bluuebunny/crossref_metadata_2025 huggingface dataset:
Connected creativity – a human centered community innovation platform in the context of product generation engineering
Authors: Albers Albert , Maul Ludwig , Heismann Robert , Bursac Nikola
Published: February 2018

In this paper, a concept for a community innovation platform is introduced focusing on human behavior of motivation and barriers in the context of product generation development. Building on the state of the art, a three year case study in cooperation with Dr. Ing. h.c. F. Porsche AG is at the core. In the first step of the study, a questionnaire and interviews are used to point out that a new attractive channel for ideas is needed. The three perspectives of users, experts and stakeholders are investigated in order to discover needs and preferences. Based on these findings, in a second step, a software prototype was designed and introduced in a pilot project with more than 200 users. Using a questionnaire and expert workshops, in the final step, this project is evaluated as appealing to the community, and the generated content is demonstrated to be valuable to specific activities of product generation development.
Reconstruction of the mass balance of Muztag Ata No. 15 glacier, eastern Pamir, and its climatic drivers
Authors: ZHU MEILIN , YAO TANDONG , YANG WEI , XU BAIQING , WU GUANJIAN , WANG XIAOJUN , XIE YING
Published: February 2018

The mass-balance of Muztag Ata No. 15 (MZ15) glacier in the eastern Pamir is reconstructed between 1980 and 2012 using an energy-based mass-balance model. The results show that this glacier has been characterized by obvious interannual mass-balance changes during 1980–2012 with a slightly positive mass balance during 1998–2012. Precipitation in the ablation season is a primary driver of these mass-balance fluctuations. Distinct changes in the mass-balance of MZ15 glacier between 1980–1997 and 1998–2012 are thought to be associated with changes in the regionally averaged meridional wind speed and corresponding precipitation in the ablation season. The negative and positive mass-balance phases during 1980–1997 and 1998–2012, respectively, were associated with northerly and southerly wind anomalies in the eastern Pamir and their corresponding decreasing and increasing precipitation. These changes in circulation appear to be linked to the mid-latitude climate. Finally, contrary to the variation of most glaciers on the Tibetan Plateau, glaciers in the Karakoram-western Kunlun-eastern Pamir appear to have retreated more slowly over the past 10 years than during the 1970s-2000. This contrasting trend may be caused by different changes in snowfall and different topography factors in different regions under warming and increased precipitation.
Discretion in property law: a study of judicial correction of registered title
Authors: Cooper SAA
Published: February 2018

This paper examines discretionary decision making in a property law context: the statutory power to correct a mistaken entry on the land register. This discretionary power has importance as an occasion when the allocation of property occurs without fixed rules but is put into the control of the court without guidance on content or goals. The case-law is studied using legal empirical analysis. The judicial approach is described and findings are analysed. The paper relates the conclusions to doctrinal and policy debates in land registration and discusses how the judicial input advances understanding of the registration system as an integrated whole.
Influence of postoperative pain and use of NSAID on heart rate variability of dairy cows
Authors: Frondelius Lilli , Hietaoja Juha , Pastell Matti , Hänninen Laura , Anttila Paula , Mononen Jaakko
Published: February 2018

This Research Communication describes the effect of post-operative pain and non-steroidal anti-inflammatory drug (NSAID) treatment on heart rate variability (HRV) of dairy cows. Postoperative pain in farm animals is often left untreated, and HRV could be a promising tool for assessing pain. The aim of this study was to assess if postoperative state after subcutaneous surgery affects HRV in dairy cows and to determine whether this could be modulated by NSAID. Nine cows were inserted with an implantable electrocardiograph logger. Cows were divided into the NSAID treatment group and the control group. The cows in the NSAID group had higher HRV than the control group, indicating a higher sympathetic activity in control animals, most likely due to untreated post-operative pain. Besides the ethical need for treating pain in production animals, ongoing pain has an adverse effect on animal productivity. Thus post-operative pain alleviation is recommended.
Effects of chronic mastitis and its treatment with ketoprofen on the milk ejection curve
Authors: Zecconi Alfonso , Frosi Samuele , Cipolla Micaela , Gusmara Claudia
Published: February 2018

In this Research Communication we report the results of a controlled study conducted under field conditions in which we analysed milk ejection curves in cows with chronic mastitis, and assessed the influence of antinflammatory treatment with ketoprofen. Total milking time was reduced in chronic mastitis cows, irrespective of ketoprofen treatment, and the proportion of bimodal flow curves was increased. This latter effect was partially reversed by ketoprofen. To our knowledge, this is the first study showing that chronic mastitis has a significant effect on the milk ejection curve. Antinflammatory treatment with ketoprofen was shown to be efficacious in reducing these negative effects, re-establishing a pattern close to the one observed in healthy cows.
SYSTEMATIC REVIEW WITH NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS OF ROTATOR CUFF TEAR TREATMENT
Authors: Kim Seihee , Hwang Jinseub , Kim Min Jee , Lim Jae-Young , Lee Woo Hyung , Choi Ji Eun
Published: February 2018

Objectives:Rotator cuff tear is the leading cause of the decline in quality of life for older adults, but comparative evidence on treatment effectiveness is lacking. This study systematically reviewed the effects of various rotator cuff tear treatments through a Bayesian meta-analysis of the related randomized clinical trials (RCTs).

