bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA Methylation of Candidate Genes (ACE II, IFN-γ, AGTR 1, CKG, ADD1, SCNN1B and TLR2) in Essential Hypertension: A Systematic Review and Quantitative Evidence Synthesis
Authors: Holmes Laurens , Lim Andrew , Comeaux Camillia R. , Dabney Kirk W. , Okundaye Osatohamwen
Published: December 2019

Physical, chemical, and social environments adversely affect the molecular process and results in cell signal transduction and the subsequent transcription factor dysregulation, leading to impaired gene expression and abnormal protein synthesis. Stressful environments such as social adversity, isolation, sustained social threats, physical inactivity, and highly methylated diets predispose individuals to molecular level alterations such as aberrant epigenomic modulations that affect homeostasis and hemodynamics. With cardiovascular disease as the leading cause of mortality in the US and blacks/African Americans being disproportionately affected by hypertension (HTN) which contributes substantially to these deaths, reflecting the excess mortality and survival disadvantage of this sub-population relative to whites, understanding the molecular events, including epigenomic and socio-epigenomic modulations, is relevant to narrowing the black-white mortality risk differences. We aimed to synthesize epigenomic findings in HTN namely (a) angiotensin-converting enzyme 2 (ACE II) gene, (b) Toll-like receptor 2 (TLR2) gene, (c) interferon γ (IFN-γ) gene, and (d) Capping Actin Protein, Gelosin-Like (CAPG) gene, adducin 1(ADD1) gene, (e) Tissue inhibitor of metalloproteinase 3 (TIMP3), (f) mesoderm specific transcript (MEST) loci, (g) sodium channel epithelial 1 alpha subunit 2 (SCNN1B), (h) glucokinase (CKG) gene (i) angiotensin II receptor, type1 (AGTR1), and DNA methylation (mDNA). A systematic review and quantitative evidence synthesis (QES) was conducted using Google Scholar and PubMed with relevant search terms. Data were extracted from studies on: (a) Epigenomic modulations in HTN based on ACE II (b) TLR2, (c) IFN-γ gene, (d) CAPG, ADD1, TIMP3, MEST loci, and mDNA. The random-effect meta-analysis method was used for a pooled estimate of the common effect size, while z statistic and I^2 were used for the homogeneity of the common effect size and between studies on heterogeneity respectively. Of the 642 studies identified, five examined hypermethylation while seven studies assessed hypomethylation in association with HTN. The hypermethylation of ACE II, SCNN1B, CKG, IFN-γ gene, and miR-510 promoter were associated with hypertension, the common effect size (CES) = 6.0%, 95% CI, −0.002–11.26. In addition, the hypomethylation of TLR2, IFN-γ gene, ADD1, AGTR1, and GCK correlated with hypertension, the CES = 2.3%, 95% CI, −2.51–7.07. The aberrant epigenomic modulation of ACE II, TLR2, IFN-γ, AGTR1, and GCK correlated with essential HTN. Transforming the environments resulting from these epigenomic lesions will facilitate early intervention mapping in reducing HTN in the US population, especially among socially disadvantaged individuals, particularly racial/ethnic minorities.
Cigarette Affordability and Cigarette Consumption among Adult and Elderly Chinese Smokers: Evidence from A Longitudinal Study
Authors: Hu Xiao , Wang Yang , Huang Jidong , Zheng Rong
Published: December 2019

China is in the midst of an epidemic of non-communicable diseases (NCDs), which has increasingly accounted for a growing share of disease burden, due in part to China’s ongoing rapid socioeconomic changes and population aging. Smoking, the second leading health risk factors associated with NCDs in China, disproportionately affects the old population more than their younger counterparts. Using survey data from the China Health and Retirement Longitudinal Study (CHARLS), this study evaluated the impact of changes in cigarette affordability on smoking behavior among middle-aged and elderly (age 45 and older) smokers. Self-reported cigarette price and disposable income were used to calculate cigarette affordability. Cigarette consumption was measured using the number of cigarettes smoked per day reported by the survey respondents. The correlation between cigarette affordability and cigarette consumption was estimated using generalized estimating equations adjusting for demographics, socioeconomic status, geolocations, and cigarette price tiers, as well as year fixed effects. The estimated overall conditional cigarette affordability elasticity of demand was –0.165, implying a 10% decrease in cigarette affordability would result in a reduction in cigarette consumption by 1.65%. The cigarette affordability responsiveness differs by demographics, socioeconomic status, geolocations, and cigarette price tiers. This study provides evidence that tax/price policies that reduce cigarette affordability could lead to a decrease in cigarette consumption among middle-aged and elderly smokers in China. Smoke-free laws, as well as minimum price regulations, may be needed to compliment excise tax policy to target specific smoking subgroups whose cigarette consumption is less sensitive to changes in cigarette affordability.
The Impact of PM10 Levels on Pedestrian Volume: Findings from Streets in Seoul, South Korea
Authors: Chung Juwon , Kim Seung-Nam , Kim Hyungkyoo
Published: December 2019

