many positive ways, but there is now significant evidence that intestinal microbiota, especially altered, have the ability to impact the pathologies of many diseases through different inflammatory mechanisms. At this point, many of the pathophysiological reactions in case of microbial disbyosis are still unclear.
Methylamine Activates Glucose Uptake in Human Adipocytes Without Overpassing Action of Insulin or Stimulating its Secretion in Pancreatic Islets
Authors: Carpéné Christian , Mauriège Pascale , Boulet Nathalie , Biron Simon , Grolleau Jean-Louis , Garcia-Barrado Maria José , Iglesias-Osma Mari Carmen
Published: August 2019

Background: Methylamine, a natural soluble amine present in foods, is known to be a substrate of primary amine oxidase (PrAO) widely expressed in animal tissues. Methylamine has been reported to activate glucose transport in fat cells and to facilitate glucose disposal in rabbits but the interests and limits of such insulin-mimicking actions have not been further explored. This work aimed to perform a preclinical study of the inter-individual variations of these biological properties to study the putative link between PrAO activity and insulin resistance. Methods: Methylamine was tested on human adipocyte preparations and in rabbit pancreatic islets to determine its influence on glucose uptake and insulin release, respectively. PrAO activity and related responses were determined in adipose tissues obtained from two cohorts of non-obese and obese women. Results: Adipose tissue PrAO activity was negatively correlated with insulin resistance in high-risk obese women. PrAO-dependent activation of glucose uptake was negatively correlated with body mass index and reflected the decrease of insulin responsiveness of human fat cells with increasing obesity. Methylamine exhibited antilipolytic properties in adipocytes but was unable to directly activate insulin secretion in isolated pancreatic islets. Conclusions: PrAO activation by its substrates, e.g., methylamine, increases glucose utilization in human adipocytes in a manner that is linked to insulin responsiveness. Methylamine/PrAO interaction can therefore contribute to adipose tissue enlargement but should be considered as potentially useful for diabetes prevention since it could limit lipotoxicity and facilitate glucose handling, at the expense of favoring healthy fat accumulation.
Recent Advances in Electrochemiluminescence Sensors for Pathogenic Bacteria Detection
Authors: Shen Jinjin , Zhou Ting , Huang Ru
Published: August 2019

Pathogenic bacterial contamination greatly threats human health and safety. Rapidly biosensing pathogens in the early stage of infection would be helpful to choose the correct drug treatment, prevent transmission of pathogens, as well as decrease mortality and economic losses. Traditional techniques, such as polymerase chain reaction and enzyme-linked immunosorbent assay, are accurate and effective, but are greatly limited because they are complex and time-consuming. Electrochemiluminescence (ECL) biosensors combine the advantages of both electrochemical and photoluminescence analysis and are suitable for high sensitivity and simple pathogenic bacteria detection. In this review, we summarize recent advances in ECL sensors for pathogenic bacteria detection and highlight the development of paper-based ECL platforms in point of care diagnosis of pathogens.
Improvement of the Bias Stress Stability in 2D MoS2 and WS2 Transistors with a TiO2 Interfacial Layer
Authors: Park Woojin , Pak Yusin , Jang Hye Yeon , Nam Jae Hyeon , Kim Tae Hyeon , Oh Seyoung , Choi Sung Mook , Kim Yonghun , Cho Byungjin
Published: August 2019

The fermi-level pinning phenomenon, which occurs at the metal–semiconductor interface, not only obstructs the achievement of high-performance field effect transistors (FETs) but also results in poor long-term stability. This paper reports on the improvement in gate-bias stress stability in two-dimensional (2D) transition metal dichalcogenide (TMD) FETs with a titanium dioxide (TiO2) interfacial layer inserted between the 2D TMDs (MoS2 or WS2) and metal electrodes. Compared to the control MoS2, the device without the TiO2 layer, the TiO2 interfacial layer deposited on 2D TMDs could lead to more effective carrier modulation by simply changing the contact metal, thereby improving the performance of the Schottky-barrier-modulated FET device. The TiO2 layer could also suppress the Fermi-level pinning phenomenon usually fixed to the metal–semiconductor interface, resulting in an improvement in transistor performance. Especially, the introduction of the TiO2 layer contributed to achieving stable device performance. Threshold voltage variation of MoS2 and WS2 FETs with the TiO2 interfacial layer was ~2 V and ~3.6 V, respectively. The theoretical result of the density function theory validated that mid-gap energy states created within the bandgap of 2D MoS2 can cause a doping effect. The simple approach of introducing a thin interfacial oxide layer offers a promising way toward the implementation of high-performance 2D TMD-based logic circuits.
Lack of Association between Past Helicobacter pylori Infection and Diabetes: A Two-Cohort Study
Authors: Pyo Jeung Hui , Lee Hyuk , Choi Sung Chul , Cho Soo Jin , Choi Yoon-Ho , Min Yang Won , Min Byung-Hoon , Lee Jun Haeng , Yoo Heejin , Kim Kyunga , Kim Jae J.
Published: August 2019