Methods:We searched nine electronic databases for RCTs evaluating rotator cuff tear treatments from their inception through June 2017. A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the National Institute for Health and Care Excellence-Decision Support Unit guidelines (Supplementary Table 1). Outcomes included functional improvement, pain one year after surgical treatment, and tendon structural integrity. The Bayesian network meta-analysis was applied for functional improvement and pain, based on an assumption of consistency and similarity. Tendon integrity was reported descriptively.

Results:Fifteen RCTs were selected. Patients undergoing physiotherapy after open surgery showed statistically significant functional improvements compared with those undergoing physiotherapy only (mean differences, 9.1 [credible interval, 0.9–17.4]). Open surgery with physiotherapy was associated with a decrease in pain 1 year after treatment compared with when physiotherapy was combined with arthroscopic rotator cuff surgery, mini open surgery, platelet-rich plasma therapy, or physiotherapy alone (absolute value of mean difference 1.2 to 1.4). The tendon integrity results were inconsistent.

Conclusions:Some surgical treatments were associated with significant improvement in function and pain, but evidence regarding their comparative effectiveness is still lacking. A well-designed RCT discussing functional and structural treatment outcomes is needed in future.
A compact UWB band-pass filter with a notch band using multi-mode stub-loaded resonators (MM-SLR)
Authors: Karimi Gholamreza , Javidan Fatemeh , Salehi Amir Hossein
Published: February 2018

In this paper, an ultra-wideband (UWB) band-pass filter (BPF) with a sharp notch band is presented. The UWB BPF consists of modified elliptical-ring and multi-mode stub-loaded resonator (MM-SLR). By adding the asymmetric tight coupled lines resonator via input/output (I/O) lines, it can be achieved UWB band-pass response. With adding two bends to the middle resonator, a notch band at 6.86 GHz is created, so that it can be controlled using the mathematical formulas (MF). In the meantime, the equivalent circuit of the middle resonator is obtained using L–C analysis. Measured results of fabricated filter have the advantage such as ultra-wide pass band (flandfHof the defined UWB pass band are 3.776 and 10.42 GHz, which satisfy the requirements of FCC-specified UWB limits), compact size, low insertion loss <0.65 dB and the stop band of the proposed filter is from 11.1 to 16.32 GHz with attenuation of −39.8 to −42.14 dB, respectively. The proposed UWB filter is realized using the substrate with dielectric constant of 2.2 and substrate height of 0.787 mm. Experimental verification is provided and good agreement has been found between simulation and measurement results.
Decomposer food web in a deciduous forest shows high share of generalist microorganisms and importance of microbial biomass recycling
Authors: López-Mondéjar Ruben , Brabcová Vendula , Štursová Martina , Davidová Anna , Jansa Jan , Cajthaml Tomaš , Baldrian Petr
Published: February 2018

Forest soils represent important terrestrial carbon (C) pools where C is primarily fixed in the plant-derived biomass but it flows further through the biomass of fungi and bacteria before it is lost from the ecosystem as CO2 or immobilized in recalcitrant organic matter. Microorganisms are the main drivers of C flow in forests and play critical roles in the C balance through the decomposition of dead biomass of different origins. Here, we track the path of C that enters forest soil by following respiration, microbial biomass production, and C accumulation by individual microbial taxa in soil microcosms upon the addition of 13C-labeled biomass of plant, fungal, and bacterial origin. We demonstrate that both fungi and bacteria are involved in the assimilation and mineralization of C from the major complex sources existing in soil. Decomposer fungi are, however, better suited to utilize plant biomass compounds, whereas the ability to utilize fungal and bacterial biomass is more frequent among bacteria. Due to the ability of microorganisms to recycle microbial biomass, we suggest that the decomposer food web in forest soil displays a network structure with loops between and within individual pools. These results question the present paradigms describing food webs as hierarchical structures with unidirectional flow of C and assumptions about the dominance of fungi in the decomposition of complex organic matter.
Hints on ATGL implications in cancer: beyond bioenergetic clues
Authors: Vegliante Rolando , Di Leo Luca , Ciccarone Fabio , Ciriolo Maria Rosa
Published: February 2018

Among metabolic rearrangements occurring in cancer cells, lipid metabolism alteration has become a hallmark, aimed at sustaining accelerated proliferation. In particular, fatty acids (FAs) are dramatically required by cancer cells as signalling molecules and membrane building blocks, beyond bioenergetics. Along with de novo biosynthesis, free FAs derive from dietary sources or from intracellular lipid droplets, which represent the storage of triacylglycerols (TAGs). Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme of lipolysis, catalysing the first step of intracellular TAGs hydrolysis in several tissues. However, the roles of ATGL in cancer are still neglected though a putative tumour suppressor function of ATGL has been envisaged, as its expression is frequently reduced in different human cancers (e.g., lung, muscle, and pancreas). In this review, we will introduce lipid metabolism focusing on ATGL functions and regulation in normal cell physiology providing also speculative perspectives on potential non-energetic functions of ATGL in cancer. In particular, we will discuss how ATGL is implicated, mainly through the peroxisome proliferator-activated receptor-α (PPAR-α) signalling, in inflammation, redox homoeostasis and autophagy, which are well-known processes deregulated during cancer formation and/or progression.
DZNep inhibits H3K27me3 deposition and delays retinal degeneration in the rd1 mice
Authors: Zheng Shijie , Xiao Lirong , Liu Yu , Wang Yujiao , Cheng Lin , Zhang Junjun , Yan Naihong , Chen Danian
Published: February 2018

