bluuebunny/crossref_metadata_2025 huggingface dataset:
Occupational exposure to solvents and lung function decline: A population based study
Authors: Alif Sheikh M , Dharmage Shyamali , Benke Geza , Dennekamp Martine , Burgess John , Perret Jennifer L , Lodge Caroline , Morrison Stephen , Johns David Peter , Giles Graham , Gurrin Lyle , Thomas Paul S , Hopper John Llewelyn , Wood-Baker Richard , Thompson Bruce , Feather Iain , Vermeulen Roel , Kromhout Hans , Jarvis Debbie , Garcia Aymerich Judith , Walters E Haydn , Abramson Michael J , Matheson Melanie Claire
Published: April 2019

Rationale

While cross-sectional studies have shown associations between certain occupational exposures and lower levels of lung function, there was little evidence from population-based studies with repeated lung function measurements.

Objectives

We aimed to investigate the associations between occupational exposures and longitudinal lung function decline in the population-based Tasmanian Longitudinal Health Study.

Methods

Lung function decline between ages 45 years and 50 years was assessed using data from 767 participants. Using lifetime work history calendars completed at age 45 years, exposures were assigned according to the ALOHA plus Job Exposure Matrix. Occupational exposures were defined as ever exposed and cumulative exposure -unit- years. We investigated effect modification by sex, smoking and asthma status.

Results

Compared with those without exposure, ever exposures to aromatic solvents and metals were associated with a greater decline in FEV1(aromatic solvents 15.5 mL/year (95% CI −24.8 to 6.3); metals 11.3 mL/year (95% CI −21.9 to – 0.7)) and FVC (aromatic solvents 14.1 mL/year 95% CI −28.8 to – 0.7; metals 17.5 mL/year (95% CI –34.3 to – 0.8)). Cumulative exposure (unit years) to aromatic solvents was also associated with greater decline in FEV1and FVC. Women had lower cumulative exposure years to aromatic solvents than men (mean (SD) 9.6 (15.5) vs 16.6 (14.6)), but greater lung function decline than men. We also found association between ever exposures to gases/fumes or mineral dust and greater decline in lung function.

Conclusions

Exposures to aromatic solvents and metals were associated with greater lung function decline. The effect of aromatic solvents was strongest in women. Preventive strategies should be implemented to reduce these exposures in the workplace.
Performance, intestinal morphometry, and incubation parameters of broiler chickens submitted to in ovo feeding with different techniques and amino acids
Authors: Groff-Urayama Priscila , Padilha Joselaine , Einsfeld Suelen , Pertile Simone , Gorges Mateus , de Andrade Mariana , di Domenico Adriana , Maeda Emilyn Midori , Takahashi Sabrina
Published: April 2019

The objective of this research was to evaluate techniques, incubation period, and effects of amino acids in ovo feeding. First, 240 hatching eggs were selected and distributed in a 2 × 3 factorial arrangement (two techniques and 3 d). The parameters of incubation, relative weight of gastrointestinal organs, and classification of embryonic mortality were evaluated. In the second stage, 720 hatching eggs were incubated with five treatments: control, methionine (20 and 30 mg), and lysine (20 and 30 mg). These animals were housed during 14 d. The animals were divided with five treatments, nine replicates, and groupings based on sex. Incubation parameters, performance, intestinal morphometry, and relative weight of digestive tract organs were evaluated. The results indicate that the technique using a 45° needle axis passing through the air chamber hinders hatchability. In the organ weighing, there was no difference between the evaluated factors. For intestinal morphometry, there was only a significant difference between the dose factor for the crypt villi and crypt diameter. To conclude, the technique using a 90° angle without passing through the air chamber is safer for the embryos. The inoculation of methionine (20 and 30 mg) obtained data similar to the control group.
Genetic correlations among selected traits in Canadian Holsteins
Authors: Martin P. , Baes C. , Houlahan K. , Richardson C.M. , Jamrozik J. , Miglior F.
Published: April 2019

In the Canadian dairy industry, there are currently over 80 traits routinely evaluated, and more are considered for potential selection. Particularly, in the last few years, recording has commenced for several new phenotypes required to introduce novel traits with high economic importance into the selection program. However, without a systematic estimation of the genetic correlations that exist among traits, the potential results of indirect selection are unknown. Therefore, 29 traits representative of the trait diversity for first lactation Canadian animals were selected. Their two-by-two genetic correlations were estimated from a dataset of 62 498 first lactation Holstein cows, using a Markov Chain Monte Carlo Gibbs sampling approach. The general tendencies among the groups of traits confirm that production traits are negatively correlated with fertility traits and that functional traits are positively correlated with one another. The association of udder depth with fertility and disease resistance has also been highlighted. This contribution offers a comprehensive overview of current estimates across traits and includes correlations with novel traits that constitute an original addition to the literature. These new estimates can be used for newly developed genomic evaluation models and possibly lead to more accurate estimations of the dairy cows’ overall genetic merit.
Retail lamb fat composition in western Canada
Authors: Dugan M.E.R. , Salazar V. , Rolland D.C. , Vahmani P. , Aalhus J.L. , López-Campos Ó. , Prieto N. , Juárez M.
Published: April 2019

