bluuebunny/crossref_metadata_2025 huggingface dataset:
Network-Based Integrative Analysis of Genomics, Epigenomics and Transcriptomics in Autism Spectrum Disorders
Authors: Di Nanni Noemi , Bersanelli Matteo , Cupaioli Francesca Anna , Milanesi Luciano , Mezzelani Alessandra , Mosca Ettore
Published: July 2019

Current studies suggest that autism spectrum disorders (ASDs) may be caused by many genetic factors. In fact, collectively considering multiple studies aimed at characterizing the basic pathophysiology of ASDs, a large number of genes has been proposed. Addressing the problem of molecular data interpretation using gene networks helps to explain genetic heterogeneity in terms of shared pathways. Besides, the integrative analysis of multiple omics has emerged as an approach to provide a more comprehensive view of a disease. In this work, we carry out a network-based meta-analysis of the genes reported as associated with ASDs by studies that involved genomics, epigenomics, and transcriptomics. Collectively, our analysis provides a prioritization of the large number of genes proposed to be associated with ASDs, based on genes’ relevance within the intracellular circuits, the strength of the supporting evidence of association with ASDs, and the number of different molecular alterations affecting genes. We discuss the presence of the prioritized genes in the SFARI (Simons Foundation Autism Research Initiative) database and in gene networks associated with ASDs by other investigations. Lastly, we provide the full results of our analyses to encourage further studies on common targets amenable to therapy.
Blockade of STAT3 Signaling Contributes to Anticancer Effect of 5-Acetyloxy-6,7,8,4′-Tetra-Methoxyflavone, a Tangeretin Derivative, on Human Glioblastoma Multiforme Cells
Authors: Cheng Yen-Po , Li Shiming , Chuang Wan-Ling , Li Chia-Hsuan , Chen Guan-Jun , Chang Ching-Chin , Or Chi-Hung R. , Lin Ping-Yi , Chang Chia-Che
Published: July 2019

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with poor prognosis, largely due to resistance to current radiotherapy and Temozolomide chemotherapy. The constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) is evidenced as a pivotal driver of GBM pathogenesis and therapy resistance, and hence, is a promising GBM drug target. 5-acetyloxy-6,7,8,4′-tetramethoxyflavone (5-AcTMF) is an acetylated derivative of Tangeretin which is known to exert anticancer effects on breast, colon, lung, and multiple myeloma; however, its effect on GBM remains elusive. Herein, we reported that 5-AcTMF suppressed the viability and clonogenicity along with inducing apoptosis in multiple human GBM cell lines. Mechanistic analyses further revealed that 5-AcTMF lowered the levels of Tyrosine 705-phosphorylated STAT3 (p-STAT3), a canonical marker of STAT3 activation, but also dampened p-STAT3 upregulation elicited by Interleukin-6. Notably, ectopic expression of dominant-active STAT3 impeded 5-AcTMF-induced suppression of viability and clonogenicity plus apoptosis induction in GBM cells, confirming the prerequisite of STAT3 blockage for the inhibitory action of 5-AcTMF on GBM cell survival and growth. Additionally, 5-AcTMF impaired the activation of STAT3 upstream kinase JAK2 but also downregulated antiapoptotic BCL-2 and BCL-xL in a STAT3-dependent manner. Moreover, the overexpression of either BCL-2 or BCL-xL abrogated 5-AcTMF-mediated viability reduction and apoptosis induction in GBM cells. Collectively, we, for the first time, revealed the anticancer effect of 5-AcTMF on GBM cells, which was executed via thwarting the JAK2-STAT3-BCL-2/BCL-xL signaling axis. Our findings further implicate the therapeutic potential of 5-AcTMF for GBM treatment.
Synthesis of Graphene Oxide-Fe3O4 Based Nanocomposites Using the Mechanochemical Method and in Vitro Magnetic Hyperthermia
Authors: Narayanaswamy Venkatesha , Obaidat Ihab M. , Kamzin Aleksandr S. , Latiyan Sachin , Jain Shilpee , Kumar Hemant , Srivastava Chandan , Alaabed Sulaiman , Issa Bashar
Published: July 2019

The study presented in this work consists of two parts: The first part is the synthesis of Graphene oxide-Fe3O4 nanocomposites by a mechanochemical method which, is a mechanical process that is likely to yield extremely heterogeneous particles. The second part includes a study on the efficacy of these Graphene oxide-Fe3O4 nanocomposites to kill cancerous cells. Iron powder, ball milled along with graphene oxide in a toluene medium, underwent a controlled oxidation process. Different phases of GO-Fe3O4 nanocomposites were obtained based on the composition used for milling. As synthesized nanocomposites were characterized by x-ray diffraction (XRD), alternating magnetic field (AFM), Raman spectroscopy, and a vibrating sample magnetometer (VSM). Additionally, the magnetic properties required to obtain high SAR values (Specific Absorption Rate-Power absorbed per unit mass of the magnetic nanocomposite in the presence of an applied magnetic field) for the composite were optimized by varying the milling time. Nanocomposites milled for different extents of time have shown differential behavior for magneto thermic heating. The magnetic composites synthesized by the ball milled method were able to retain the functional groups of graphene oxide. The efficacy of the magnetic nanocomposites for killing of cancerous cells is studied in vitro using HeLa cells in the presence of an AC (Alternating Current) magnetic field. The morphology of the HeLa cells subjected to 10 min of AC magnetic field changed considerably, indicating the death of the cells.
Role of B-Cell Translocation Gene 1 in the Pathogenesis of Endometriosis
Authors: Kim Jeong Sook , Choi Young Sik , Park Ji Hyun , Yun Jisun , Kim Soohyun , Lee Jae Hoon , Yun Bo Hyon , Park Joo Hyun , Seo Seok Kyo , Cho SiHyun , Kim Hyun-Soo , Lee Byung Seok
Published: July 2019