Retinitis pigmentosa (RP) is a group of inherited retinal degenerative diseases causing progressive loss of photoreceptors. Numerous gene mutations are identified to be related with RP, but epigenetic modifications may also be involved in the pathogenesis. Previous studies suggested that both DNA methylation and histone acetylation regulate photoreceptor cell death in RP mouse models. However, the role of histone methylation in RP has never been investigated. In this study, we found that trimethylation of several lysine sites of histone H3, including lysine 27 (H3K27me3), increased in the retinas of rd1 mice. Histone methylation inhibitor DZNep significantly reduced the calpain activity, delayed the photoreceptor loss, and improved ERG response of rd1 retina. RNA-sequencing indicated that DZNep synergistically acts on several molecular pathways that regulate photoreceptor survival in rd1 retina, including PI3K-Akt and photoreceptor differentiation pathways, revealing the therapeutic potential of DZNep for RP treatment. PI3K-Akt pathway and H3K27me3 form a feedback loop in rd1 retina, thus PI3K inhibitor LY294002 reduces phosphorylation of Ezh2 at serine 21 and enhances H3K27me3 deposition, and inhibiting H3K27me3 by DZNep can activate PI3K-Akt pathway by de-repressing gene expression of PI3K subunits Pik3r1 and Pik3r3. These findings suggest that histone methylation, especially H3K27me3 deposition is a novel mechanism and therapeutic target for retinal degenerative diseases, similar to H3K27me3-mediated ataxia-telangiectasia in Atm
−/−
mouse.
Recent progress and perspectives of space electric propulsion systems based on smart nanomaterials
Authors: Levchenko I. , Xu S. , Teel G. , Mariotti D. , Walker M. L. R. , Keidar M.
Published: February 2018

Drastic miniaturization of electronics and ingression of next-generation nanomaterials into space technology have provoked a renaissance in interplanetary flights and near-Earth space exploration using small unmanned satellites and systems. As the next stage, the NASA’s 2015 Nanotechnology Roadmap initiative called for new design paradigms that integrate nanotechnology and conceptually new materials to build advanced, deep-space-capable, adaptive spacecraft. This review examines the cutting edge and discusses the opportunities for integration of nanomaterials into the most advanced types of electric propulsion devices that take advantage of their unique features and boost their efficiency and service life. Finally, we propose a concept of an adaptive thruster.
Unattached kinetochores drive their own capturing by sequestering a CLASP
Authors: Kolenda Caroline , Ortiz Jennifer , Pelzl Marina , Norell Sarina , Schmeiser Verena , Lechner Johannes
Published: February 2018

Kinetochores that are not attached to microtubules prevent chromosome missegregation via the spindle assembly checkpoint. We show that they also promote their own capturing. Similar to what governs the localization of spindle assembly checkpoint proteins, the phosphorylation of Spc105 by Mps1 allows unattached kinetochores to sequester Stu1 in cooperation with Slk19. The withdrawal of Stu1, a CLASP essential for spindle integrity, from microtubules and attached kinetochores disrupts the organization of the spindle and thus allows the enhanced formation of dynamic random microtubules that span the nucleus and are ideal to capture unattached kinetochores. The enhanced formation of nuclear random microtubules does not occur if Stu1 sequestering to unattached kinetochores fails and the spindle remains uncompromised. Consequently, these cells exhibit a severely decreased capturing efficiency. After the capturing event, Stu1 is relocated to the capturing microtubule and prevents precocious microtubule depolymerization as long as kinetochores are laterally or incompletely end-on attached.
Aggregating sequences that occur in many proteins constitute weak spots of bacterial proteostasis
Authors: Khodaparast Ladan , Khodaparast Laleh , Gallardo Rodrigo , Louros Nikolaos N. , Michiels Emiel , Ramakrishnan Reshmi , Ramakers Meine , Claes Filip , Young Lydia , Shahrooei Mohammad , Wilkinson Hannah , Desager Matyas , Mengistu Tadesse Wubishet , Nilsson K. Peter R. , Hammarström Per , Aertsen Abram , Carpentier Sebastien , Van Eldere Johan , Rousseau Frederic , Schymkowitz Joost
Published: February 2018

Aggregation is a sequence-specific process, nucleated by short aggregation-prone regions (APRs) that can be exploited to induce aggregation of proteins containing the same APR. Here, we find that most APRs are unique within a proteome, but that a small minority of APRs occur in many proteins. When aggregation is nucleated in bacteria by such frequently occurring APRs, it leads to massive and lethal inclusion body formation containing a large number of proteins. Buildup of bacterial resistance against these peptides is slow. In addition, the approach is effective against drug-resistant clinical isolates ofEscherichiacoliandAcinetobacterbaumannii, reducing bacterial load in a murine bladder infection model. Our results indicate that redundant APRs are weak points of bacterial protein homeostasis and that targeting these may be an attractive antibacterial strategy.
Photosystem II Subunit S overexpression increases the efficiency of water use in a field-grown crop
Authors: Głowacka Katarzyna , Kromdijk Johannes , Kucera Katherine , Xie Jiayang , Cavanagh Amanda P. , Leonelli Lauriebeth , Leakey Andrew D. B. , Ort Donald R. , Niyogi Krishna K. , Long Stephen P.
Published: February 2018