Although many studies have revealed that both air quality and walking activity are dominant contributors to public health, little is known about the relationship between them. Moreover, previous studies on this subject have given little consideration to the day-to-day atmospheric conditions and floating populations of surrounding areas even though most pedestrian count surveys are not conducted on a single day. Against this backdrop, using the 2015 Pedestrian Volume Survey data and quasi-real-time weather, air quality, and transit ridership data in Seoul, this study investigates the relationship between particulate matter (PM)10 and pedestrian street volumes empirically. The regression results suggest that PM10 concentration determines people’s intention to walk and affects the volume of street-level pedestrians. The three regression models, which adopted different spatial aggregation units of air quality, demonstrated that PM10 elasticity of pedestrian volume is the largest in the borough-level (the smallest spatial unit of air quality alert) model. This means that people react to the most accurate information they can access, implying that air quality information should be provided in smaller spatial units for public health. Thus, strengthening air quality warning standards of PM is an effective measure for enhancing public health.
The Role of Leisure-Time Physical Activity in the Change of Work-Related Stress (ERI) over Time
Authors: du Prel Jean-Baptist , Siegrist Johannes , Borchart Daniela
Published: December 2019

Background: Every second employee in Europe complains about work-related stress. Occupational stress due to an imbalance between efforts spent and rewards gained (effort-reward imbalance = ERI) is well investigated and it is associated with mental and physical health. A common guess is that leisure-time physical activity (LTPA) has beneficial effects on work-related stress. Yet, evidence in support of this assumption is weak, especially regarding ERI-stress. Longitudinal studies investigating the role of LTPA on ERI are missing. Therefore, this study aims to investigate the effect of LTPA on work-related stress by ERI over time. Methods: 3961 socially insured employees that were born in 1959 or 1965 and working in the first (t1: 2011) and second wave (t2: 2014) of the lidA-study were included. Work-related stress was measured by ERI, LTPA by the self-rated weekly frequency of physical activities. Besides the direct effect, a moderating effect of LTPA on ERI over time was tested in the multiple linear regression analysis. Results: The ERI at t1 was strongly associated with ERI at t2. While LTPA had no direct effect on ERI(t2), it was a significant moderator of ERI from t1 to t2: The higher the frequency of LTPA, the lower ERI was over time. This interaction of LTPA with ERI remained after adjustment for socio-demographic factors. Conclusions: The long-term moderating effect of LTPA on ERI is in agreement with former investigations on the role of LTPA on work-related stress, generally, and on its cross-sectional effect on ERI-stress, specifically. Some of Hill’s criteria of a causal association in epidemiology (biological gradient, temporality, consistency) support our findings. As LTPA has also been shown to exert a protective effect on health outcomes that are associated with ERI, the moderation of ERI by LTPA could partly explain this protective effect. Future observational and interventional studies are required to support our results over more than two age groups and study times.
Cultural Adaptation, Validation, and Analysis of the Self-Efficacy in Palliative Care Scale for Use with Spanish Nurses
Authors: Herrero-Hahn Raquel , Montoya-Juárez Rafael , Hueso-Montoro César , Martí-García Celia , Salazar-Blandón Diego Alejandro , García-Caro María Paz
Published: December 2019

The aim of the present study is to validate the Self-Efficacy in Palliative Care Scale (SEPC) in Spanish nursing professionals and students, to describe their levels of self-efficacy, and to determine the influencing factors. A validation study and a cross-sectional descriptive study were carried out, with the data analysed using contrast tests and multiple linear regression; 552 nurses and 440 nursing students participated. The Spanish version consists of 23 items and has a high degree of reliability (α = 0.944). Confirmatory factor analysis revealed one additional factor (i.e., management of psychosocial and spiritual aspects) in comparison to the original scale. Contrast tests revealed that the mean SEPC score was higher in professionals than in students (p < 0.001) and that the professionals who had higher levels of self-efficacy were older (p < 0.001), had more previous training (p < 0.001), and had more experience in end-of-life care (p = 0.001). The linear analysis results confirm a significant association between age and previous training in end-of-life care. The Spanish version of the SEPC is a reliable tool for both nursing professionals and students. The level of self-efficacy of both groups is moderate and is influenced by age, experience, and training in end-of-life care.
EEG & Eye Tracking User Experiments for Spatial Memory Task on Maps
Authors: Keskin Merve , Ooms Kristien , Dogru Ahmet , De Maeyer Philippe
Published: December 2019

The aim of this research is to evaluate the use of ET and EEG for studying the cognitive processes of expert and novice map users and to explore these processes by comparing two types of spatial memory experiments through cognitive load measurements. The first experiment consisted of single trials and participants were instructed to study a map stimulus without any time constraints in order to draw a sketch map afterwards. According to the ET metrics (i.e., average fixation duration and the number of fixations per second), no statistically significant differences emerged between experts and novices. A similar result was also obtained with EEG Frontal Alpha Asymmetry calculations. On the contrary, in terms of alpha power across all electrodes, novices exhibited significantly lower alpha power, indicating a higher cognitive load. In the second experiment, a larger number of stimuli were used to study the effect of task difficulty. The same ET metrics used in the first experiment indicated that the difference between these user groups was not statistically significant. The cognitive load was also extracted using EEG event-related spectral power changes at alpha and theta frequency bands. Preliminary data exploration mostly suggested an increase in theta power and a decrease in alpha power.
Transcriptomic Analysis of Stem Cells Treated with Moringin or Cannabidiol: Analogies and Differences in Inflammation Pathways
Authors: Chiricosta Luigi , Silvestro Serena , Pizzicannella Jacopo , Diomede Francesca , Bramanti Placido , Trubiani Oriana , Mazzon Emanuela
Published: December 2019