Estrogen affects endometrial cellular proliferation by regulating the expression of the c-myc gene. B-cell translocation gene 1 (BTG1), a translocation partner of the c-myc, is a tumor suppressor gene that promotes apoptosis and negatively regulates cellular proliferation and cell-to-cell adhesion. The aim of this study was to determine the role of BTG1 in the pathogenesis of endometriosis. BTG1 mRNA and protein expression was evaluated in eutopic and ectopic endometrium of 30 patients with endometriosis (endometriosis group), and in eutopic endometrium of 22 patients without endometriosis (control group). The effect of BTG1 downregulation on cellular migration, proliferation, and apoptosis was evaluated using transfection of primarily cultured human endometrial stromal cells (HESCs) with BTG1 siRNA. BTG1 mRNA expression level of eutopic and ectopic endometrium of endometriosis group were significantly lower than that of the eutopic endometrium of the control group. Migration and wound healing assays revealed that BTG1 downregulation resulted in a significant increase in migration potential of HESCs, characterized by increased expression of matrix metalloproteinase 2 (MMP2) and MMP9. Downregulation of BTG1 in HESCs significantly reduced Caspase 3 expression, indicating a decrease in apoptotic potential. In conclusion, our data suggest that downregulation of BTG1 plays an important role in the pathogenesis of endometriosis.
Interleukin-10 Facilitates Glutamatergic Synaptic Transmission and Homeostatic Plasticity in Cultured Hippocampal Neurons
Authors: Nenov Miroslav N. , Konakov Maxim V. , Teplov Ilia Y. , Levin Sergey G.
Published: July 2019

Anti-inflammatory cytokines are known to exert neuroprotective action ameliorating aberrant neuronal network activity associated with inflammatory responses. Yet, it is still not fully understood if anti-inflammatory cytokines play a significant role in the regulation of synaptic activity under normal conditions. Thus, the aim of our study was to investigate the effect of Interleukin-10 (IL-10) on neuronal synaptic transmission and plasticity. For this we tested the effect of IL-10 on miniature excitatory postsynaptic currents (mEPSC) and intracellular Ca2+ responses using whole-cell patch clamp and fluorescence microscopy in 13–15 DIV primary hippocampal neuroglial culture. We found that IL-10 significantly potentiated basal glutamatergic excitatory synaptic transmission within 15 min after application. Obtained results revealed a presynaptic nature of the effect, as IL-10 in a dose-dependent manner significantly increased the frequency but not the amplitude of mEPSC. Further, we tested the effect of IL-10 on mEPSC in a model of homeostatic synaptic plasticity (HSP) induced by treatment of primary hippocampal culture with 1 µM of tetrodotoxin (TTX) for a 24 h. It was found that 15 min application of IL-10 at established HSP resulted in enhanced mEPSC frequency, thus partially compensating for a decrease in the mEPSC frequency associated with TTX-induced HSP. Next, we studied if IL-10 can influence induction of HSP. We found that co-incubation of IL-10 with 1 µM of TTX for 24 h induced synaptic scaling, significantly increasing the amplitude of mEPSC and Ca2+ responses to application of the AMPA agonist, 5-Fluorowillardiine, thus facilitating a compensatory postsynaptic mechanism at HSP condition. Our results indicate that IL-10 potentiates synaptic activity in a dose- and time-dependent manner exerting both presynaptic (short-term exposure) and postsynaptic (long-term exposure) action. Obtained results demonstrate involvement of IL-10 in the regulation of basal glutamatergic synaptic transmission and plasticity at normal conditions.
Visualization of Bacterial Protein Complexes Labeled with Fluorescent Proteins and Nanobody Binders for STED Microscopy
Authors: Cramer Kimberly , Bolender Anna-Lena , Stockmar Iris , Jungmann Ralf , Kasper Robert , Shin Jae Yen
Published: July 2019

In situ visualization of molecular assemblies near their macromolecular scale is a powerful tool to investigate fundamental cellular processes. Super-resolution light microscopies (SRM) overcome the diffraction limit and allow researchers to investigate molecular arrangements at the nanoscale. However, in bacterial cells, visualization of these assemblies can be challenging because of their small size and the presence of the cell wall. Thus, although conceptually promising, successful application of SRM techniques requires careful optimization in labeling biochemistry, fluorescent dye choice, bacterial biology and microscopy to gain biological insights. Here, we apply Stimulated Emission Depletion (STED) microscopy to visualize cell division proteins in bacterial cells, specifically E. coli and B. subtilis. We applied nanobodies that specifically recognize fluorescent proteins, such as GFP, mCherry2 and PAmCherry, fused to targets for STED imaging and evaluated the effect of various organic fluorescent dyes on the performance of STED in bacterial cells. We expect this research to guide scientists for in situ macromolecular visualization using STED in bacterial systems.
“Biological Adhesion” is a Significantly Regulated Molecular Process during Long-Term Primary In Vitro Culture of Oviductal Epithelial Cells (Oecs): A Transcriptomic and Proteomic Study
Authors: Budna-Tukan Joanna , Światły-Błaszkiewicz Agata , Celichowski Piotr , Kałużna Sandra , Konwerska Aneta , Sujka-Kordowska Patrycja , Jankowski Maurycy , Kulus Magdalena , Jeseta Michal , Piotrowska-Kempisty Hanna , Józkowiak Małgorzata , Antosik Paweł , Bukowska Dorota , Skowroński Mariusz T. , Matysiak Jan , Nowicki Michał , Kempisty Bartosz
Published: July 2019