The fatty acid composition of retail lamb backfat commonly available in Western Canada was analyzed, including 16 lambs collected from a slaughter plant in central Alberta, and backfat collected from racks and chops imported from Australia (n = 8) and New Zealand (n = 8). Lamb fat from New Zealand was the richest source of vaccenic and rumenic acids. Both New Zealand and Australian lamb were the richest source of n-3 fatty acids. North American lamb was richer in t10-18:1, but a subset had fatty acid compositions similar to New Zealand lamb.
Soil fauna affects the optical properties in alkaline solutions extracted (humic acid-like) from forest litters during different phenological periods
Authors: Tan Yu , Yang Wanqin , Ni Xiangyin , Tan Bo , Yue Kai , Cao Rui , Liao Shu , Wu Fuzhong
Published: April 2019

The formation of soil organic matter via humification of plant litter is important for long-term carbon sequestration in forests; however, whether soil fauna affects litter humification is unclear. In this study, we quantified the effects of soil fauna on the optical properties (i.e., ΔlogK and E4/E6) of the alkaline-extracted humic acid-like solutions of four foliar litters by removing soil fauna via litterbags with different mesh sizes in two subtropical evergreen broad-leaved forests. Litterbags were collected at the leaf falling, budding, expanding, maturation, and senescence stages from November 2013 to October 2015 to assess whether the effects of soil fauna on litter humification vary in different plant phenology periods. The results showed that soil fauna significantly reduced the ΔlogK and E4/E6 values in the leaf expanding stage of oak litter and in the leaf falling stage of camphor and fir litters. The richness index of soil fauna explained 21%, 55%, 19%, and 45% of the variations in the E4/E6 values for oak, fir, camphor, and pine litters, respectively. The effects of litter water content on these optical properties were greater than that of temperature. These results indicated that soil fauna plays a key role in litter humification in the leaf expanding and falling stages and are potentially involved in soil carbon sequestration in these subtropical forests.
Effects of the combined application of biomaterial amendments and polyacrylamide on soil water and maize growth under deficit irrigation
Authors: Hu Yajin , Guo Nini , Hill Robert L. , Wu Shufang , Dong Qin’ge , Ma Penghui
Published: April 2019

Combined applications of mixed biomaterial amendments and polyacrylamide (MBAP) to maize in semiarid areas have the potential to improve soil physical properties such that improved crop performance may be obtained under deficient irrigation management. In this study, three MBAP applications were C0 (conventional N fertilization application) and C2 and C4 (MBAP applied at rates of 2 and 4 t ha−1, respectively); three irrigation levels were W3 (nearly full irrigation, 85%–100% of field capacity), W2 (light deficit irrigation, 65%–75% of field capacity), and W1 (medium deficit irrigation, 55%–65% of field capacity). Under the same irrigation level, the MBAP significantly decreased soil bulk densities and increased soil hydraulic conductivities and soil water contents. The effects of irrigation levels on soil bulk densities and soil saturated hydraulic conductivities were not significant. Consequently, MBAP improved soil conditions for maize growth and increased grain and biomass yields, especially at the two deficit irrigation levels. Compared with that of C0, grain yields for C2 and C4 were increased by 52.8% and 39.3% under W2, and by 23.5% and 13.7% under W1, respectively. The MBAP and irrigation had significant interaction effects on evapotranspiration during sowing to jointing and on plant heights at 32 d after sowing. The incorporation of MBAP (2 t ha−1) and chemical fertilizer (111.8 kg N ha−1) resulted in the greatest yields under light deficit irrigation and seemed the best approach to improve soil physical properties and sustain maize productivity using limited water resources in dryland regions.
Latitudinal gradient in cortisol concentrations in Canada lynx (Lynx canadensis) is not explained by diet
Authors: Burstahler C.M. , Terwissen C.V. , Roth J.D.
Published: April 2019

Food limitation is an important stressor for most wildlife, and many specialist consumers will expand their dietary niche to contend with preferred prey limitation. How these dietary responses feed back into stress-axis regulation, however, is unknown. If alternative prey does not sufficiently fill the energetic requirements normally satisfied by preferred resources, then long-term glucocorticoid concentrations could be elevated in individuals consuming alternative prey. We measured cortisol concentrations and stable isotope ratios (δ13C and δ15N) in hair of Canada lynx (Lynx canadensis Kerr, 1792) across their distribution to determine the influence of diet on glucocorticoids while controlling for harvest location. We calculated the Euclidean distance between lynx and regional snowshoe hare (Lepus americanus Erxleben, 1777) stable isotope ratios as an index of diet specialization. We found no relationship between this index and cortisol, suggesting that prey types are interchangeable for lynx in terms of long-term stress axis activation. However, lynx cortisol increased significantly towards the northwestern region of lynx distribution, contrasting with our prediction, and highlighting important considerations for future research. This combination of glucocorticoid and diet analyses suggests that dietary plasticity does not necessarily alter an individual’s experience of potential stressors, despite important implications to population and community dynamics.
Cardamonin Induces Cell Cycle Arrest, Apoptosis and Alters Apoptosis Associated Gene Expression in WEHI-3 Mouse Leukemia Cells
Authors: Liao Nien-Chieh , Shih Yung-Luen , Chou Jiann-Shang , Chen Kuo-Wei , Chen Yung-Liang , Lee Mei-Hui , Peng Shu-Fen , Leu Sy-Jye , Chung Jing-Gung
Published: April 2019