Inflammation is a common feature of many neurodegenerative diseases. The treatment of stem cells as a therapeutic approach to repair damage in the central nervous system represents a valid alternative. In this study, using Next-Generation Sequencing (NGS) technology, we analyzed the transcriptomic profile of human Gingival Mesenchymal Stem Cells (hGMSCs) treated with Moringin [4-(α-l-ramanosyloxy)-benzyl isothiocyanate] (hGMSCs-MOR) or with Cannabidiol (hGMSCs-CBD) at dose of 0.5 or 5 µM, respectively. Moreover, we compared their transcriptomic profiles in order to evaluate analogies and differences in pro- and anti-inflammatory pathways. The hGMSCs-MOR selectively downregulate TNF-α signaling from the beginning, reducing the expression of TNF-α receptor while hGMSCs-CBD limit its activity after the process started. The treatment with CBD downregulates the pro-inflammatory pathway mediated by the IL-1 family, including its receptor while MOR is less efficient. Furthermore, both the treatments are efficient in the IL-6 signaling. In particular, CBD reduces the effect of the pro-inflammatory JAK/STAT pathway while MOR enhances the pro-survival PI3K/AKT/mTOR. In addition, both hGMSCs-MOR and hGMSCs-CBD improve the anti-inflammatory activity enhancing the TGF-β pathway.
Whole Genome Expression Analyses of miRNAs and mRNAs Suggest the Involvement of miR-320a and miR-155-3p and their Targeted Genes in Lithium Response in Bipolar Disorder
Authors: Pisanu Claudia , Merkouri Papadima Eleni , Melis Carla , Congiu Donatella , Loizedda Annalisa , Orrù Nicola , Calza Stefano , Orrù Sandro , Carcassi Carlo , Severino Giovanni , Ardau Raffaella , Chillotti Caterina , Del Zompo Maria , Squassina Alessio
Published: December 2019

Lithium is the mainstay in the maintenance of bipolar disorder (BD) and the most efficacious pharmacological treatment in suicide prevention. Nevertheless, its use is hampered by a high interindividual variability and important side effects. Genetic and epigenetic factors have been suggested to modulate lithium response, but findings so far have not allowed identifying molecular targets with predictive value. In this study we used next generation sequencing to measure genome-wide miRNA expression in lymphoblastoid cell lines from BD patients excellent responders (ER, n = 12) and non-responders (NR, n = 12) to lithium. These data were integrated with microarray genome-wide expression data to identify pairs of miRNA/mRNA inversely and significantly correlated. Significant pairs were prioritized based on strength of association and in-silico miRNA target prediction analyses to select candidates for validation with qRT-PCR. Thirty-one miRNAs were differentially expressed in ER vs. NR and inversely correlated with 418 genes differentially expressed between the two groups. A total of 331 of these correlations were also predicted by in-silico algorithms. miR-320a and miR-155-3p, as well as three of their targeted genes (CAPNS1 (Calpain Small Subunit 1) and RGS16 (Regulator of G Protein Signaling 16) for miR-320, SP4 (Sp4 Transcription Factor) for miR-155-3p) were validated. These miRNAs and mRNAs were previously implicated in psychiatric disorders (miR-320a and SP4), key processes of the central nervous system (CAPNS1, RGS16, SP4) or pathways involved in mental illnesses (miR-155-3p). Using an integrated approach, we identified miRNAs and their targeted genes potentially involved in lithium response in BD.
Effect of Long-Term Brushing on Deflection, Maximum Load, and Wear of Stainless Steel Wires and Conventional and Spot Bonded Fiber-Reinforced Composites
Authors: Scribante Andrea , Vallittu Pekka , Lassila Lippo V. J. , Viola Annalisa , Tessera Paola , Gandini Paola , Sfondrini Maria Francesca
Published: December 2019

Fiber-reinforced composite (FRC) retainers are an aesthetic alternative to conventional Stainless Steel splints. They are generally used with a full bonded technique, but some studies demonstrated that they could be managed with a spot bonding technique to significantly decrease their rigidity. In order to propose this FRC spot bonding technique for clinical use, the aim of this study was to evaluate mechanical properties and surface wear of fibers left uncovered. Tests were made by simulating tooth brushing, comparing FRC spot bonding technique splints with stainless steel and FRC traditional technique splints. Specimens were tested both at 0.1 mm of deflection and at maximum load, showing higher values of rigidity for the FRC full bonded technique. After tooth brushing, no significant reduction in values at 0.1 mm deflection was reported, while we found a similar reduction in these values for the Stainless Steel and FRC spot bonding technique at maximum load, and no significant variation for the FRC full bonded technique. SEM images after tooth brushing showed wear for FRC fibers left uncovered, while no relevant wear signs in metal and conventional FRC fibers were noticed. Results showed that FRC spot bonding technique has advantages in mechanical properties when compared to the FRC traditional full bonding technique, also after tooth brushing. However, the surface wear after tooth brushing in the FRC spot bonding technique is considerable and other tests must be performed before promoting this technique for routine clinical use.
Decreased Activity of Blood Acid Sphingomyelinase in the Course of Multiple Myeloma
Authors: Wątek Marzena , Piktel Ewelina , Barankiewicz Joanna , Sierlecka Ewa , Kościołek-Zgódka Sylwia , Chabowska Anna , Suprewicz Łukasz , Wolak Przemysław , Durnaś Bonita , Bucki Robert , Lech-Marańda Ewa
Published: December 2019