Oviductal epithelial cells (OECs) actively produce stimulating and protecting factors, favoring survival and viability of gametes and early embryos. The oviduct participates in the initial reproductive events, which strongly depends on adhesion. The analysis of differential gene expression in OECs, during long-term in vitro culture, enables recognition of new molecular markers regulating several processes, including “biological adhesion”. Porcine oviducts were stained with hematoxylin and eosin, as well as with antibodies against epithelial markers. Then, OECs were long-term in vitro cultured and after 24 h, 7, 15, and 30 days of culture were subjected to transcriptomic and proteomic assays. Microarrays were employed to evaluate gene expression, with Matrix-assisted laser desorption/ionization-time of light (MALDI-TOF) mass spectrometry applied to determine the proteome. The results revealed proper morphology of the oviducts and typical epithelial structure of OECs during the culture. From the set of differentially expressed genes (DEGs), we have selected the 130 that encoded proteins detected by MALDI-TOF MS analysis. From this gene pool, 18 significantly enriched gene ontology biological processes (GO BP) terms were extracted. Among them we focused on genes belonging to “biological adhesion” GO BP. It is suggested that increased expression of studied genes can be attributed to the process of intensive secretion of substances that exhibit favorable influence on oviductal environment, which prime gametes adhesion and viability, fertilization, and early embryo journey.
Comprehensive Analysis of Soybean Mosaic Virus P3 Protein Interactors and Hypersensitive Response-Like Lesion-Inducing Protein Function
Authors: Luan Hexiang , Liao Wenlin , Niu Haopeng , Cui Xiaoyan , Chen Xin , Zhi Haijian
Published: July 2019

Soybean mosaic virus (SMV) is one of the most prevalent and important pathogens of soybean, which produces 11 proteins, and the third protein, P3, was suggested to be involved in virus movement and replication, as well as host infection. During the virus infection, host proteins are essential in the virus cycle. However, there is no comprehensive report on the network of host proteins that interact with P3. Fifty-one interactors were identified by using the P3 protein as the bait against the SMV SC15 strain-challenged soybean cDNA library. These proteins were classified into five groups, including transport and protein transport-related proteins, defense and disease-related proteins, photosynthesis proteins, cellular metabolic proteins, and unknown proteins. Among these proteins, the protein defined as hypersensitive response-like lesion-inducing (HRLI) appeared multiple times and showed strong affinity with P3, which indicated its important role in SMV infection. Thus, it was chosen for further investigation. Phylogenetic classification showed that paralog proteins GmHRLI-1 and GmHRLI-2 clustered together and shared 90% homologous identity. Bimolecular fluorescence complementation (BiFC) assay was carried out to confirm the interaction, and fluorescence was detected at the cell periplasmic as well as at the nucleus. Subcellular localization showed that GmHRLI was localized to the cell periplasmic, while the co-localization of GmHRLI and P3 signals was also observed in the nucleus, suggesting that GmHRLI could interact with P3 and promoted the translation of P3 to the nucleus. Moreover, the gene expression of GmHRLI was abundant in the roots, leaves, and flowers, and could be induced by SMV infection, suggesting its involvement in SMV infection. Our results together lay the foundation to explore the mechanisms of P3 in the HR process and the HRLI protein function in SMV response.
Chemi-Net: A Molecular Graph Convolutional Network for Accurate Drug Property Prediction
Authors: Liu Ke , Sun Xiangyan , Jia Lei , Ma Jun , Xing Haoming , Wu Junqiu , Gao Hua , Sun Yax , Boulnois Florian , Fan Jie
Published: July 2019

Absorption, distribution, metabolism, and excretion (ADME) studies are critical for drug discovery. Conventionally, these tasks, together with other chemical property predictions, rely on domain-specific feature descriptors, or fingerprints. Following the recent success of neural networks, we developed Chemi-Net, a completely data-driven, domain knowledge-free, deep learning method for ADME property prediction. To compare the relative performance of Chemi-Net with Cubist, one of the popular machine learning programs used by Amgen, a large-scale ADME property prediction study was performed on-site at Amgen. For all 13 data sets, Chemi-Net resulted in higher R2 values compared with the Cubist benchmark. The median R2 increase rate over Cubist was 26.7%. We expect that the significantly increased accuracy of ADME prediction seen with Chemi-Net over Cubist will greatly accelerate drug discovery.
Non-Linear Relationship between Anti-Apolipoprotein A-1 IgGs and Cardiovascular Outcomes in Patients with Acute Coronary Syndromes
Authors: Vuilleumier Nicolas , Pagano Sabrina , Combescure Christophe , Gencer Baris , Virzi Julien , Räber Lorenz , Carballo David , Carballo Sebastian , Nanchen David , Rodondi Nicolas , Windecker Stephan , Hazen Stanley L. , Wang Zeneng , Li Xinmin S. , von Eckardstein Arnold , Matter Christian M. , Lüscher Thomas F. , Klingenberg Roland , Mach Francois
Published: July 2019