Insufficient water availability for crop production is a mounting barrier to achieving the 70% increase in food production that will be needed by 2050. One solution is to develop crops that require less water per unit mass of production. Water vapor transpires from leaves through stomata, which also facilitate the influx of CO2during photosynthetic assimilation. Here, we hypothesize thatPhotosystem II Subunit S(PsbS) expression affects a chloroplast-derived signal for stomatal opening in response to light, which can be used to improve water-use efficiency. Transgenic tobacco plants with a range ofPsbSexpression, from undetectable to 3.7 times wild-type are generated. Plants with increasedPsbSexpression show less stomatal opening in response to light, resulting in a 25% reduction in water loss per CO2assimilated under field conditions. Since the role of PsbS is universal across higher plants, this manipulation should be effective across all crops.
Highly stretchable carbon aerogels
Authors: Guo Fan , Jiang Yanqiu , Xu Zhen , Xiao Youhua , Fang Bo , Liu Yingjun , Gao Weiwei , Zhao Pei , Wang Hongtao , Gao Chao
Published: February 2018

Carbon aerogels demonstrate wide applications for their ultralow density, rich porosity, and multifunctionalities. Their compressive elasticity has been achieved by different carbons. However, reversibly high stretchability of neat carbon aerogels is still a great challenge owing to their extremely dilute brittle interconnections and poorly ductile cells. Here we report highly stretchable neat carbon aerogels with a retractable 200% elongation through hierarchical synergistic assembly. The hierarchical buckled structures and synergistic reinforcement between graphene and carbon nanotubes enable a temperature-invariable, recoverable stretching elasticity with small energy dissipation (~0.1, 100% strain) and high fatigue resistance more than 106 cycles. The ultralight carbon aerogels with both stretchability and compressibility were designed as strain sensors for logic identification of sophisticated shape conversions. Our methodology paves the way to highly stretchable carbon and neat inorganic materials with extensive applications in aerospace, smart robots, and wearable devices.
Coupling between intra- and intermolecular motions in liquid water revealed by two-dimensional terahertz-infrared-visible spectroscopy
Authors: Grechko Maksim , Hasegawa Taisuke , D’Angelo Francesco , Ito Hironobu , Turchinovich Dmitry , Nagata Yuki , Bonn Mischa
Published: February 2018

The interaction between intramolecular and intermolecular degrees of freedom in liquid water underlies fundamental chemical and physical phenomena such as energy dissipation and proton transfer. Yet, it has been challenging to elucidate the coupling between these different types of modes. Here, we report on the direct observation and quantification of the coupling between intermolecular and intramolecular coordinates using two-dimensional, ultra-broadband, terahertz-infrared-visible (2D TIRV) spectroscopy and molecular dynamics calculations. Our study reveals strong coupling of the O-H stretch vibration, independent of the degree of delocalization of this high-frequency mode, to low-frequency intermolecular motions over a wide frequency range from 50 to 250 cm−1, corresponding to both the intermolecular hydrogen bond bending (≈ 60 cm−1) and stretching (≈ 180 cm−1) modes. Our results provide mechanistic insights into the coupling of the O-H stretch vibration to collective, delocalized intermolecular modes.
Eye movement patterns in infants suggest illusory motion perception induced by stationary gradation
Authors: Matsushita Soyogu , Sato Kazuki , Murakami Kosuke , Tsurumi Shuma , Kanazawa So , Yamaguchi Masami K.
Published: February 2018

Infants less than 1 year old are known to preferentially look at pictures of motion illusion induced by luminance gradation. However, the mechanisms underlying infant’s perception of motion illusion remain unclear. The current study analyzed the eye movement patterns of infants perceiving a motion illusion induced by stationary luminance gradations (a derivative of the Fraser-Wilcox illusion). Infants produced the same movement patterns that increase the magnitude of illusory motion in adults. We conclude that infants and adults similarly perceive motion illusion.
Stromal C-type lectin receptor COLEC12 integrates H. pylori, PGE2-EP2/4 axis and innate immunity in gastric diseases
Authors: Chang Lin-Li , Hsu Wen-Hung , Kao Mou-Chieh , Chou Chih-Chung , Lin Chung-Cheng , Liu Chung-Jung , Weng Bi-Chuang , Kuo Fu-Chen , Kuo Chao-Hung , Lin Ming-Hong , Wang Chun-Jen , Lin Chun-Hung , Wu Deng-Chyang , Huang Shau-Ku
Published: February 2018