Cardamonin, the chalcone class, is one of the natural components from the spicy herbaceous plant (Alpinia conchigera Griff) and has anticancer activities in many human cancer cell lines. There is, however, no information to show that cardamonin induces cell apoptosis and alters apoptosis associated gene expressions in mouse leukemia cells. Thus, we investigated the effects of cardamonin on the apoptotic cell death and associated gene expression in mouse leukemia WEHI-3 cells in vitro. Results indicated that cardamonin decreased total viable cell number via induced cell morphological changes and apoptotic cell death in WEHI-3 cells that were assay by contrast-phase microscopy and flow cytometry examinations, respectively. The flow cytometry assay indicated that cardamonin increased reactive oxygen species (ROS) and Ca[Formula: see text] production, decreased the levels of mitochondrial membrane potential ([Formula: see text] and increased caspase-3, -8 and -9 activities in WEHI-3 cells. Western blotting was performed to analyze expression of relevant pro- and anti-apoptotic proteins and results showed that cardamonin decreased anti-apoptotic protein of Bcl-2 but increased pro-apoptotic protein of Bax in WEHI-3 cells. Furthermore, cardamonin increased cytochrome c, AIF and Endo G release, increased GRP78, caspase-12 that were associated with ER stress and increased Fas, Fas-Ligand and FADD expression. Furthermore, cardamonin increased the gene expressions of DAP (death-associated protein), TMBIM4 transmembrane (BAX inhibitor motif containing 4), ATG5 (autophagy related 5) but decreased the gene expression of DDIT3 (DNA-damage inducible transcript 3), DDIT4 (DNA-damage-inducible transcript 4), BAG6 (BCL2-associated athanogene 6), BCL2L13 [BCL2-like 13 (apoptosis facilitator)] and BRAT1 (BRCA1-associated ATM activator 1) that are associated with apoptosis pathways. Based on those findings, we may suggest cardamonin induced apoptotic cell death through Fas and Fas-Ligand-, caspase- and mitochondria-dependently pathways and also affects the apoptotic gene expression in WEHI-3 cells in vitro.
Method for Detecting Chinese Texts in Natural Scenes Based on Improved Faster R-CNN
Authors: Liu Shuhua , Ban Hua , Song Yu , Zhang Mengyu , Yang Fengqin
Published: April 2019

In this study, a natural scene text detection method based on the improved faster region-based convolutional neural network (R-CNN) is proposed. This method extracts image features with the Inception-ResNet architecture, adopts a region proposal network to generate region proposals for the extracted features, merges the fine-tuned features with the region proposals, and finally, uses Fast R-CNN to classify and locate text. The proposed method solves the problems of varying text sizes and the text being obscured in the image. Compared with the original Faster R-CNN, the multilevel Inception-ResNet network model presented in this study can extract deeper text features. The extracted feature map is further sparsely represented by Reduction B, Inception ResNet C and Avg Pool, and then is fused with text regions obtained by the text feature mapping lower layer network to acquire the exact text regions. The text detection method presented in this study is tested on the 2017 dataset of ICDAR2017 Competition on Reading Chinese Text in the Wild (RCTW-17), which contains a large number of distorted, blurry, different scale and size texts. An accuracy of 76.4% is achieved in this platform, thereby proving the efficiency of the proposed method.
Toward a Unified Performance Metric for Benchmarking Steganography Systems
Authors: Rabie Tamer , Baziyad Mohammed , Bonny Talal , Fareh Raouf
Published: April 2019

Recent advances in network speeds for exchanging multimedia data over insecure networks has resulted in an increased interest in steganography techniques. These techniques are usually evaluated based on their performance in three attributes; namely, capacity, imperceptibility, and robustness. Each of these attributes has its own measurement metric. Hence, comparing two different steganography schemes based on these individual metric tools becomes inconsistent. In this paper, a novel measurement metric tool is introduced for benchmarking steganography schemes. This new tool, named the “Combined Capacity-Quality-Robustness Effectiveness” (CCQRE) metric, combines the three opposing attributes of a steganography system into one conglomerate performance measure. Comparative results demonstrate the effectiveness of the proposed CCQRE metric for benchmarking various steganography schemes based on the researcher’s interest in capacity, imperceptibility, or robustness.
An Efficient and High-Speed Implementation of QRD-MGS Algorithm for STAP Application Based on Floating Point FPGAs
Authors: Hasanikhah Narjes , Amin-Nejad Siavash , Darvish Ghafar , Moniri M. R.
Published: April 2019

Space-Time Adaptive Processing (STAP) can harness the efficacy of interference and clutter significantly. Calculations of the STAP weights involve solving linear equations which require very intensive computations. In this paper, the QR decomposition (QRD) using the modified gram-schmidt (MGS) algorithm is parameterized with vector size to create a trade-off between the hardware resources utilization and computation time. To achieve an efficient floating point structure, the proposed architecture of QRD-MGS algorithm is simulated and implemented in two modes: single-vector and multi-vector. Results show that the multi-vector method can lead to a high-performance design with higher operating frequency, lower power consumption, and less resource utilization than the single-vector method. For example, Modelism simulations show that the decomposition of a [Formula: see text] matrix with vector size of 17 takes 7.86[Formula: see text][Formula: see text]s with the maximum clock frequency of 282[Formula: see text]MHz, for implementation on the Arria10 FPGA. In real STAP applications, the matrix sizes are too large to be fit on FPGAs and the update rate of the weights are high. Therefore, this method can fit any matrix in the contemporary FPGAs with an acceptable update rate.
An Ultra-Low-Power, 16 Bits CT Delta-Sigma Modulator Using 4-Bit Asynchronous SAR Quantizer for Medical Applications
Authors: Javahernia Sahel , Aghdam Esmaeil Najafi , Torkzadeh Pooya
Published: April 2019