Autoantibodies against apolipoprotein A-I (anti-apoA-I IgGs) are prevalent in atherosclerosis-related conditions. It remains elusive whether they improve the prognostic accuracy of the Global Registry of Acute Coronary Events (GRACE) score 2.0 (GS) in acute coronary syndromes (ACS). In this prospective multicenter registry, 1713 ACS patients were included and followed for 1 year. The primary endpoint (major adverse cardiovascular events (MACE)) was defined as the composite of myocardial infarction, stroke (including transient ischemic attack), or cardiovascular (CV) death with individual events independently adjudicated. Plasma levels of anti-apoA-I IgGs upon study inclusion were assessed using ELISA. The association between anti-apoA-I IgGs and incident MACE was assessed using Cox models with splines and C-statistics. One-year MACE incidence was 8.4% (144/1713). Anti-apoA-I IgG levels were associated with MACE with a non-linear relationship (p = 0.01), which remained unchanged after adjusting for the GS (p = 0.04). The hazard increased progressively across the two first anti-apoA-I IgG quartiles before decreasing thereafter. Anti-apoA-I IgGs marginally improved the prognostic accuracy of the GS (c-statistics increased from 0.68 to 0.70). In this multicenter study, anti-apoA-I IgGs were predictive of incident MACE in ACS independently of the GS but in a nonlinear manner. The practical implications of these findings remain to be defined.
Economic Challenges in Nutritional Management
Authors: Reber Emilie , Norman Kristina , Endrich Olga , Schuetz Philipp , Frei Andreas , Stanga Zeno
Published: July 2019

Disease-related malnutrition (DRM) is a highly prevalent independent risk and cost factor with significant influence on mortality, morbidity, length of hospital stay (LOS), functional impairment and quality of life. The aim of our research was to estimate the economic impact of the introduction of routinely performed nutritional screening (NS) in a tertiary hospital, with subsequent nutritional interventions (NI) in patients with potential or manifest DRM. Economic impact analysis of natural detection of inpatients at risk and estimation of the change in economic activity after the implementation of a systematic NS were performed. The reference population for natural detection of DRM is about 20,000 inpatients per year. Based on current data, DRM prevalence is estimated at 20%, so 4000 patients with potential and manifest DRM should be detected. The NI costs were estimated at CHF 0.693 million, with savings of CHF 1.582 million (LOS reduction) and CHF 0.806 million in additional revenue (SwissDRG system). Thus, the introduction of routine NS generates additional costs of CHF 1.181 million that are compensated by additional savings of CHF 2.043 million and an excess in additional revenue of CHF 2.071 million. NS with subsequent adequate nutritional intervention shows an economic potential for hospitals.
Comparison of Bipolar Plasma Vaporization versus Standard Holmium Laser Enucleation of the Prostate: Surgical Procedures and Clinical Outcomes for Small Prostate Volumes
Authors: Kim Kang Sup , Lee Sung Hyun , Cho Hyuk Jin , Suh Hong Jin , Lee Dong Hwan , Choi Yong Sun
Published: July 2019

Bipolar plasma vaporization of the prostate (BPVP) is an attractive alternative to resection. There are numerous studies comparing transurethral resection of prostate or photoselective vaporization of the prostate with BPVP; however, there is a lack of data comparing holmium laser enucleation of the prostate (HoLEP) with BPVP. We aimed to compare HoLEP and BPVP with a focus on functional outcomes, safety, and complications. Methods: From January 2017 to June 2018, patients who underwent HoLEP or BPVP for benign prostatic hypertrophy were enrolled in this study. Inclusion criteria were a prostate volume <40 mL measured by transrectal ultrasound, international prostate symptom score (IPSS) >7, maximum urinary flow rate (Qmax) <15 mL/s, and postvoiding residual volume (PVR) >100 mL. Perioperative and postoperative parameters including IPSS, Qmax, quality of life, PVR, and complications were compared between groups. Results: Sixty-three patients were enrolled in this study. There were small differences in perioperative parameters. Hospital stays and catheterization periods were significantly shorter in the BPVP group. The postoperative complications were comparable between groups. PVR was comparable in both groups except for 1 month postoperatively. The incontinence rate was higher in the HoLEP group, but without statistical significance. Conclusion: In terms of surgical safety and efficacy as well as patient comfort, BPVP is comparable with HoLEP for small prostate volumes. BPVP can be a viable alternative technique in small BPH surgical treatment.
Associations of Plasma 3-Methylhistidine with Frailty Status in French Cohorts of the FRAILOMIC Initiative
Authors: Kochlik Bastian , Stuetz Wolfgang , Pérès Karine , Féart Catherine , Tegner Jesper , Rodriguez-Mañas Leocadio , Grune Tilman , Weber Daniela
Published: July 2019

Frailty and sarcopenia are characterized by a loss of muscle mass and functionality and are diagnosed mainly by functional tests and imaging parameters. However, more muscle specific biomarkers are needed to improve frailty diagnosis. Plasma 3-methylhistidine (3-MH), as well as the 3-MH-to-creatinine (3-MH/Crea) and 3-MH-to-estimated glomerular filtration rate (3-MH/eGFR) ratios might support the diagnosis of frailty. Therefore, we investigated the cross-sectional associations between plasma 3-MH, 3-MH/Crea and 3-MH/eGFR with the frailty status of community-dwelling individuals (>65 years). 360 participants from two French cohorts of the FRAILOMIC initiative were classified into robust, pre-frail and frail according to Fried’s frailty criteria. General linear models as well as bivariate and multiple linear and logistic regression models, which were adjusted for several confounders, were applied to determine associations between biomarkers and frailty status. The present study consisted of 37.8% robust, 43.1% pre-frail and 19.2% frail participants. Frail participants had significantly higher plasma 3-MH, 3-MH/Crea and 3-MH/eGFR ratios than robust individuals, and these biomarkers were positively associated with frailty status. Additionally, the likelihood to be frail was significantly higher for every increase in 3-MH (1.31-fold) and 3-MH/GFR (1.35-fold) quintile after adjusting for confounders. We conclude that 3-MH, 3-MH/Crea and 3-MH/eGFR in plasma might be potential biomarkers to identify frail individuals or those at higher risk to be frail, and we assume that there might be biomarker thresholds to identify these individuals. However, further, especially longitudinal studies are needed.
The Role of Hedgehog Signaling in Adult Lung Regeneration and Maintenance
Authors: Wang Chaoqun , Cassandras Monica , Peng Tien
Published: July 2019