Tissue stroma is known to be important in regulating Hp-mediated inflammation, but its interaction with Hp and dendritic cells (DCs) remains to be determined. To this end, the potential crosstalk between H. pylori (Hp) infected gastric stromal cells (Hp-GSCs) and DCs was investigated. Primary GSCs from cancerous and adjacent normal tissues were generated from gastric cancer patients, and monocyte-derived DCs were obtained from healthy individuals. Levels of cytokines and prostaglandin E2 (PGE2) were measured by ELISA, and C-type lectin expression in GSCs was assessed by flow cytometry and immunohistochemistry. In a trans-well co-culture system, significantly upregulated DC-derived IL-23 expression was found when DCs were co-cultured with Hp-infected GSCs (Hp-GSCs). Further, PGE2 from Hp-GSCs was discovered to possess the priming effect, which could be inhibited by anti-COLEC12 (Collectin subfamily member 12) Abs, COLEC12 knockdown or when alpha3-fucosyltransferase-null (futB; HP0651) strain of Hp was used. Also, the expression of COLEC12 was co-localized with CD90+ stromal cells in cancerous tissues. Hp-GSCs-conditioned DCs were able to induce the expression of IL-17 from CD4+ T cells, which could be inhibited by IL-23-neutralizing Abs. These results suggested the importance of COLEC12 as a receptor involved in Hp-stromal cell interaction and its subsequent conditioning effect on DCs.
Comprehensive Review of Genetic Association Studies and Meta-Analysis on polymorphisms in microRNAs and Urological Neoplasms Risk
Authors: Zhang Ligang , Zhang Meng , Wang Hao , Wang Yangyang , Zhou Jun , Hao Zongyao , Zhang Li , Liang Chaozhao
Published: February 2018

Gene expression is negatively regulated by microRNAs (miRNAs), which commonly act as tumor oncogenes or suppressors. Previous results were inconsistent concerning the relationship between polymorphisms in miRNAs and risk of urological neoplasms. Here, we conducted a comprehensive literature research on diverse databases aiming at enrolling all eligible studies up to August 31, 2016. A total of 13 publications comprising 29 case-control studies were enrolled for three polymorphisms in three miRNAs. Overall analyses suggested significant associations between miR-146a rs2910164 polymorphism and urological neoplasms risk in allelic, homozygote and recessive models. In the stratified analysis by ethnicity, we uncovered a significant association between rs2910164 polymorphism and risk of urological neoplasms in Asian populations in allelic, homozygote and recessive models. Highlighted, when stratified analysis was conducted by cancer type, rs2910164 polymorphism was also significantly associated with an increased risk of bladder cancer in allelic, homozygote and recessive models. Although for rs11614913 and rs3746444 polymorphisms, overall analyses suggested negative results, for rs11614913 polymorphism, when subgroup analysis was conducted by cancer type, a significantly decreased risk of renal cell cancer was identified in recessive model. In brief, current work indicated that miR-146a rs2910164 polymorphism is a risk factor for urological neoplasms, particularly for bladder cancer.
Bacterial reduction in sealed caries lesions is strain- and material-specific
Authors: Marggraf Teresa , Ganas Petra , Paris Sebastian , Schwendicke Falk
Published: February 2018

Sealing can arrest caries lesions. We aimed to evaluate if sealing effects and kinetics are bacterial-strain and sealing-material specific. Human dentin discs were mounted in a dual-chamber device. Caries lesions were induced chemically and contaminated with either Lactobacillus rhamnosus (LR) or Streptococcus sobrinus (SS). For (1) kinetics assessment, the initial bacterial load and the sealing period were varied, and lesions sealed using a self-etch adhesive and composite. For (2) comparing materials, six sealing protocols (#1-#6) were evaluated: 1# Self-etch adhesive plus composite placed without a liner, or #2 calcium hydroxide, or #3 mineral trioxide aggregate, or #4 Biodentine liners; #5 antibacterial adhesive plus composite; #6 glass ionomer cement. Pulpal fluid flow was simulated during sealing. The outcome was the number of surviving bacteria (CFU) per g dentin. For LR, bacterial survival increased significantly with increasing initial bacterial load and decreased with longer sealing periods. The relative reduction followed a first-order kinetics. More LR survived under calcium hydroxide or MTA than other materials (p < 0.001). For SS, nearly no bacteria survived sealing regardless of sealing period, initial bacterial load or sealing material. In conclusion, sealing effects and kinetics were strain- and material-specific.
Acquired Enamel Pellicle Engineered Peptides: Effects on Hydroxyapatite Crystal Growth
Authors: Valente Maria Teresa , Moffa Eduardo Buozi , Crosara Karla Tonelli Bicalho , Xiao Yizhi , de Oliveira Thais Marchini , Machado Maria Aparecida de Andrade Moreira , Siqueira Walter Luiz
Published: February 2018

The aim of this study was to test the hypothesis that duplication/hybridization of functional domains of naturally occurring pellicle peptides amplified the inhibitory effect of hydroxyapatite crystal growth, which is related to enamel remineralization and dental calculus formation. Histatin 3, statherin, their functional domains (RR14 and DR9), and engineered peptides (DR9-DR9 and DR9-RR14) were tested at seven different concentrations to evaluate the effect on hydroxyapatite crystal growth inhibition. A microplate colorimetric assay was used to quantify hydroxyapatite crystal growth. The half-maximal inhibitory concentration (IC50) was determined for each group. ANOVA and Student-Newman-Keuls pairwise comparisons were used to compare the groups. DR9-DR9 increased the inhibitory effect of hydroxyapatite crystal growth compared to single DR9 (p < 0.05), indicating that functional domain multiplication represented a strong protein evolution pathway. Interestingly, the hybrid peptide DR9-RR14 had an intermediate inhibitory effect compared to DR9 and DR9-DR9. This study used an engineered peptide approach to investigate a potential evolution protein pathway related to duplication/hybridization of acquired enamel pellicle’s natural peptide constituents, contributing to the development of synthetic peptides for therapeutic use against dental caries and periodontal disease.
Adult mouse eIF2Bε Arg191His astrocytes display a normal integrated stress response in vitro
Authors: Wisse Lisanne E. , ter Braak Timo J. , van de Beek Malu-Clair , van Berkel Carola G. M. , Wortel Joke , Heine Vivi M. , Proud Chris G. , van der Knaap Marjo S. , Abbink Truus E. M.
Published: February 2018