Acid sphingomyelinase (aSMase) is involved in the generation of metabolites that function as part of the sphingolipid signaling pathway. It catalyzes the breakdown of sphingomyelin into ceramide, a bioactive lipid that, among other roles, is involved in regulation of apoptosis. Dry drop blood test (DBS) and colorimetric 2-step enzymatic assay were used to assess the activity of human blood aSMase, beta-galactosidase, and beta-glucosidase, these enzymes are lysosomal hydrolases that catalyze the degradation of related sphingolipids, of sphingolipid signaling molecules. Blood was collected from a group of healthy volunteers and patients that were diagnosed with multiple myeloma (MM) in various stages of the disease. Additionally, activity of those enzymes in patients diagnosed with other hematological cancers was also assessed. We found that aSMase activity in the blood of patients with MM (at the time of diagnosis) was 305.43 pmol/spot*20 h, and this value was significantly lower (p < 0.030) compared to the healthy group 441.88 pmol/spot*20 h. Our collected data suggest a possible role of aSMase in pathogenesis of MM development.
Endogenous Retroviruses Activity as a Molecular Signature of Neurodevelopmental Disorders
Authors: Balestrieri Emanuela , Matteucci Claudia , Cipriani Chiara , Grelli Sandro , Ricceri Laura , Calamandrei Gemma , Sinibaldi Vallebona Paola
Published: December 2019

Human endogenous retroviruses (HERVs) are genetic elements resulting from relics of ancestral infection of germline cells, now recognized as cofactors in the etiology of several complex diseases. Here we present a review of findings supporting the role of the abnormal HERVs activity in neurodevelopmental disorders. The derailment of brain development underlies numerous neuropsychiatric conditions, likely starting during prenatal life and carrying on during subsequent maturation of the brain. Autism spectrum disorders, attention deficit hyperactivity disorders, and schizophrenia are neurodevelopmental disorders that arise clinically during early childhood or adolescence, currently attributed to the interplay among genetic vulnerability, environmental risk factors, and maternal immune activation. The role of HERVs in human embryogenesis, their intrinsic responsiveness to external stimuli, and the interaction with the immune system support the involvement of HERVs in the derailed neurodevelopmental process. Although definitive proofs that HERVs are involved in neurobehavioral alterations are still lacking, both preclinical models and human studies indicate that the abnormal expression of ERVs could represent a neurodevelopmental disorders-associated biological trait in affected individuals and their parents.
The TFF Peptides xP1 and xP4 Appear in Distinctive Forms in the Xenopus laevis Gastric Mucosa: Indications for Different Protective Functions
Authors: Stürmer René , Reising Jana , Hoffmann Werner
Published: December 2019

The gastric secretory trefoil factor family (TFF) peptides xP1 and xP4 are the Xenopus laevis orthologs of mammalian TFF1 and TFF2, respectively. The aim of this study was to analyze the molecular forms of xP1 and xP4 in the X. laevis gastric mucosa by FPLC. xP1 mainly occurred in a monomeric low-molecular-mass form and only a minor subset is associated with the mucus fraction. The occurrence of monomeric xP1 is unexpected because of its odd number of cysteine residues. Probably a conserved acidic residue flanking Cys55 allows monomeric secretion. Furthermore, Cys55 is probably post-translationally modified. For the first time, we hypothesize that the free thiol of monomeric xP1-and probably also its mammalian ortholog TFF1-could have a protective scavenger function, e.g., for reactive oxygen/nitrogen species. In contrast, xP4 mainly occurs in a high-molecular-mass form and is non-covalently bound to a mucin similarly as TFF2. In vitro binding studies with radioactively labeled porcine TFF2 even showed binding to X. laevis gastric mucin. Thus, xP4 is expected to bind as a lectin to an evolutionary conserved sugar epitope of the X. laevis ortholog of mucin MUC6 creating a tight mucus barrier. Taken together, xP1 and xP4 appear to have different gastric protective functions.
Teaching an Old Molecule New Tricks: Drug Repositioning for Duchenne Muscular Dystrophy
Authors: Vitiello Libero , Tibaudo Lucia , Pegoraro Elena , Bello Luca , Canton Marcella
Published: December 2019

Duchenne muscular dystrophy (DMD) is one of the most severe forms of inherited muscular dystrophies. The disease is caused by the lack of dystrophin, a structurally essential protein; hence, a definitive cure would necessarily have to pass through some form of gene and/or cell therapy. Cell- and genetic-based therapeutics for DMD have been explored since the 1990s; recently, two of the latter have been approved for clinical use, but their efficacy is still very low. In parallel, there have been great ongoing efforts aimed at targeting the downstream pathogenic effects of dystrophin deficiency using classical pharmacological approaches, with synthetic or biological molecules. However, as it is always the case with rare diseases, R&D costs for new drugs can represent a major hurdle for researchers and patients alike. This problem can be greatly alleviated by experimenting the use of molecules that had originally been developed for different conditions, a process known as drug repurposing or drug repositioning. In this review, we will describe the state of the art of such an approach for DMD, both in the context of clinical trials and pre-clinical studies.
Pairing and Exchanging between Daypyrum villosum Chromosomes 6V#2 and 6V#4 in the Hybrids of Two Different Wheat Alien Substitution Lines
Authors: Ma Xiaolan , Xu Zhiying , Wang Jing , Chen Haiqiang , Ye Xingguo , Lin Zhishan
Published: December 2019