As a secreted morphogen, Sonic Hedgehog (SHH) determines differential cell fates, behaviors, and functions by forming a gradient of Hedgehog (Hh) activation along an axis of Hh-receptive cells during development. Despite clearly delineated roles for Hh during organ morphogenesis, whether Hh continues to regulate cell fate and behavior in the same fashion in adult organs is less understood. Adult organs, particularly barrier organs interfacing with the ambient environment, are exposed to insults that require renewal of cellular populations to maintain structural integrity. Understanding key aspects of Hh’s ability to generate an organ could translate into conceptual understanding of Hh’s ability to maintain organ homeostasis and stimulate regeneration. In this review, we will summarize the current knowledge about Hh signaling in regulating adult lung regeneration and maintenance, and discuss how alteration of Hh signaling contributes to adult lung diseases.
Mene Mene Tekel Upharsin: Clerical Speed and Elementary Cognitive Speed are Different by Virtue of Test Mode Only
Authors: Schmitz Florian , Wilhelm Oliver
Published: July 2019

Current taxonomies of intelligence comprise two factors of mental speed, clerical speed (Gs), and elementary cognitive speed (Gt). Both originated from different research traditions and are conceptualized as dissociable constructs in current taxonomies. However, previous research suggests that tasks of one category can be transferred into the other category by simply changing the mode of administration, i.e., in form of a paper-and-pencil test or in from of a computer-based elementary cognitive task. However, cross-mode correlations for specific tasks are usually only moderate. In the present study, mental speed was assessed as a broad construct across different tasks and stimulus materials. This allowed modeling mental speed as a hierarchical construct for paper-and-pencil as well as for computer-based tests. Cross-mode correlations of the respective general factors were moderate (r = 0.64), while the cross-mode correlations of task-specific components depended on task type (r = 0.12 to r = 0.71). Only the g factors of mental speed, but not the task-specific components, were found to be related with working memory capacity as a marker of cognitive ability. The speed general factor modeled across computer-based tests was more highly correlated with working memory capacity (r = 0.66) than the general factor modeled across paper-and-pencil tests (r = 0.46). These findings corroborate a crucial role of the assessment method and imply that validity of speed tests is affected by the choice of the test format.
Legitimacy Dilemmas in Direct Government Intervention: The Case of Public Land Development, an Example from the Netherlands
Authors: Woestenburg Alexander , van der Krabben Erwin , Spit Tejo
Published: July 2019

The current paper examines the legitimacy dilemmas that rise from local governments’ direct policy instruments and market interventions. It takes the case of public land management strategies. The paper argues that current societal challenges—such as energy transition, climate change and inclusive urban innovation—require planning practices to be more effective. Direct government instruments such as direct market interventions have proven to significantly reduce the implementation gap of planning practice. Looking at significant urban challenges, municipalities worldwide could be urged to apply such direct government instruments on a larger scale in the future. However, although direct government intervention in markets can be very effective, it is also controversial in terms of legitimacy. It explicitly and inevitably introduces financial incentives to the organization of government. Balancing these incentives against spatial planning interests unavoidably causes dilemmas. Based on eight Dutch case studies, this paper develops a framework to systematically spell out the legitimacy dilemmas that stem from public market intervention. It facilitates an explicit discussion on varying instrumental rationalities and improving the legitimacy of public action.
Synthetic Approaches for Nucleic Acid Delivery: Choosing the Right Carriers
Authors: Ni Rong , Feng Ruilu , Chau Ying
Published: July 2019

The discovery of the genetic roots of various human diseases has motivated the exploration of different exogenous nucleic acids as therapeutic agents to treat these genetic disorders (inherited or acquired). However, the physicochemical properties of nucleic acids render them liable to degradation and also restrict their cellular entrance and gene translation/inhibition at the correct cellular location. Therefore, gene condensation/protection and guided intracellular trafficking are necessary for exogenous nucleic acids to function inside cells. Diversified cationic formulation materials, including natural and synthetic lipids, polymers, and proteins/peptides, have been developed to facilitate the intracellular transportation of exogenous nucleic acids. The chemical properties of different formulation materials determine their special features for nucleic acid delivery, so understanding the property–function correlation of the formulation materials will inspire the development of next-generation gene delivery carriers. Therefore, in this review, we focus on the chemical properties of different types of formulation materials and discuss how these formulation materials function as protectors and cellular pathfinders for nucleic acids, bringing them to their destination by overcoming different cellular barriers.
Influence of BOF and GGBFS Based Alkali Activated Materials on the Properties of Porous Concrete
Authors: Kuo Wen-Ten , Gao Yi-Syuan , Juang Chuen-Ul
Published: July 2019