Vanishing white matter (VWM) is a genetic childhood white matter disorder, characterized by chronic as well as episodic, stress provoked, neurological deterioration. Treatment is unavailable and patients often die within a few years after onset. VWM is caused by recessive mutations in the eukaryotic initiation factor 2B (eIF2B). eIF2B regulates protein synthesis rates in every cell of the body. In normal cells, various types of cellular stress inhibit eIF2B activity and induce the integrated stress response (ISR). We have developed a VWM mouse model homozygous for the pathogenic Arg191His mutation in eIF2Bε (2b5
ho
), representative of the human disease. Neuropathological examination of VWM patient and mouse brain tissue suggests that astrocytes are primarily affected. We hypothesized that VWM astrocytes are selectively hypersensitive to ISR induction, resulting in a heightened response. We cultured astrocytes from wildtype and VWM mice and investigated the ISR in assays that measure transcriptional induction of stress genes, protein synthesis rates and cell viability. We investigated the effects of short- and long-term stress as well as stress recovery. We detected congruent results amongst the various assays and did not detect a hyperactive ISR in VWM mouse astrocytes.
Multimorbidity patterns in relation to polypharmacy and dosage frequency: a nationwide, cross-sectional study in a Japanese population
Authors: Aoki Takuya , Yamamoto Yosuke , Ikenoue Tatsuyoshi , Onishi Yoshihiro , Fukuhara Shunichi
Published: February 2018

In the present study, we aimed to identify multimorbidity patterns in a Japanese population and investigate whether these patterns have differing effects on polypharmacy and dosage frequency. Data was collected on 17 chronic health conditions via nationwide cross-sectional survey of 3,256 adult Japanese residents. Factor analysis was performed to identify multimorbidity patterns, and associations were determined with excessive polypharmacy [concurrent use of ≥ 10 prescription or over-the-counter (OTC) medications] and higher dosage frequency ( ≥ 3 doses per day). Secondary outcomes were the number of concurrent prescription medications and the number of concurrent OTC medications. We used a generalized linear model to adjust for individual sociodemographic characteristics. Five multimorbidity patterns were identified: cardiovascular/renal/metabolic, neuropsychiatric, skeletal/articular/digestive, respiratory/dermal, and malignant/digestive/urologic. Among these patterns, malignant/digestive/urologic and cardiovascular/renal/metabolic patterns showed the strongest associations with excessive polypharmacy and the number of concurrent OTC medications. Malignant/digestive/urologic, respiratory/dermal, and skeletal/articular/digestive patterns were also associated with higher dosage frequency. Multimorbidity patterns have differing effects on excessive polypharmacy and dosage frequency. Malignant/digestive/urologic pattern may be at higher risk of impaired medication safety and increased treatment burden, than other patterns. Continued study is warranted to determine how to incorporate multimorbidity patterns into risk assessments of polypharmacy and overall treatment burden.
Development and Evaluation of Novel Statistical Methods in Urine Biomarker-Based Hepatocellular Carcinoma Screening
Authors: Wang Jeremy , Jain Surbhi , Chen Dion , Song Wei , Hu Chi-Tan , Su Ying-Hsiu
Published: February 2018

Hepatocellular carcinoma is one of the fastest growing cancers in the US and has a low survival rate, partly due to difficulties in early detection. Because of HCC’s high heterogeneity, it has been suggested that multiple biomarkers would be needed to develop a sensitive HCC screening test. This study applied random forest (RF), a machine learning technique, and proposed two novel models, fixed sequential (FS) and two-step (TS), for comparison with two commonly used statistical techniques, logistic regression (LR) and classification and regression trees (CART), in combining multiple urine DNA biomarkers for HCC screening using biomarker values obtained from 137 HCC and 431 non-HCC (224 hepatitis and 207 cirrhosis) subjects. The sensitivity, specificity, area under the receiver operating curve, and variability were estimated through repeated 10-fold cross-validation to compare the models’ performances in accuracy and robustness. We show that RF and TS have higher accuracy and stability; specifically, they reach 90% specificity and 86%/87% sensitivity respectively along with 15% higher sensitivity and 10% higher specificity than LR in cross-validation. The potential of RF and TS to develop a panel of multiple biomarkers and the possibility for self-training, cloud-based models for HCC screening are discussed.
Dietary n-3 and n-6 polyunsaturated fatty acids, the FADS gene, and the risk of gastric cancer in a Korean population
Authors: Lee Sunghee , Lee Jeonghee , Choi Il Ju , Kim Young-Woo , Ryu Keun Won , Kim Young-Il , Kim Jeongseon
Published: February 2018