Normal pairing and exchanging is an important basis to evaluate the genetic relationship between homologous chromosomes in a wheat background. The pairing behavior between 6V#2 and 6V#4, two chromosomes from different Dasypyrum villosum accessions, is still not clear. In this study, two wheat alien substitution lines, 6V#2 (6A) and 6V#4 (6D), were crossed to obtain the F1 hybrids and F2 segregating populations, and the testcross populations were obtained by using the F1 as a parent crossed with wheat variety Wan7107. The chromosomal behavior at meiosis in pollen mother cells (PMCs) of the F1 hybrids was observed using a genomic in situ hybridization (GISH) technique. Exchange events of two alien chromosomes were investigated in the F2 populations using nine polymerase chain reaction (PCR) markers located on the 6V short arm. The results showed that the two alien chromosomes could pair with each other to form ring- or rod-shaped bivalent chromosomes in 79.76% of the total PMCs, and most were pulled to two poles evenly at anaphase I. Investigation of the F2 populations showed that the segregation ratios of seven markers were consistent with the theoretical values 3:1 or 1:2:1, and recombinants among markers were detected. A genetic linkage map of nine PCR markers for 6VS was accordingly constructed based on the exchange frequencies and compared with the physical maps of wheat and barley based on homologous sequences of the markers, which showed that conservation of sequence order compared to 6V was 6H and 6B > 6A > 6D. In the testcross populations with 482 plants, seven showed susceptibility to powdery mildew (PM) and lacked amplification of alien chromosomal bands. Six other plants had amplification of specific bands of both the alien chromosomes at multiple sites, which suggested that the alien chromosomes had abnormal separation behavior in about 1.5% of the PMCs in F1, which resulted in some gametes containing two alien chromosomes. In addition, three new types of chromosome substitution were developed. This study lays a foundation for alien allelism tests and further assessment of the genetic relationship among 6V#2, 6V#4, and their wheat homoeologous chromosomes.
An Ancient Mutation in the TPH1 Gene is Consistent with the Changes in Mammalian Reproductive Rhythm
Authors: Liu Chenhui , Jiang Xunping , Liu Guiqiong , Wassie Teketay , Girmay Shishay
Published: December 2019

The reproductive rhythm undergoes several changes during the evolution of mammals to adapt to local environmental changes. Although the critical roles of melatonin (MLT) in the formation of reproductive rhythm have been well established, the genetic basis for the changes of reproductive rhythm remains uncertain. Here, we constructed the phylogenetic trees of 13 melatonin synthesis, metabolism and receptor genes, estimated their divergence times, and calculated their selection pressures. Then, we evaluated the effect of positively selected and functionally related mutations on protein activity. Our results showed that there were significant positive selection sites in the three major genes, including tryptophan hydroxylase 1 (TPH1), tryptophan hydroxylase 2 (TPH2) and indoleamine-2,3-dioxygenase 1 (IDO1) that are involved in melatonin synthesis, metabolism and function. At the protein level, amino acids at the 442nd site of TPH1 protein and the 194th, 286th, 315th and 404th sites of IDO1 protein were under positive selection, and the variants of the amino acid in these sites might lead to the changes in protein function. Remarkably, the 442nd site of these positive selection sites is in the tetramerization domain of TPH1 protein, and it is proline or leucine. At this site, 89.5% of the amino acid of non-seasonal reproducing mammals was proline, while that of 88.9% of seasonal reproducing mammals was leucine. This variation of the amino acid was derived from the T/C polymorphism at the 1325th site of the TPH1 gene coding sequence, which significantly altered the TPH1 activity (p < 0.01). Interestingly, the predicted age of the allele C in the mammalian genome appeared about 126.6 million years ago, and allele T appeared about 212.6 million years ago, indicating that the evolution of the TPH1 gene was affected by the two mammalian split events and the K-T extinction event. In conclusion, the T/C polymorphism at the 1325th site in the TPH1 gene coding sequence altered TPH1 activity, suggesting that this polymorphism is consistent with the reproductive rhythm of mammals.
Contribution of Palmitic Acid to Epidermal Morphogenesis and Lipid Barrier Formation in Human Skin Equivalents
Authors: Mieremet Arnout , Helder Richard , Nadaban Andreea , Gooris Gert , Boiten Walter , El Ghalbzouri Abdoelwaheb , Bouwstra Joke A.
Published: December 2019

The outermost barrier layer of the skin is the stratum corneum (SC), which consists of corneocytes embedded in a lipid matrix. Biosynthesis of barrier lipids occurs de novo in the epidermis or is performed with externally derived lipids. Hence, in vitro developed human skin equivalents (HSEs) are developed with culture medium that is supplemented with free fatty acids (FFAs). Nevertheless, the lipid barrier formation in HSEs remains altered compared to native human skin (NHS). The aim of this study is to decipher the role of medium supplemented saturated FFA palmitic acid (PA) on morphogenesis and lipid barrier formation in HSEs. Therefore, HSEs were developed with 100% (25 μM), 10%, or 1% PA. In HSEs supplemented with reduced PA level, the early differentiation was delayed and epidermal activation was increased. Nevertheless, a similar SC lipid composition in all HSEs was detected. Additionally, the lipid organization was comparable for lamellar and lateral organization, irrespective of PA concentration. As compared to NHS, the level of monounsaturated lipids was increased and the FFA to ceramide ratio was drastically reduced in HSEs. This study describes the crucial role of PA in epidermal morphogenesis and elucidates the role of PA in lipid barrier formation of HSEs.
Effects of Variety and Grape Berry Condition of Vitis vinifera on Preference Behavior and Performance of Drosophila suzukii
Authors: Weißinger Lisa , Samuel Niklas , Breuer Michael , Müller Caroline
Published: December 2019