In this paper, a low-power second-order feed-forward capacitor-structure continuous-time [Formula: see text] modulator with a 4-bit asynchronous successive approximation register (SAR) quantizer is presented. Through the utilization capacitor structure in the proposed modulator, first, the summation node of the integrators’ outputs and the feed-forward signals is implemented within the second integrator to reduce power consumption by eliminating an active summing amplifier. Second, the proposed architecture can compensate for the quantizer delay without using any excess inner digital to analog converter (DAC). In this design, the modulator applies two different low-power operational amplifiers. These advantages cause the modulator to consume very low power and achieve a favorable figure of merit (FOM) value. In fact, in this paper, the combination of the previously reported methods and designs and doing required reforms has led to a new design with better performance, especially in power reduction. The designed modulator which is simulated using 0.18[Formula: see text][Formula: see text]m CMOS technology achieves 95.98[Formula: see text]dB peak signal-to-noise and distortion (SNDR) for 10[Formula: see text]KHz signal bandwidth and dissipates 44[Formula: see text][Formula: see text]w while its FOM is obtained about 43 fJ/conv.-step.
Migrative Property for Semi-t-Operators
Authors: Zong Wenwen , Su Yong , Liu Hua-Wen
Published: April 2019

Recently, the α-migrativity has been discussed in families of certain operations (e.g., triangular norms, conorms, uninorms, and nullnorms). In this paper, the migrative property for semi-t-operators is studied. All solutions of the migrativity equation for all possible combinations of semi-t-operators are analyzed and characterized.
Fuzzy-Logic-Based Asset Allocation
Authors: North Reiner
Published: April 2019

This paper provides an introduction to how, on the basis of concepts from fuzzy logic, a model of asset allocation can be constructed which can represent and aggregate all the relevant quantitative and qualitative features of an investment plan realistically and in this way attains comparatively good recommendations like an expert. All calculation steps are carried out in a transparent and reproducible manner. In order to clarify the approach and the advantages of the procedure, a pilot model is developed. This supports the advisor with the asset allocation, by first analysing the features of the investment goal and the market expectations and then evaluating the merits of several investment strategies as well as displaying the steps towards their evaluation in a comprehensible manner. Based on case studies, the results of the pilot model are compared with known good recommendations from an investigation of Stiftung Warentest on the quality of advice in banks.
Gorenstein FC-projective modules
Authors: Wang Yu , Zhou Dexu
Published: April 2019

In this paper, we investigate Gorenstein FC-projective modules and Gorenstein FC-projective dimensions, and characterize rings over which every module is Gorenstein FC-projective and rings over which every submodule of a projective is Gorenstein FC-projective, respectively. Under an almost excellent extension of rings, we obtain several invariant properties of Gorenstein FC-projective modules and Gorenstein FC-projective dimensions.
AVIAN INNATE IMMUNITY WITH AN EMPHASIS ON CHICKEN MELANOMA DIFFERENTIATION-ASSOCIATED GENE 5 (MDA5)
Authors: Lee Chih-Chun , Tung Chun-Yu , Wu Ching Ching , Lin Tsang Long
Published: April 2019

Avian species have immune system to fight invading pathogens. The immune system comprises innate and adaptive immunity. Innate immunity relies on pattern recognition receptors to sense particular molecules present in pathogens, i.e. pathogen-associated molecular patterns (PAMPs), or danger signals in the environment, i.e. danger-associated molecular patterns (DAMPs). Cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs) are the sensors recognizing cytoplasmic PAMP and/or DAMP. Among common avian species, chickens do not have RIG-I whereas ducks and finches do. Therefore, the other RLR member, melanoma differentiation-associated gene 5 (MDA5), is believed to play an important role to recognize intracellular pathogens in chickens. Chicken MDA5 has been identified and its function determined. Chicken MDA5 maintains the same domain architecture compared with MDA5 analogs in other animal species. The expression of chicken MDA5 was upregulated when a synthetic double-stranded RNA (dsRNA), polyriboinosinic:polyribocytidylic acids (poly(I:C)), was transfected into chicken cells, whereas that did not change when cells were incubated with poly(I:C). The enhanced expression of chicken MDA5 in chicken cells upregulated the expression of chicken interferon-[Formula: see text] (IFN-[Formula: see text]). The infection of dsRNA infectious bursal disease virus (IBDV) in non-immune cells triggered the activation of chicken MDA5 signaling pathway, leading to the production of IFN-[Formula: see text] and subsequent response of IFN-stimulated genes. Furthermore, in immune cells like macrophages, chicken MDA5 participated in sensing the infection of IBDV by activating downstream antiviral genes and molecules and modulating adaptive immunity.

On the contrary, one of cytoplasmic NLR member, NLR family pyrin domain containing 3 (NLRP3), was cloned and functionally characterized in chicken cells. Chicken NLRP3 conserved the same domain architecture compared with NLRP3 analogs in other animal species. Chicken NLRP3 was highly expressed in kidney, bursa of Fabricius and spleen. The production of mature chicken interleukin 1 [Formula: see text] (IL-1[Formula: see text] in chicken macrophages was stimulated by lipopolysaccharide (LPS) treatment followed by short ATP exposure.