n-3 polyunsaturated fatty acids (PUFAs) and n-6 PUFAs are reported to have immunomodulatory effects, but few studies have examined these functions. Thus, we examined whether dietary n-3 and n-6 PUFAs are associated with the risk of gastric cancer and further investigated whether fatty acid desaturases 1 and 2 (FADS1 and FADS2) modify this association. In a case-control study, 1,464 participants (402 cases and 1,062 controls) were enrolled. A semi-quantitative food frequency questionnaire was utilized to measure dietary PUFA intake. Genotyping was performed using the Axiom® Exome 319 Array. Multivariable logistic models were established after adjusting for confounding variables. The risk of gastric cancer was significantly decreased among participants who had the highest tertile intake of docosahexaenoic acid (DHA), an n-3 PUFA, even after adjusting for covariates [odds ratios (OR) = 0.72, 95% confidence intervals (95% CIs) = 0.53–0.99]. However, no significant interaction according to FADS1 rs174546 or FADS2 rs174583 was observed. In conclusion, we observed a significant inverse association between dietary DHA and the risk of gastric cancer but found that FADS1 rs174546 and FADS2 rs174583 did not modify the association between dietary n-3 or n-6 PUFAs and gastric cancer risk.
Estimating apple tree canopy chlorophyll content based on Sentinel-2A remote sensing imaging
Authors: Li Cheng , Zhu Xicun , Wei Yu , Cao Shujing , Guo Xiaoyan , Yu Xinyang , Chang Chunyan
Published: February 2018

The remote sensing technology provides a new means for the determination of chlorophyll content in apple trees that includes a rapid analysis, low cost and large monitoring area. The Back-Propagation Neural Network (BPNN) and the Supported Vector Machine Regression (SVMR) methods were both frequently used method to construct estimation model based on remote sensing imaging. The aim of this study was to find out which estimation model of apple tree canopy chlorophyll content based on the vegetation indices constructed with visible, red edge and near-infrared bands of the sensor of Sentinel-2 was more accurate and stabler. The results were as follows: The calibration set coefficient of determination (R2) value of 0.729 and validation set R2 value of 0.667 of the model using the SVMR method based on the vegetation indices (NDVIgreen + NDVIred + NDVIre) were higher than those of the model using the BPNN method by 8.2% and 11.0%, respectively. The calibration set root mean square error (RMSE) of 0.159 and validation set RMSE of 0.178 of the model using the SVMR method based on the vegetation indices (NDVIgreen + NDVIred + NDVIre) were lower than those of the model using the BPNN method by 5.9% and 3.8%, respectively.
A symbolic network-based nonlinear theory for dynamical systems observability
Authors: Letellier Christophe , Sendiña-Nadal Irene , Bianco-Martinez Ezequiel , Baptista Murilo S.
Published: February 2018

When the state of the whole reaction network can be inferred by just measuring the dynamics of a limited set of nodes the system is said to be fully observable. However, as the number of all possible combinations of measured variables and time derivatives spanning the reconstructed state of the system exponentially increases with its dimension, the observability becomes a computationally prohibitive task. Our approach consists in computing the observability coefficients from a symbolic Jacobian matrix whose elements encode the linear, nonlinear polynomial or rational nature of the interaction among the variables. The novelty we introduce in this paper, required for treating large-dimensional systems, is to identify from the symbolic Jacobian matrix the minimal set of variables (together with their time derivatives) candidate to be measured for completing the state space reconstruction. Then symbolic observability coefficients are computed from the symbolic observability matrix. Our results are in agreement with the analytical computations, evidencing the correctness of our approach. Its application to efficiently exploring the dynamics of real world complex systems such as power grids, socioeconomic networks or biological networks is quite promising.
Egr2-dependent microRNA-138 is dispensable for peripheral nerve myelination
Authors: Lin Hsin-Pin , Oksuz Idil , Svaren John , Awatramani Rajeshwar
Published: February 2018

Recent studies have elucidated the crucial role for microRNAs in peripheral nerve myelination by ablating components of the microRNA synthesis machinery. Few studies have focused on the role of individual microRNAs. To fill this gap, we focused this study on miR-138, which was shown to be drastically reduced in Dicer1 and Dgcr8 knockout mice with hypomyelinating phenotypes and to potentially target the negative regulators of Schwann cell differentiation. Here, we show that of two miR-138 encoding loci, mir-138-1 is the predominant locus transcribed in Schwann cells. mir-138-1 is transcriptionally upregulated during myelination and downregulated upon nerve injury. EGR2 is required for mir-138-1 transcription during development, and both SOX10 and EGR2 bind to an active enhancer near the mir-138-1 locus. Based on expression analyses, we hypothesized that miR-138 facilitates the transition between undifferentiated Schwann cells and myelinating Schwann cells. However, in conditional knockouts, we could not detect significant changes in Schwann cell proliferation, cell cycle exit, or myelination. Overall, our results demonstrate that miR-138 is an Egr2-dependent microRNA but is dispensable for Schwann cell myelination.
Expanding biological space coverage enhances the prediction of drug adverse effects in human using in vitro activity profiles
Authors: Huang Ruili , Xia Menghang , Sakamuru Srilatha , Zhao Jinghua , Lynch Caitlin , Zhao Tongan , Zhu Hu , Austin Christopher P. , Simeonov Anton
Published: February 2018