Drosophila suzukii is an invasive fruit pest and represents a potential economic threat to viticulture. After first observations of D. suzukii in Europe in 2008, research mainly focused on the evaluation of the host range and infestation risk for fruit and berry crops. However, the risk assessment of D. suzukii in viticulture has only recently started. Understanding the factors influencing preferences of D. suzukii for host species and varieties as well as offspring performance is essential to improve management strategies. We investigated the field infestation of different grape varieties across Baden-Wuerttemberg, southwestern Germany, between 2015 and 2018. Moreover, we performed dual-choice assays in the laboratory to investigate whether adults show preferences for certain varieties and whether offspring performance differs between varieties. Furthermore, we studied the impact of grape damage on choice behavior. Field monitoring revealed that D. suzukii show preferences for red varieties, whereas almost no oviposition occurred in white varieties. The results of dual-choice assays confirmed that D. suzukii preference and performance are influenced by grape variety and that flies preferred damaged over intact “Pinot Noir”, “Pinot Blanc”, and “Müller-Thurgau” berries. Overall, these findings may have important implications for winegrowers regarding cultivated varieties, grape health, and insecticide reduction.
Impact of Line Edge Roughness on ReRAM Uniformity and Scaling
Authors: Constantoudis Vassilios , Papavieros George , Karakolis Panagiotis , Khiat Ali , Prodromakis Themistoklis , Dimitrakis Panagiotis
Published: December 2019

We investigate the effects of Line Edge Roughness (LER) of electrode lines on the uniformity of Resistive Random Access Memory (ReRAM) device areas in cross-point architectures. To this end, a modeling approach is implemented based on the generation of 2D cross-point patterns with predefined and controlled LER and pattern parameters. The aim is to evaluate the significance of LER in the variability of device areas and their performances and to pinpoint the most critical parameters and conditions. It is found that conventional LER parameters may induce >10% area variability depending on pattern dimensions and cross edge/line correlations. Increased edge correlations in lines such as those that appeared in Double Patterning and Directed Self-assembly Lithography techniques lead to reduced area variability. Finally, a theoretical formula is derived to explain the numerical dependencies of the modeling method.
Second-Generation Implants for Load Introduction into Thin-Walled CFRP-Reinforced UHPC Beams: Implant Optimisation and Investigations of Production Technologies
Authors: Kromoser Benjamin , Gericke Oliver , Hammerl Mathias , Sobek Werner
Published: December 2019

Combining two high-performance materials—ultra-high-performance concrete (UHPC) as the matrix and carbon-fibre-reinforced composites (CFRP) as the reinforcement—opens up new possibilities for achieving very lightweight thin-walled concrete elements. This strategy, however, leads to a higher degree of material utilisation, resulting in the generation of higher forces around load introduction points and supports. The authors present a solution for increasing the performance of supports of very slender CFRP-reinforced UHPC beams by using metal implants. Implants are used in place of concrete in regions of stress concentrations and significant deviation forces. These are able to transfer high stresses and forces efficiently due to their ability to sustain both tension and compression in equal measure. A key issue in their development is the interface between the reinforced concrete and metal implant. Building on previous research, this paper deals with the conceptual design of three types of implants manufactured from different metals and with three different types of automated production technologies (water-jet cutting, metal casting with a 3D-printed plastic formwork and binder jetting of steel components). For this paper, tests were carried out to determine the load-bearing behaviour of beams with the three different types of support implants used for load introduction at the supports. A carbon rod served as bending reinforcement and a pre-formed textile reinforcement cage served as shear and constructive reinforcement.
Current State of Bone Adhesives—Necessities and Hurdles
Authors: Böker Kai O. , Richter Katharina , Jäckle Katharina , Taheri Shahed , Grunwald Ingo , Borcherding Kai , von Byern Janek , Hartwig Andreas , Wildemann Britt , Schilling Arndt F. , Lehmann Wolfgang
Published: December 2019

The vision of gluing two bone fragments with biodegradable and biocompatible adhesives remains highly fascinating and attractive to orthopedic surgeons. Possibly shorter operation times, better stabilization, lower infection rates, and unnecessary removal make this approach very appealing. After 30 years of research in this field, the first adhesive systems are now appearing in scientific reports that may fulfill the comprehensive requirements of bioadhesives for bone. For a successful introduction into clinical application, special requirements of the musculoskeletal system, challenges in the production of a bone adhesive, as well as regulatory hurdles still need to be overcome. In this article, we will give an overview of existing synthetic polymers, biomimetic, and bio-based adhesive approaches, review the regulatory hurdles they face, and discuss perspectives of how bone adhesives could be efficiently introduced into clinical application, including legal regulations.
Effects of the γ″-Ni3Nb Phase on Fatigue Behavior of Nickel-Based 718 Superalloys with Different Heat Treatments
Authors: Ling Li-Shi-Bao , Yin Zheng , Hu Zhi , Wang Jun , Sun Bao-De
Published: December 2019