In summary, chicken MDA5 was a cytoplasmic dsRNA sensor that mediated the production of type I IFN upon ligand engagement, whereas NLRP3 sensed danger signals, such as ATP, in the cytoplasm and cleaved pro-IL-1[Formula: see text] to produce mature IL-1[Formula: see text]. Chicken MDA5 was not only involved in the activation of innate immune responses in non-immune and immune cells, but it also participated in modulating adaptive immunity in immune cells. Chicken NLRP3 participated in the production of mature chicken IL-1[Formula: see text] upon ligand engagement.
Annihilating-ideal graphs of commutative rings
Authors: Aijaz M. , Pirzada S.
Published: April 2019

Let [Formula: see text] be a commutative ring with unity [Formula: see text]. The annihilating-ideal graph of [Formula: see text], denoted by [Formula: see text], is defined to be the graph with vertex set [Formula: see text] — the set of non-zero annihilating ideals of [Formula: see text] and two distinct vertices [Formula: see text] and [Formula: see text] adjacent if and only if [Formula: see text]. Some connections between annihilating-ideal graphs and zero divisor graphs are given. We characterize the prime ideals (or equivalently maximal ideals) of [Formula: see text] in terms of their degrees as vertices of [Formula: see text]. We also obtain the metric dimension of annihilating-ideal graphs of commutative rings.
Detrital zircon record from major rivers of Luzon Island: implications for Cenozoic continental growth in SE Asia
Authors: Tsai Chia-Hsin , Shyu J. Bruce H. , Chung Sun-Lin , Ramos Noelynna T. , Lee Hao-Yang
Published: April 2019

The significance of continental crustal growth in the Phanerozoic has long been debated. As an active accretionary orogenic belt, SE Asia has been proposed to be one of the best archives for studying juvenile continental growth in the Cenozoic, despite the limited availability of data. Therefore, we conducted for the first time a comprehensive U–Pb and Hf isotopic analysis of detrital zircons separated from major rivers of Luzon Island, the largest landmass of the Philippine Archipelago. U–Pb ages of these zircons are predominantly <50 Ma, consistent with literature zircon U–Pb ages or whole-rock K–Ar ages. A sample from the central Sierra Madre, however, contains zircons with age clusters at 110–70 and 180–140 Ma, supporting the presence of Mesozoic basement rock units in that area. All dated zircons show positive and high εHf(T) values that plot close to the depleted mantle. Therefore, we argue that pre-Cenozoic continental materials played insignificant roles in the construction of Luzon Island, and that this part of the southeastern Eurasian margin consists predominantly of a juvenile terrane where substantial continental crustal growth occurred in the Cenozoic.

Supplementary material:
U–Pb ages and Hf isotopic results for detrital zircons from all samples are available at
https://doi.org/10.6084/m9.figshare.c.4481882
Load-indentation testing to assess porewater pressure effects on linear drag and disc cutting of a saturated permeable brittle rock
Authors: Abu Bakar M. Z. , Majeed Y.
Published: April 2019

In this study load-indentation tests with porewater pressure measurement were conducted to explore the unexpected differences owing to water saturation in the linear cutting of a permeable quartzose sandstone using drag and disc type cutters. This was done to evaluate the probable role of porewater pressure in rock fragmentation by drag and disc type cutters. The contrasting response to water saturation of these two types of cutters might be explained by the effects of their different fragmentation mechanisms, such as the relative size of the crushed zone that forms beneath the cutters. The relationship between cutting speed and rock permeability was expected to be a major factor influencing the effective pressure beneath a cutter in saturated rock. However, load-indentation tests with pore pressure measurement at the same speed showed that the pore pressure within the tested sandstone remained too low to affect the rock fracture process. Other possible mechanisms are discussed.
Advanced Simulation of Droplet Microfluidics
Authors: Grimmer Andreas , Hamidović Medina , Haselmayr Werner , Wille Robert
Published: April 2019

The complexity of droplet microfluidics grows with the implementation of parallel processes and multiple functionalities on a single device. This poses a severe challenge to the engineer designing the corresponding microfluidic networks. In today’s design processes, the engineer relies on calculations, assumptions, simplifications, as well as his/her experiences and intuitions. To validate the obtained specification of the microfluidic network, usually a prototype is fabricated and physical experiments are conducted thus far. In case the design does not implement the desired functionality, this prototyping iteration is repeated—obviously resulting in an expensive and time-consuming design process. To avoid unnecessary debugging loops involving fabrication and testing, simulation methods could help to initially validate the specification of the microfluidic network before any prototype is fabricated. However, state-of-the-art simulation tools come with severe limitations, which prevent their utilization for practically relevant applications. More precisely, they are often not dedicated to droplet microfluidics, cannot handle the required physical phenomena, are not publicly available, and can hardly be extended. In this work, we present an advanced simulation approach for droplet microfluidics that addresses these shortcomings and, eventually, allows simulating practically relevant applications. To this end, we propose a simulation framework at the one-dimensional analysis model, which directly works on the specification of the design, supports essential physical phenomena, is publicly available, and is easy to extend. Evaluations and case studies demonstrate the benefits of the proposed simulator: While current state-of-the-art tools were not applicable for practically relevant microfluidic networks, the proposed simulator allows reducing the design time and costs, e.g., of a drug screening device from one person month and USD 1200, respectively, to just a fraction of that.
SSS
Authors: Du Gaoming , Liu Guanyu , Li Zhenmin , Cao Yifan , Zhang Duoli , Ouyang Yiming , Gao Minglun , Lu Zhonghai
Published: April 2019