In this study, environmentally friendly ground granulated blast furnace slag (GGBFS) based alkali activated materials and basic oxygen furnace slags (BOFs) were used as bonding materials and aggregates, respectively, to produce novel, environmentally friendly GGBFS based porous concrete. Porous concrete with a particle size of 4.75–9.5 mm and 9.5–19.00 mm was used as an aggregate. The “liquid-to-solid ratios” (L/S) variable was set at set at 0.5 and 0.6, and the “percentage of pore filling paste ratio” variable was controlled at 40%, 50%, and 60%. The curing period was set at 28 d, and the relationship between connected porosity and permeability, as well as that between unit weight and the pore filling paste ratio percentage were explored using analysis of variance. The results showed that the porous concrete had a maximum compressive strength of 8.31 MPa. The following results were obtained. An increase in percentage of pore filling paste ratio increased compressive strength. Permeability was measured at 4.67 cm/s and was positively correlated with porosity. An increase in porosity increased permeability, in which porosity was positively correlated with the percentage of pore filling paste ratio. The maximum splitting strength achieved during the 28 d was 1.46 MPa, showing a trend similar to that of compressive strength.
Sustainable Utilization of Metals-Processing, Recovery and Recycling
Authors: Friedrich Bernd
Published: July 2019

Our modern everyday life and thus our technical progress is based on a variety of metals [...]
Optimization of Process Parameters to Improve the Effective Area of Deposition in GMAW-Based Additive Manufacturing and its Mechanical and Microstructural Analysis
Authors: Waqas Ali , Qin Xiansheng , Xiong Jiangtao , Wang Hongbo , Zheng Chen
Published: July 2019

Additive manufacturing of metals using gas metal arc welding has an associated problem of variations of height in the onset and extinguishing parts of the weld bead. In this research, robot-assisted welding has been performed to investigate the problem, using AWS ER70S-6 low alloy steel welding electrode wire. After adjustment of welding parameters for a single-layer, single-pass, an optimal profile of welding energy was used to construct a thin wall which exhibited good forming characteristics with an effective area of approximately 97%. The resulting structure was ductile in nature with better tensile strength and microhardness as compared to the rolled steel available in industry with similar carbon content. The microstructure analysis revealed equiaxed grains in most parts of the structure having a fine grain size.
Preparation of Chitosan–Hexaconazole Nanoparticles as Fungicide Nanodelivery System for Combating Ganoderma Disease in Oil Palm
Authors: Maluin Farhatun Najat , Hussein Mohd Zobir , Yusof Nor Azah , Fakurazi Sharida , Idris Abu Seman , Zainol Hilmi Nur Hailini , Jeffery Daim Leona Daniela
Published: July 2019

Fungicide is used to control fungal disease by destroying and inhibiting the fungus or fungal spores that cause the disease. However, failure to deliver fungicide to the disease region leads to ineffectiveness in the disease control. Hence, in the present study, nanotechnology has enabled the fungicide active agents (hexaconazole) to be encapsulated into chitosan nanoparticles with the aim of developing a fungicide nanodelivery system that can transport them more effectively to the target cells (Ganoderma fungus). A pathogenic fungus, Ganoderma boninense (G. boninense), is destructive to oil palm whereby it can cause significant loss to oil palm plantations located in the Southeast Asian countries, especially Malaysia and Indonesia. In regard to this matter, a series of chitosan nanoparticles loaded with the fungicide, hexaconazole, was prepared using various concentrations of crosslinking agent sodium tripolyphosphate (TPP). The resulting particle size revealed that the increase of the TPP concentration produced smaller particles. In addition, the in vitro fungicide released at pH 5.5 demonstrated that the fungicide from the nanoparticles was released in a sustainable manner with a prolonged release time up to 86 h. On another note, the in vitro antifungal studies established that smaller particle size leads to lower half maximum effective concentration (EC50) value, which indicates higher antifungal activity against G. boninense.
Ketogenic Diet-Induced Weight Loss is Associated with an Increase in Vitamin D Levels in Obese Adults
Authors: Perticone Maria , Maio Raffaele , Sciacqua Angela , Suraci Edoardo , Pinto Angelina , Pujia Roberta , Zito Roberta , Gigliotti Simona , Sesti Giorgio , Perticone Francesco
Published: July 2019

Vitamin D is an important micronutrient involved in several processes. Evidence has shown a strong association between hypovitaminosis D and cardio-metabolic diseases, including obesity. A ketogenic diet has proven to be very effective for weight loss, especially in reducing fat mass while preserving fat-free mass. The aim of this study was to investigate the effect of a ketogenic diet-induced weight loss on vitamin D status in a population of obese adults. We enrolled 56 obese outpatients, prescribed with either traditional standard hypocaloric Mediterranean diet (SHMD) or very low-calorie ketogenic diet (VLCKD). Serum 25(OH)D concentrations were measured by chemiluminescence. The mean value of serum 25-hydroxyvitamin D (25(OH)D) concentrations in the whole population at baseline was 17.8 ± 5.6 ng/mL, without differences between groups. After 12 months of dietetic treatment, in VLCKD patients serum 25(OH)D concentrations increased from 18.4 ± 5.9 to 29.3 ± 6.8 ng/mL (p < 0.0001), vs 17.5 ± 6.1 to 21.3 ± 7.6 ng/mL (p = 0.067) in the SHMD group (for each kilogram of weight loss, 25(OH)D concentration increased 0.39 and 0.13 ng/mL in the VLCKD and in the SHMD groups, respectively). In the VLCKD group, the increase in serum 25(OH)D concentrations was strongly associated with body mass index, waist circumference, and fatty mass variation. In a multiple regression analysis, fatty mass was the strongest independent predictor of serum 25(OH)D concentration, explaining 15.6%, 3.3%, and 9.4% of its variation in the whole population, in SHMD, and VLCKD groups, respectively. We also observed a greater reduction of inflammation (evaluated by high-sensitivity C reactive protein (hsCRP) values) and a greater improvement in glucose homeostasis, confirmed by a reduction of HOMA values, in the VLCKD versus the SHMD group. Taken together, all these data suggest that a dietetic regimen, which implies a great reduction of fat mass, can improve vitamin D status in the obese.
Benzotriazine Di-Oxide Prodrugs for Exploiting Hypoxia and Low Extracellular pH in Tumors
Authors: Hay Michael P. , Shin Hong Nam , Wong Way Wua , Sahimi Wan Wan , Vaz Aaron T.D. , Yadav Pooja , Anderson Robert F. , Hicks Kevin O. , Wilson William R.
Published: July 2019