The effects of the γ″-Ni3Nb phase on fatigue behavior of nickel-based 718 superalloys with standard heat treatment, hot isostatic pressing + solution treatment + aging, and hot isostatic pressing + direct aging were investigated by scanning electron microscope, transmission electron microscopy, and fatigue experiments. The standard heat treatment, hot isostatic pressing + solution treatment + aging, and hot isostatic pressing + direct aging resulted in the formation of more and smaller γ″ phases in the matrix in the nickel-based 718 superalloys. However, the grain boundaries of the hot isostatic pressing + direct aging sample showed many relatively coarse disk-like γ″ phases with major axes of ~80 nm and minor axes of ~40 nm. The hot isostatic pressing + direct aging sample with a stress amplitude of 380 MPa showed the longest high cycle fatigue life of 5.16 × 105 cycles. Laves phases and carbide inclusions were observed in the crack initiation zone, and the cracks propagated along the acicular δ phases in the nickel-based 718 superalloys. The precipitation of fine γ″ phases in the matrix and relatively coarse γ″ phases in the grain boundaries of the hot isostatic pressing + direct aging sample can hinder the movement of dislocation.
Modification of Polyacrylonitrile Fibers by Coupling to Thiosemicarbazones
Authors: Yao Yao , Liang Yonghong , Navik Rahul , Dong Xiongwei , Cai Yingjie , Zhang Ping
Published: December 2019

This work reports the modification of Polyacrylonitrile (PAN) fibers by coupling to thiosemicarbazones to achieve the biological activity for the applications in the food product packaging. After modification, seven thiosemicarbazone compounds were synthesized. The as-synthesized thiosemicarbazone compounds were bonded to PAN fibers via covalent coupling, which was confirmed using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy. The mean graft efficiency of the compounds was about 1.92%, and the antibacterial efficiency was 88.6% and 45.1% against Staphylococcus aureus (S-aureus) bacteria. All the seven thiosemicarbazone compounds exerted excellent tyrosinase activity, low cytotoxicity, excellent metal ion chelation ability, and anti-bacterial behavior against both gram-positive and negative bacteria. The mechanical properties of the fibers have been maintained without significant damage after the chemical modification. The break strength test and elongation at the break test were done to measure the fracture strength of the modified fibers. Overall, the promising properties of the modified PAN fibers show potential applications in food packaging materials for fruits and vegetables, which require long-term anti-browning effects during their transportation and storage.
Study of the Effect of Current Pulse Frequency on Ti-6Al-4V Alloy Coating Formation by Micro Arc Oxidation
Authors: Sobolev Alexander , Kossenko Alexey , Borodianskiy Konstantin
Published: December 2019

The micro arc oxidation (MAO) process has been applied to produce ceramic oxide coating on Ti-6Al-4V alloy. The MAO process was carried out at the symmetric bipolar square pulse in electrolyte containing Na2CO3 and Na2SiO3. The effect of current frequency on the surface morphology, the chemical and the phase compositions as well as the corrosion resistance was examined. Morphology and cross-sectional investigation by electron microscopy evaluated more compacted and less porous coating produced by high current frequency (1000 Hz). This alloy also exhibited a high corrosion resistance in comparison with the untreated alloy. Additionally, the alloy subjected to MAO treatment by a current frequency of 1000 Hz showed a higher corrosion resistance in comparison with alloys obtained by lower current frequencies. This behavior was attributed to more compacted and less porous morphology of the coating.
Relationship Between Matrix Cracking and Delamination in CFRP Cross-Ply Laminates Subjected to Low Velocity Impact
Authors: Tan Riming , Xu Jifeng , Sun Wei , Liu Zhun , Guan Zhidong , Guo Xia
Published: December 2019

The effect of matrix cracking on the delamination morphology inside carbon fiber reinforced plastics (CFRP) laminates during low-velocity impact (LVI) is an open question. In this paper, the relationship between matrix cracking and delamination is studied by using cross-ply laminates. Several methods, including micrograph, C-scan, and visual inspection, were adopted to characterize the damage after LVI experiments. Based on the experimental results, finite element (FE) models were established to analyze the damage mechanisms. The matrix cracking was predicted by the extended finite element method (XFEM) and the Puck criteria, while the delamination was modeled by cohesive elements. It was revealed that the matrix crack in the bottom ply not only promoted the outward propagation of delamination but also contributed to the narrow delamination beneath the impact location. Multiple matrix cracks occurred in the middle ply. The ones close to the plate center initiated the delamination and prevented large-scale delamination beneath the impact location. For the cracks that were far away, no significant effect on delamination was found. In conclusion, the stress redistribution caused by the crack opening determines the delamination.
Efficient Pipelined Broadcast with Monitoring Processing Node Status on a Multi-Core Processor
Authors: Park Jongsu
Published: December 2019