Network-on-Chip (NoC) has become the de facto communication standard for multi-core or many-core System-on-Chip (SoC) due to its scalability and flexibility. However, an important factor in NoC design is temperature, which affects the overall performance of SoC—decreasing circuit frequency, increasing energy consumption, and even shortening chip lifetime. In this article, we propose SSS, a self-aware SoC using a static-dynamic hybrid method that combines dynamic mapping and static mapping to reduce the hotspot temperature for NoC-based SoCs. First, we propose monitoring and thermal modeling for self-state sensoring. Then, in static mapping stage, we calculate the optimal mapping solutions under different temperature modes using the discrete firefly algorithm to help self-decision making. Finally, in dynamic mapping stage, we achieve dynamic mapping through configuring NoC and SoC sentient units for self-optimizing. Experimental results show that SSS has substantially reduced the peak temperature by up to 37.52%. The FPGA prototype proves the effectiveness and smartness of SSS in reducing hotspot temperature.
Cardioprotective roles of sestrin 1 and sestrin 2 against doxorubicin cardiotoxicity
Authors: Li Ruiting , Huang Yin , Semple Ian , Kim Myungjin , Zhang Zunjian , Lee Jun Hee
Published: April 2019

Doxorubicin is a chemotherapy medication widely used to treat a variety of cancers. Even though it offers one of the most effective anti-cancer treatments, its clinical use is limited because of its strong cardiotoxicity that can lead to fatal conditions. Here, we show that sestrin 1 and sestrin 2, members of the sestrin family of proteins that are stress-inducible regulators of metabolism, are critical for suppressing doxorubicin cardiotoxicity and coordinating the AMPK-mammalian target of rapamycin complex 1 (mTORC1) autophagy signaling network for cardioprotection. Expression of both sestrin 1 and sestrin 2 was highly increased in the mouse heart after doxorubicin injection. Genetic ablation of sestrin 1 and sestrin 2 rendered mice more vulnerable to doxorubicin and exacerbated doxorubicin-induced cardiac pathologies including cardiomyocyte apoptosis and cardiac dysfunction. These pathologies were associated with strong dysregulation of the cardiac signaling network, including suppression of the AMPK pathway and activation of the mTORC1 pathway. Consistent with AMPK downregulation and mTORC1 upregulation, autophagic activity of heart tissue was diminished, leading to prominent accumulation of autophagy substrate, p62/SQSTM1. Taken together, our results indicate that sestrin 1 and sestrin 2 are important cardioprotective proteins that coordinate metabolic signaling pathways and autophagy to minimize cardiac damage in response to doxorubicin insult. Augmenting this protective mechanism could provide a novel therapeutic rationale for prevention and treatment of doxorubicin cardiotoxicity.

NEW & NOTEWORTHY Doxorubicin is a highly efficient chemotherapeutic medicine; however, its use is limited because of its strong cardiotoxicity. Here, we show that sestrin 1 and sestrin 2 are critical protectors of cardiomyocytes from doxorubicin damage. By upregulating AMPK and autophagic activities and suppressing mammalian target of rapamycin complex 1 and oxidative stress, sestrins counteract detrimental effects of doxorubicin on cardiomyocytes. Correspondingly, loss of sestrin 1 and sestrin 2 produced remarkable dysregulation of these pathways, leading to prominent cardiac cell death and deterioration of heart function.
Association of intronic DNA methylation and hydroxymethylation alterations in the epigenetic etiology of dilated cardiomyopathy
Authors: Tabish Ali M. , Arif Mohammed , Song Taejeong , Elbeck Zaher , Becker Richard C. , Knöll Ralph , Sadayappan Sakthivel
Published: April 2019

In this study, we investigated the role of DNA methylation [5-methylcytosine (5mC)] and 5-hydroxymethylcytosine (5hmC), epigenetic modifications that regulate gene activity, in dilated cardiomyopathy (DCM). A MYBPC3 mutant mouse model of DCM was compared with wild type and used to profile genomic 5mC and 5hmC changes by Chip-seq, and gene expression levels were analyzed by RNA-seq. Both 5mC-altered genes (957) and 5hmC-altered genes (2,022) were identified in DCM hearts. Diverse gene ontology and KEGG pathways were enriched for DCM phenotypes, such as inflammation, tissue fibrosis, cell death, cardiac remodeling, cardiomyocyte growth, and differentiation, as well as sarcomere structure. Hierarchical clustering of mapped genes affected by 5mC and 5hmC clearly differentiated DCM from wild-type phenotype. Based on these data, we propose that genomewide 5mC and 5hmC contents may play a major role in DCM pathogenesis.

NEW & NOTEWORTHY Our data demonstrate that development of dilated cardiomyopathy in mice is associated with significant epigenetic changes, specifically in intronic regions, which, when combined with gene expression profiling data, highlight key signaling pathways involved in pathological cardiac remodeling and heart contractile dysfunction.
Loss of Notch1 Activity Inhibits Prostate Cancer Growth and Metastasis and Sensitizes Prostate Cancer Cells to Antiandrogen Therapies
Authors: Rice Meghan A. , Hsu En-Chi , Aslan Merve , Ghoochani Ali , Su Austin , Stoyanova Tanya
Published: April 2019