Extracellular acidification is an important feature of tumor microenvironments but has yet to be successfully exploited in cancer therapy. The reversal of the pH gradient across the plasma membrane in cells that regulate intracellular pH (pHi) has potential to drive the selective uptake of weak acids at low extracellular pH (pHe). Here, we investigate the dual targeting of low pHe and hypoxia, another key feature of tumor microenvironments. We prepared eight bioreductive prodrugs based on the benzotriazine di-oxide (BTO) nucleus by appending alkanoic or aminoalkanoic acid sidechains. The BTO acids showed modest selectivity for both low pHe (pH 6.5 versus 7.4, ratios 2 to 5-fold) and anoxia (ratios 2 to 8-fold) in SiHa and FaDu cell cultures. Related neutral BTOs were not selective for acidosis, but had greater cytotoxic potency and hypoxic selectivity than the BTO acids. Investigation of the uptake and metabolism of representative BTO acids confirmed enhanced uptake at low pHe, but lower intracellular concentrations than expected for passive diffusion. Further, the modulation of intracellular reductase activity and competition by the cell-excluded electron acceptor WST-1 suggests that the majority of metabolic reductions of BTO acids occur at the cell surface, compromising the engagement of the resulting free radicals with intracellular targets. Thus, the present study provides support for designing bioreductive prodrugs that exploit pH-dependent partitioning, suggesting, however, that that the approach should be applied to prodrugs with obligate intracellular activation.
Curcumin Combination Chemotherapy: The Implication and Efficacy in Cancer
Authors: Tan Bee Ling , Norhaizan Mohd Esa
Published: July 2019

Many chemotherapeutic drugs have been used for the treatment of cancer, for instance, doxorubicin, irinotecan, 5-fluorouracil, cisplatin, and paclitaxel. However, the effectiveness of chemotherapy is limited in cancer therapy due to drug resistance, therapeutic selectivity, and undesirable side effects. The combination of therapies with natural compounds is likely to increase the effectiveness of drug treatment as well as reduce the adverse outcomes. Curcumin, a polyphenolic isolated from Curcuma longa, belongs to the rhizome of Zingiberaceae plants. Studies from in vitro and in vivo revealed that curcumin exerts many pharmacological activities with less toxic effects. The biological mechanisms underlying the anticancer activity of co-treatment curcumin and chemotherapy are complex and worth to discuss further. Therefore, this review aimed to address the molecular mechanisms of combined curcumin and chemotherapy in the treatment of cancer. The anticancer activity of combined nanoformulation of curcumin and chemotherapy was also discussed in this study. Taken together, a better understanding of the implication and underlying mechanisms of action of combined curcumin and chemotherapy may provide a useful approach to combat cancer diseases.
Occurrence of Campylobacter jejuni and Campylobacter coli in Cattle and Sheep in Northern Spain and Changes in Antimicrobial Resistance in Two Studies 10-years Apart
Authors: Ocejo Medelin , Oporto Beatriz , Hurtado Ana
Published: July 2019

A cross-sectional survey was conducted in 2014–2016 in 301 ruminant herds to estimate C. jejuni and C. coli prevalence, and investigate their susceptibility to antimicrobials. Risk of shedding C. jejuni was higher in cattle than sheep (81.2% vs. 45.2%; ORadj = 5.22, p < 0.001), whereas risk of shedding C. coli was higher in sheep than in cattle (19.1% vs. 11.3%; ORadj = 1.71, p = 0.128). Susceptibility to six antimicrobials was determined by broth microdilution using European Committee for Antimicrobial Susceptibility Testing (EUCAST) epidemiological cut-off values. C. coli exhibited higher resistance (94.1%, 32/34) than C. jejuni (65.1%, 71/109), and resistance was more widespread in isolates from dairy cattle than beef cattle or sheep. Compared to results obtained 10-years earlier (2003–2005) in a similar survey, an increase in fluoroquinolone-resistance was observed in C. jejuni from beef cattle (32.0% to 61.9%; OR = 3.45, p = 0.020), and a decrease in tetracycline-resistance in C. jejuni from dairy cattle (75.0% to 43.2%; OR = 0.25, p = 0.026). Resistance to macrolides remained stable at low rates and restricted to C. coli from dairy cattle, with all macrolide-resistant C. coli showing a pattern of pan-resistance. Presence of the single nucleotide polymorphisms (SNPs) associated to quinolone and macrolide resistance was confirmed in all phenotypically resistant isolates. The increase in fluoroquinolone resistance is worrisome but susceptibility to macrolides is reassuring.
Study on Wear Properties of the Flow Parts in a Centrifugal Pump Based on EDEM–Fluent Coupling
Authors: Huang Si , Huang Jiaxing , Guo Jiawei , Mo Yushi
Published: July 2019