Helicobacter pylori (H. pylori) may be involved in diabetes and other insulin-related processes. This study aimed to investigate the associations between H. pylori infection and the risks of type 2 diabetes, impaired glucose tolerance (IGT), diabetic nephropathy, and poor glycemic control. We retrospectively evaluated 16,091 subjects without diabetes at baseline who underwent repeated health examinations. Subjects were categorized according to whether they were seropositive and seronegative for H. pylori infection. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models. The serological results were validated using an independent cohort (n = 42,351) based on a histological diagnosis of H. pylori infection. During 108,614 person-years of follow-up, 1338 subjects (8.3%) developed newly diagnosed diabetes, although the cumulative incidence of diabetes was not significantly related to serological H. pylori status. The multivariate Cox proportional-hazards regression models revealed that H. pylori seropositivity was not significantly associated with diabetes (HR: 1.01, 95% CI: 0.88–1.16; p = 0.854), IGT (HR: 0.98, 95% CI: 0.93–1.04; p = 0.566), diabetic nephropathy (HR: 0.99, 95% CI: 0.82–1.21; p = 0.952), or poor glycemic control (HR: 1.05, 95% CI: 0.90–1.22; p = 0.535). Similarly, histopathological findings of H. pylori infection were not significantly associated with diabetes (p = 0.311), diabetic nephropathy (p = 0.888), or poor glycemic control (p = 0.989). The findings from these large Korean cohorts indicate that there does not appear to be a role for past H. pylori infection in the development of diabetes, IGT, diabetic nephropathy, or poor glycemic control.
Exercise-Induced Oxidative Stress, Nitric Oxide and Plasma Amino Acid Profile in Recreational Runners with Vegetarian and Non-Vegetarian Dietary Patterns
Authors: Nebl Josefine , Drabert Kathrin , Haufe Sven , Wasserfurth Paulina , Eigendorf Julian , Tegtbur Uwe , Hahn Andreas , Tsikas Dimitrios
Published: August 2019

This study investigated the exercise-induced changes in oxidative stress, nitric oxide (NO) metabolism and amino acid profile in plasma of omnivorous (OMN, n = 25), lacto-ovo-vegetarian (LOV, n = 25) and vegan (VEG, n = 23) recreational runners. Oxidative stress was measured as malondialdehyde (MDA), NO as nitrite and nitrate, and various amino acids, including homoarginine and guanidinoacetate, the precursor of creatine. All analytes were measured by validated stable-isotope dilution gas chromatographic-mass spectrometric methods. Pre-exercise, VEG had the highest MDA and nitrate concentrations, whereas nitrite concentration was highest in LOV. Amino acid profiles differed between the groups, with guanidinoacetate being highest in OMN. Upon acute exercise, MDA increased in the LOV and VEG group, whereas nitrate, nitrite and creatinine did not change. Amino acid profiles changed post-exercise in all groups, with the greatest changes being observed for alanine (+28% in OMN, +21% in LOV and +28% in VEG). Pre-exercise, OMN, LOV and VEG recreational runners differ with respect to oxidative stress, NO metabolism and amino acid profiles, in part due to their different dietary pattern. Exercise elicited different changes in oxidative stress with no changes in NO metabolism and closely comparable elevations in alanine. Guanidinoacetate seems to be differently utilized in OMN, LOV and VEG, pre- and post-exercise.
Intestinal Permeability and Drug Absorption: Predictive Experimental, Computational and In Vivo Approaches
Authors: Dahlgren David , Lennernäs Hans
Published: August 2019

The main objective of this review is to discuss recent advancements in the overall investigation and in vivo prediction of drug absorption. The intestinal permeability of an orally administered drug (given the value Peff) has been widely used to determine the rate and extent of the drug’s intestinal absorption (Fabs) in humans. Preclinical gastrointestinal (GI) absorption models are currently in demand for the pharmaceutical development of novel dosage forms and new drug products. However, there is a strong need to improve our understanding of the interplay between pharmaceutical, biopharmaceutical, biochemical, and physiological factors when predicting Fabs and bioavailability. Currently, our knowledge of GI secretion, GI motility, and regional intestinal permeability, in both healthy subjects and patients with GI diseases, is limited by the relative inaccessibility of some intestinal segments of the human GI tract. In particular, our understanding of the complex and highly dynamic physiology of the region from the mid-jejunum to the sigmoid colon could be significantly improved. One approach to the assessment of intestinal permeability is to use animal models that allow these intestinal regions to be investigated in detail and then to compare the results with those from simple human permeability models such as cell cultures. Investigation of intestinal drug permeation processes is a crucial biopharmaceutical step in the development of oral pharmaceutical products. The determination of the intestinal Peff for a specific drug is dependent on the technique, model, and conditions applied, and is influenced by multiple interactions between the drug molecule and the biological membranes.