Prostate cancer remains among the leading causes of cancer-related deaths in men. Patients with aggressive disease typically undergo hormone deprivation therapy. Although treatment is initially very successful, these men commonly progress to lethal, castration-resistant prostate cancer (CRPC) in 2 to 3 years. Standard therapies for CRPC include second-generation antiandrogens, which prolong patient lifespan by only several months. It is imperative to advance our understanding of the mechanisms leading to resistance to identify new therapies for aggressive prostate cancer. This study identifies Notch1 as a therapeutic target in prostate cancer. Loss of NOTCH1 in aggressive prostate cancer cells decreases proliferation, invasion, and tumorsphere formation. Therapeutic inhibition of Notch1 activity with gamma secretase inhibitors RO4929097 or DAPT in prostate cancer cells further results in decreased proliferative abilities. Loss of NOTCH1 and treatment of immunocompromised mice bearing prostate cancer xenografts with RO4929097 display significantly impaired tumor growth. Loss of NOTCH1 additionally decreased metastatic potential of prostate cancer cells in invasion assays in vitro as well as in vivo experiments. Moreover, treatment with gamma secretase inhibitors or NOTCH1 gene deletion synergized with antiandrogen therapies, enzalutamide or abiraterone, to decrease the growth of prostate cancer cells. Combination of gamma secretase inhibitors with abiraterone significantly inhibited cell migration and invasion, while combination with enzalutamide reversed enzalutamide-induced migration and invasion. These collective findings suggest loss of NOTCH1 delays growth of CRPC and inhibits metastasis, and inhibition of Notch1 activation in conjunction with second-generation antiandrogen therapies could delay growth and progression of prostate cancer.
Drug Use before and after Initiating Treatment with Acetylcholinesterase Inhibitors
Authors: Efjestad Anne Sverdrup , Ihle-Hansen Hege , Hjellvik Vidar , Engedal Knut , Blix Hege Salvesen
Published: April 2019

Background/Aims: The aim was to study the prevalence of use of different drugs prescribed for behavioral and psychological symptoms of dementia in persistent users of acetylcholinesterase inhibitors (AChEIs) before and after AChEI initiation, and to compare with the use in the general population. Methods: Use of antidepressants, antipsychotics, and analgesics in the 4 years before and 2 years after AChEI initiation was studied based on data from the Norwegian Prescription Database 2004–2016. Results: The prevalence of use of antidepressants and antipsychotics the year before AChEI initiation was twice the prevalence in the age-adjusted general population and continued to rise in the first 2 years after initiation of AChEIs. The prevalence of weak analgesics and antipsychotics increased strongly in the last year before AChEI initiation. The increase in the use of antidepressants started at least 4 years before initiation of AChEIs. Opioid use was generally lower than in the general population and was not influenced by AChEI initiation. Conclusion: Increased use of antidepressants and antipsychotics was observed both before and after initiation of AChEIs and may indicate that behavioral symptoms occur in a preclinical or early phase of Alzheimer’s disease. The prescription pattern of analgesics with a low use of opioids may indicate an undertreatment of pain in people with dementia.
Balance and Sound Conditions in Adults with Bilateral Cochlear Implants
Authors: Tonini Ross , Cohen Helen S. , Mulavara Ajitkumar P. , Sangi-Haghpeykar Haleh
Published: April 2019

Purpose: To determine if (1) balance is impaired in patients with bilateral cochlear implants compared to healthy controls and (2) the presence of sound, non-speech, or speech affects standing balance. Materials and Methods: Four patients with bilateral cochlear implants were tested on three balance conditions on Romberg tests on medium-density compliant foam with eyes closed, with head stationary or moving in yaw or pitch, under 5 sound conditions: no sound, ambient background noise, pink noise, foreign language, English language. Results: Dependent measures were duration of standing and kinematics. Three of four subjects performed well with head still and no sound, background noise, or pink noise. All subjects performed poorly during the head movement conditions when hearing either foreign-language or English words. Subjects could not perform enough head movements during yaw and pitch conditions for accurate kinematic measurements. Conclusion: The no-sound condition did not influence standing balance skills. The addition of ambient or pink noise also did not affect their balance. However, when subjects were distracted by paying attention to words, regardless whether or not they understood the words, standing balance skills deteriorated. Thus, distracted attention in these patients leads to impaired balance, which may impair functional motor skills.
“We are the people” e “we are (afraid of) the people”
Authors: Santos Maike Wile dos
Published: April 2019

O objetivo deste ensaio é (i) esclarecer a concepção de indivíduo e a teoria da justiça por trás de O Contrato Social (de Jean-Jacques Rousseau), e por trás de O Federalista (de Alexander Hamilton, James Madison, e John Jay); e (ii) apontar como essas distinções afetam as diferentes concepções acerca da combinação entre constitucionalismo e democracia para os autores. Especificamente, aponto como ambos se preocupam com o facciosismo e com a tirania da maioria, mas encaminham essas preocupações de maneiras bastante diferentes, em especial no tocante à questão da representação e do papel da vontade geral nos arranjos institucionais do Estado.
Os Princípios de Yogyakarta e a proteção de direitos fundamentais das minorias de orientação sexual e de identidade de gênero
Authors: Alamino Felipe Nicolau Pimentel , Del Vecchio Victor Antonio
Published: April 2019

O presente artigo pretende analisar os Princípios de Yogyakarta, bem como os de Yogyakarta+10, levando em conta sua natureza jurídica, além de conceituar minorias e analisar as infrações aos direitos humanos relativas a este grupo que, por suas características, têm, por vezes, suas condutas criminalizadas.
As competições de julgamento simulado como instrumento de ensino jurídico
Authors: Bianchini Carolina Bonini , Haertel Letícia Machado
Published: April 2019

O presente trabalho visa a apresentar o papel das competições de julgamento simulado, i.e. Moot Court Competitions, na educação em Direito Internacional dos Direitos Humanos (“DIDH”). Para isso, apresentar-se-á a experiência da Atividade de Cultura e Extensão da Faculdade de Direito da Universidade de São Paulo (FDUSP) “Atuação em Sistemas Regionais e Globais de Direitos Humanos”, a qual, além de promover o ensino do DIDH, envia anualmente competidores para três competições internacionais: a Competição de Julgamento Simulado do Sistema Interamericano de Direitos Humanos, a Price Media Law Moot Court Competition e a Nelson Mandela World Human Rights Moot Court Competition.