In vitro assay data have recently emerged as a potential alternative to traditional animal toxicity studies to aid in the prediction of adverse effects of chemicals on humans. Here we evaluate the data generated from a battery of quantitative high-throughput screening (qHTS) assays applied to a large and diverse collection of chemicals, including approved drugs, for their capacity in predicting human toxicity. Models were built with animal in vivo toxicity data, in vitro human cell-based assay data, as well as in combination with chemical structure and/or drug-target information to predict adverse effects observed for drugs in humans. Interestingly, we found that the models built with the human cell-based assay data performed close to those of the models based on animal in vivo toxicity data. Furthermore, expanding the biological space coverage of assays by including additional drug-target annotations was shown to significantly improve model performance. We identified a small set of targets, which, when added to the current suite of in vitro human cell-based assay data, result in models that greatly outperform those built with the existing animal toxicity data. Assays can be developed for this set of targets to screen compounds for construction of robust models for human toxicity prediction.
Femtosecond Laser Mass Spectrometry and High Harmonic Spectroscopy of Xylene Isomers
Authors: Alharbi Abdullah , Boguslavskiy Andrey E. , Austin Dane , Thiré Nicolas , Wood D. , Hawkins P. , McGrath Felicity , Johnson A. S. , Lopez-Quintas I. , Schmidt Bruno , Légaré Francois , Marangos J. P. , Le Anh-Thu , Bhardwaj Ravi
Published: February 2018

Structural isomers, molecules having the same chemical formula but with atoms bonded in different order, are hard to identify using conventional spectroscopy and mass spectrometry. They exhibit virtually indistinguishable mass spectra when ionized by electrons. Laser mass spectrometry based on photoionization of the isomers has emerged as a promising alternative but requires shaped ultrafast laser pulses. Here we use transform limited femtosecond pulses to distinguish the isomers using two methods. First, we probe doubly charged parent ions with circularly polarized light. We show that the yield of doubly charged ortho-xylene decreases while para-xylene increases over a range of laser intensities when the laser polarization is changed from linear to circular. Second, we probe high harmonic generation from randomly oriented isomer molecules subjected to an intense laser field. We show that the yield of high-order harmonics varies with the positioning of the methyl group in xylene isomers (ortho-, para- and meta-) and is due to differences in the strength of tunnel ionization and the overlap between the angular peaks of ionization and photo-recombination.
Dynamical Casimir Effect for Gaussian Boson Sampling
Authors: Peropadre Borja , Huh Joonsuk , Sabín Carlos
Published: February 2018

We show that the Dynamical Casimir Effect (DCE), realized on two multimode coplanar waveg-uide resonators, implements a gaussian boson sampler (GBS). The appropriate choice of the mirror acceleration that couples both resonators translates into the desired initial gaussian state and many-boson interference in a boson sampling network. In particular, we show that the proposed quantum simulator naturally performs a classically hard task, known as scattershot boson sampling. Our result unveils an unprecedented computational power of DCE, and paves the way for using DCE as a resource for quantum simulation.
I-AbACUS: a Reliable Software Tool for the Semi-Automatic Analysis of Invasion and Migration Transwell Assays
Authors: Cortesi Marilisa , Llamosas Estelle , Henry Claire E. , Kumaran Raani-Yogeeta A. , Ng Benedict , Youkhana Janet , Ford Caroline E.
Published: February 2018

The quantification of invasion and migration is an important aspect of cancer research, used both in the study of the molecular processes involved in this collection of diseases and the evaluation of the efficacy of new potential treatments. The transwell assay, while being one of the most widely used techniques for the evaluation of these characteristics, shows a high dependence on the operator’s ability to correctly identify the cells and a low protocol standardization. Here we present I-AbACUS, a software tool specifically designed to aid the analysis of transwell assays that automatically and specifically recognizes cells in images of stained membranes and provides the user with a suggested cell count. A complete description of this instrument, together with its validation against the standard analysis technique for this assay is presented. Furthermore, we show that I-AbACUS is versatile and able to elaborate images containing cells with different morphologies and that the obtained results are less dependent on the operator and their experience. We anticipate that this instrument, freely available (Gnu Public Licence GPL v2) at www.marilisacortesi.com as a standalone application, could significantly improve the quantification of invasion and migration of cancer cells.
Social content and emotional valence modulate gaze fixations in dynamic scenes
Authors: Rubo Marius , Gamer Matthias
Published: February 2018

Previous research has shown that low-level visual features (i.e., low-level visual saliency) as well as socially relevant information predict gaze allocation in free viewing conditions. However, these studies mainly used static and highly controlled stimulus material, thus revealing little about the robustness of attentional processes across diverging situations. Secondly, the influence of affective stimulus characteristics on visual exploration patterns remains poorly understood. Participants in the present study freely viewed a set of naturalistic, contextually rich video clips from a variety of settings that were capable of eliciting different moods. Using recordings of eye movements, we quantified to what degree social information, emotional valence and low-level visual features influenced gaze allocation using generalized linear mixed models. We found substantial and similarly large regression weights for low-level saliency and social information, affirming the importance of both predictor classes under ecologically more valid dynamic stimulation conditions. Differences in predictor strength between individuals were large and highly stable across videos. Additionally, low-level saliency was less important for fixation selection in videos containing persons than in videos not containing persons, and less important for videos perceived as negative. We discuss the generalizability of these findings and the feasibility of applying this research paradigm to patient groups.