This paper presents an efficient pipelined broadcasting algorithm with the inter-node transmission order change technique considering the communication status of processing nodes. The proposed method changes the transmission order for the broadcast operation based on the communication status of processing nodes. When a broadcast operation is received, a local bus checks the remaining pre-existing transmission data size of each processing node; it then transmits data according to the changed transmission order using the status information. Therefore, the synchronization time can be hidden for the remaining time, until the pre-existing data transmissions finish; as a result, the overall broadcast completion time is reduced. The simulation results indicated that the speed-up ratio of the proposed algorithm was up to 1.423, compared to that of the previous algorithm. To demonstrate physical implementation feasibility, the message passing engine (MPE) with the proposed broadcast algorithm was designed by using Verilog-HDL, which supports four processing nodes. The logic synthesis results with TSMC 0.18 μm process cell libraries show that the logic area of the proposed MPE is 2288.1 equivalent NAND gates, which is approximately 2.1% of the entire chip area. Therefore, performance improvement in multi-core processors is expected with a small hardware area overhead.
Valorization of Aquaculture By-Products of Salmonids to Produce Enzymatic Hydrolysates: Process Optimization, Chemical Characterization and Evaluation of Bioactives
Authors: Vázquez José Antonio , Sotelo Carmen G. , Sanz Noelia , Pérez-Martín Ricardo I. , Rodríguez-Amado Isabel , Valcarcel Jesus
Published: December 2019

In the present manuscript, various by-products (heads, trimmings, and frames) generated from salmonids (rainbow trout and salmon) processing were evaluated as substrates for the production of fish protein hydrolysates (FPHs), potentially adequate as protein ingredients of aquaculture feeds. Initially, enzymatic conditions of hydrolysis were optimized using second order rotatable designs and multivariable statistical analysis. The optimal conditions for the Alcalase hydrolysis of heads were 0.1% (v/w) of enzyme concentration, pH 8.27, 56.2°C, ratio (Solid:Liquid = 1:1), 3 h of hydrolysis, and agitation of 200 rpm for rainbow trout and 0.2% (v/w) of enzyme, pH 8.98, 64.2 °C, 200 rpm, 3 h of hydrolysis, and S:L = 1:1 for salmon. These conditions obtained at 100 mL-reactor scale were then validated at 5L-reactor scale. The hydrolytic capacity of Alcalase and the protein quality of FPHs were excellent in terms of digestion of wastes (Vdig > 84%), high degrees of hydrolysis (Hm > 30%), high concentration of soluble protein (Prs > 48 g/L), good balance of amino acids, and almost full in vitro digestibility (Dig > 93%). Fish oils were recovered from wastes jointly with FPHs and bioactive properties of hydrolysates (antioxidant and antihypertensive) were also determined. The salmon FPHs from trimmings + frames (TF) showed the higher protein content in comparison to the rest of FPHs from salmonids. Average molecular weights of salmonid-FPHs ranged from 1.4 to 2.0 kDa and the peptide sizes distribution indicated that hydrolysates of rainbow trout heads and salmon TF led to the highest percentages of small peptides (0–500 Da).
Integrated Multitrophic Aquaculture By-Products with Added Value: The Polychaete Sabella spallanzanii and the Seaweed Chaetomorpha linum as Potential Dietary Ingredients
Authors: Stabili Loredana , Cecere Ester , Licciano Margherita , Petrocelli Antonella , Sicuro Benedetto , Giangrande Adriana
Published: December 2019

Aquaculture expansion is limited by the negative environmental impact of the waste and the need for alternative sources in the diet of reared fish. In this framework, for the first time, the survival rates, biomass gain, and fatty acid profiles of the polychaete Sabella spallanzanii and the macroalga Chaetomorpha linum, reared/cultivated as bioremediators in an integrated multitrophic aquaculture system (IMTA), were evaluated for their potential reuse applications. Results showed that these organisms represent a natural source of omega-3 and omega-6. On account of the overall results and the high biomass obtained as by-products, a preliminary study was performed employing both S. spallanzanii and C. linum as new dietary ingredients to feed different sized Dicentrarchus labrax. Fish survival rate, biomass growth, and specific growth rate were determined resulting in no significant differences between control and treated fishes. Histological analyses showed no alterations of the stomach tunica mucosa and submucosa in treated fishes. The eco-friendly approaches applied in the here-realized IMTA system could guarantee the achievement of sustainable by-products represented by the bioremediators S. spallanzanii and C. linum, as well as their reliability as a natural source of compounds beneficial to fish and human health.
Exploiting the Feedstock Flexibility of the Emergent Synthetic Biology Chassis Vibrio natriegens for Engineered Natural Product Production
Authors: Ellis Gregory A. , Tschirhart Tanya , Spangler Joseph , Walper Scott A. , Medintz Igor L. , Vora Gary J.
Published: December 2019

A recent goal of synthetic biology has been to identify new chassis that provide benefits lacking in model organisms. Vibrio natriegens is a marine Gram-negative bacterium which is an emergent synthetic biology chassis with inherent benefits: An extremely fast growth rate, genetic tractability, and the ability to grow on a variety of carbon sources (“feedstock flexibility”). Given these inherent benefits, we sought to determine its potential to heterologously produce natural products, and chose beta-carotene and violacein as test cases. For beta-carotene production, we expressed the beta-carotene biosynthetic pathway from the sister marine bacterium Vibrio campbellii, as well as the mevalonate biosynthetic pathway from the Gram-positive bacterium Lactobacillus acidophilus to improve precursor abundance. Violacein was produced by expressing a biosynthetic gene cluster derived from Chromobacterium violaceum. Not only was V. natriegens able to heterologously produce these compounds in rich media, illustrating its promise as a new chassis for small molecule drug production, but it also did so in minimal media using a variety of feedstocks. The ability for V. natriegens to produce natural products with multiple industrially-relevant feedstocks argues for continued investigations into the production of more complex natural products in this chassis.