A fim de que se pudesse mensurar o impacto de tais competições no aprendizado e no desenvolvimento de habilidades dos alunos de graduação da FDUSP, foi aplicado um questionário a todos os estudantes que participaram de ao menos uma das competições oferecidas pelo grupo entre 2009 e 2017. No questionário, foi solicitado aos alunos que se autoavaliassem sobre diversas habilidades, antes e depois da participação nas competições. Dessa forma, o presente artigo apresenta os resultados da pesquisa empírica, concluindo pela efetividade das competições de julgamento simulado como instrumento de ensino.
New plant distribution records to Indian states and addition to the flora of Myanmar
Authors: Pradheep Kanakasabhapathi , Harish Ganjalagatta Dasaiah , Rathi Ranbir Singh , Kattukkunnel Joseph John , Sultan Sheikh Mohmmad , Naveen Khoisnam , Jaisankar Iyyappan , Pandey Anjula , Ahlawat Sudhir Pal , Gupta Rita
Published: April 2019

Plant genetic resource collection expedition across various parts of India and herbarium study of Amaranthus and Luffa genera at Botanical Survey of India (BSI), Kolkata and Coimbatore revealed the distribution of 18 plant taxa new to various Indian states/union territory, viz., Arunachal Pradesh (7), Andaman & Nicobar Islands (5), Jammu & Kashmir (3), Andhra Pradesh (2), Manipur (1), and Tamil Nadu (1).  Out of these, 14 taxa have importance as wild relatives of 12 crop species.  In addition, herbarium studies at the BSI, Kolkata revealed the natural distribution of a cucurbitaceous species – Siraitia siamensis in Myanmar, which remained unnoticed and unreported so far.  Locality of herbarium/ germplasm collection, habitat and other field observations have been highlighted here.
Nesting trees of the Red Giant Gliding Squirrel Petaurista petaurista (Mammalia: Rodentia: Sciuridae) in a tropical forest of Namdapha National Park, India
Authors: Krishna Murali Chatakonda , Kumar Awadhesh , Tripathi Om Prakash
Published: April 2019

The present study investigated the nesting habits of the Red Giant Gliding Squirrel in the tropical forest of Namdapha National Park, India within the time period of 2012–2013.  Gliding squirrel nest trees were located by searching for them with using spotlighting during evenings and early mornings.  For each den site we recorded data on nesting tree species, total height of tree, height of the nest on tree, tree diameter at breast height (DBH), and canopy connectivity of the nesting tree.  We observed P. petaurista using cavity nests (n=27) in eight tree species.  The majority of nest trees observed were in Altingia excelsa (40.7%) and Terminalia myriocarpa (22.2%).  Trees with less canopy connectivity were preferred for nesting where 59.3% of nest trees had <25% canopy connectivity.  Petaurista petaurista nested in trees with an average of 31.1±0.86m (Mean ± SE) height and the nests were located at a mean height of 17.8±0.89m (SE) (min & max: 9.3m & 35.2m).  Mean DBH of nesting trees was 70.6±0.98cm (SE) (min & max: 38.2cm & 168.8cm).  This data helps in filling the gaps on the denning ecology of the species and may be useful for the management and conservation purpose of forest trees.
The Nepal Pipewort Eriocaulon nepalense var. luzulifolium (Commelinids: Poales: Eriocaulaceae): a new distribution record for southern India
Authors: Soumya Murugan , Nair Maya Chandrasekaran
Published: April 2019

Eriocaulon nepalense var. luzulifolium (Mart.) Praj. & J. Parn is described as a new record for South India from Nelliyampathy hills of Kollengode range forests, Nemmara forest Division, Palakkad district, Kerala. A detailed taxonomic description, nomenclatural status and photographs of the plant parts have been provided.
Resource selection by Javan Slow Loris Nycticebus javanicus E. Geoffroy, 1812 (Mammalia: Primates: Lorisidae) in a lowland fragmented forest in Central Java, Indonesia
Authors: Sodik Mahfut , Pudyatmoko Satyawan , Yuwono Pujo Semedi Hargo , Imron Muhammad Ali
Published: April 2019

Habitat loss and forest fragmentation have negative impacts on Javan Slow Loris Nycticebus javanicus, a Critically Endangered nocturnal primate endemic to Java.  Reports confirmed that less than 9% of forest area remains on Java Island.  One of the remaining natural habitats of the Javan Slow Loris is the fragment of Kemuning Forest in Temanggung Regency, Central Java.  The purpose of this study was to determine resource selection and habitat variables that determine the presence of Javan Slow Loris.  Habitat variables measured were basal area, tree connectivity, crown coverage on tree stage, slope, elevation, and distance to river.  Data analysis performed was logistic regression, likelihood ratio test, and Akaike’s Information Criterion with a backward elimination procedure.  We also used direct observation and interviews with locals to collect data on environment and anthropogenic features of this forest.  The results showed that the Javan Slow Loris uses resources selectively on a microhabitat scale.  The habitat factors that influence the probability of resource selection by the species are canopy cover and slope.  Habitat characteristics preferred by the Javan Slow Loris in Kemuning Forest are secondary lowland tropical rainforest with dense canopy cover located on a steep slope with low level of habitat disturbances.  Although this study uses a small sample size, the expectation is that the results can be used as preliminary information for the habitat and population management of Javan Slow Loris in Kemuning Forest to guide conservation efforts and design management strategies.