By using EDEM–Fluent codes and coupling the continuous fluid medium with a solid particle discrete element, the solid–liquid two-phase flow field in a centrifugal pump was simulated under the same inlet conditions of the particle volume fraction and three flow conditions of 0.7Qd, 1.0Qd and 1.3Qd. By introducing the Archard wear model, the wear was calculated, and the wear law was obtained for the pump flow parts such as the leading edge of the impeller blade, blade tip, blade pressure side, blade suction side, impeller shroud, hub and volute. The results demonstrate that the wear of volute is about 70% of the total wear of pump. The wear in the impeller mainly occurs in the blade leading edge, the junction of the hub and the trailing part of the blade pressure side, and the junction of the shroud and the rear part of the blade suction side. Under lower flow conditions, the wear in the impeller shroud is relatively considerable. As the flow rate increases, the wear in the blade pressure side and the hub increases significantly.
Isolation Process and Compound Identification of Agarwood Essential Oils from Aquilaria crassna Cultivated at Three Different Locations in Vietnam
Authors: Thuy Dinh Thi Thu , Tuyen Tran Thi , Thuy Tran Thi Thu , Minh Pham Thi Hong , Tran Quoc Toan , Long Pham Quoc , Nguyen Duy Chinh , Bach Long Giang , Chien Nguyen Quyet
Published: July 2019

Agarwood and agarwood essential oils are commodities with great commercial value. In Vietnam, the agarwood industry has been growing, with more than 10,000 ha of forest land reserved for the cultivation of Aquilaria crassna, an agarwood-producing tree. The aim of this study was to present a hydrodistillation process to recover agarwood essential oil and to compare chemical compositions of agarwood samples harvested from various locations in Vietnam. Three agarwood samples representing products from A. crassna trees cultivated in the provinces of Bac Giang and Khanh Hoa, and on the Phu Quoc island (Kien Giang province) of Vietnam were subjected to hydrodistillation, resulting in essential oil yields of 0.32%, 0.27%, and 0.25% (w/w), respectively. Using GC–MS analysis, a total of 44 volatile compounds were identified in the obtained oils. Most of the constituents were oxygenated sesquiterpenes and had been previously found in other agarwood oil samples. Notable compounds of other chemical classes were aromatics and fatty acids. The three oil samples showed a common volatile profile, which is characterized by the dominance of eremophilane, agarofurans, and eudesmane sesquiterpenes, while vetispirane and guaiane sesquiterpenes were found in smaller quantities. Desired compounds, such as neopetasane (7.47–8.29%), dihydrokaranone (2.63–3.59%), β-agarofuran (3.04–6.18%), and agarospirol (2.98–3.42%), were present in substantial quantities, suggesting that the essential oils could be commercialized as fragrant materials of high value.
PEM Fuel Cell Voltage Neural Control Based on Hydrogen Pressure Regulation
Authors: Morán-Durán Andrés , Martínez-Sibaja Albino , Rodríguez-Jarquin José Pastor , Posada-Gómez Rubén , González Oscar Sandoval
Published: July 2019

Fuel cells are promising devices to transform chemical energy into electricity; their behavior is described by principles of electrochemistry and thermodynamics, which are often difficult to model mathematically. One alternative to overcome this issue is the use of modeling methods based on artificial intelligence techniques. In this paper is proposed a hybrid scheme to model and control fuel cell systems using neural networks. Several feature selection algorithms were tested for dimensionality reduction, aiming to eliminate non-significant variables with respect to the control objective. Principal component analysis (PCA) obtained better results than other algorithms. Based on these variables, an inverse neural network model was developed to emulate and control the fuel cell output voltage under transient conditions. The results showed that fuel cell performance does not only depend on the supply of the reactants. A single neuro-proportional–integral–derivative (neuro-PID) controller is not able to stabilize the output voltage without the support of an inverse model control that includes the impact of the other variables on the fuel cell performance. This practical data-driven approach is reliably able to reduce the cost of the control system by the elimination of non-significant measures.
An Analysis of Operational Efficiencies in the Waste-to-Energy (WTE) Plants of Kaohsiung Municipality (Taiwan)
Authors: Tsai Wen-Tien
Published: July 2019

As the second-largest city in Taiwan, the Kaohsiung municipality has faced serious environmental loadings in recent decades. Among them, waste management is a key issue because of large amount of urban and industrial waste produced daily. In this regard, waste-to-energy (WTE) systems adopting the best available control technology for air pollution is a win-win approach because it also generates electricity to mitigate the dependence on imported fossil fuels and the greenhouse gas emissions incidentally. In this work, the updated status of municipal solid waste (MSW) and WTE plants in Kaohsiung were analyzed to get the crux based on the official database. Using the operational data on the WTE plants over recent years (2003–2018), the analysis of operational efficiencies for the four WTE plants in Kaohsiung was addressed in the paper. It showed that their operational efficiencies, ranging from 0.287 to 0.568 kW-h/kg, indicated an approximate “bathtub curve” pattern. In addition, analyzing the project for revamping the Gangshan WTE plant showed a significant progress in operational efficiencies with a significant increase from 0.506 kW-h/kg in 2016 to 0.587 kW-h/kg in 2018. Finally, some recommendations on technological measures and regulatory incentives for upgrading the operational efficiencies of existing WTE plants were addressed in the work.