bluuebunny/crossref_metadata_2025 huggingface dataset:
A Molecular Basis for Reciprocal Regulation between Pheromones and Hormones in Response to Dietary Cues in C. elegans
Authors: Park Saeram , Park Jun Young , Paik Young-Ki
Published: April 2020

Under stressful conditions, the early larvae of C. elegans enter dauer diapause, a non-aging period, driven by the seemingly opposite influence of ascaroside pheromones (ASCRs) and steroid hormone dafachronic acids (DAs). However, the molecular basis of how these small molecules engage in competitive crosstalk in coordination with insulin/IGF-1 signaling (IIS) remains elusive. Here we report a novel transcriptional regulatory pathway that seems to operate between the ASCR and DA biosynthesis under ad libitum (AL) feeding conditions or bacterial deprivation (BD). Although expression of the ASCR and DA biosynthetic genes reciprocally inhibit each other, ironically and interestingly, such dietary cue-mediated modulation requires the presence of the competitors. Under BD, induction of ASCR biosynthetic gene expression required DA, while ASCR suppresses the expression of the DA biosynthetic gene daf-36. The negative regulation of DA by ASCR was IIS-dependent, whereas daf-36 regulation appeared to be independent of IIS. These observations suggest that the presence of ASCR determines the IIS-dependency of DA gene expression regardless of dietary conditions. Thus, our work defines a molecular basis for a novel reciprocal gene regulation of pheromones and hormones to cope with stressful conditions during development and aging.
Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma
Authors: Petrova Vera , Arkhypov Ihor , Weber Rebekka , Groth Christopher , Altevogt Peter , Utikal Jochen , Umansky Viktor
Published: April 2020

Although melanoma is one of the most immunogenic tumors, it has an ability to evade anti-tumor immune responses by exploiting tolerance mechanisms, including negative immune checkpoint molecules. The most extensively studied checkpoints represent cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Immune checkpoint inhibitors (ICI), which were broadly applied for melanoma treatment in the past decade, can unleash anti-tumor immune responses and result in melanoma regression. Patients responding to the ICI treatment showed long-lasting remission or disease control status. However, a large group of patients failed to respond to this therapy, indicating the development of resistance mechanisms. Among them are intrinsic tumor properties, the dysfunction of effector cells, and the generation of immunosuppressive tumor microenvironment (TME). This review discusses achievements of ICI treatment in melanoma, reasons for its failure, and promising approaches for overcoming the resistance. These methods include combinations of different ICI with each other, strategies for neutralizing the immunosuppressive TME and combining ICI with other anti-cancer therapies such as radiation, oncolytic viral, or targeted therapy. New therapeutic approaches targeting other immune checkpoint molecules are also discussed.
Modulatory Effects of Silymarin on Benzo[a]pyrene-Induced Hepatotoxicity
Authors: Jee Seung-Cheol , Kim Min , Sung Jung-Suk
Published: April 2020

Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon, is a group 1 carcinogen that introduces mutagenic DNA adducts into the genome. In this study, we investigated the molecular mechanisms underlying the involvement of silymarin in the reduction of DNA adduct formation by B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), induced by B[a]P. B[a]P exhibited toxicity in HepG2 cells, whereas co-treatment of the cells with B[a]P and silymarin reduced the formation of BPDE-DNA adducts, thereby increasing cell viability. Determination of the level of major B[a]P metabolites in the treated cells showed that BPDE levels were reduced by silymarin. Nuclear factor erythroid 2-related factor 2 (Nrf2) and pregnane X receptor (PXR) were found to be involved in the activation of detoxifying genes against B[a]P-mediated toxicity. Silymarin did not increase the expression of these major transcription factors, but greatly facilitated their nuclear translocation. In this manner, treatment of HepG2 cells with silymarin modulated detoxification enzymes through NRF2 and PXR to eliminate B[a]P metabolites. Knockdown of Nrf2 abolished the preventive effect of silymarin on BPDE-DNA adduct formation, indicating that activation of the Nrf2 pathway plays a key role in preventing B[a]P-induced genotoxicity. Our results suggest that silymarin has anti-genotoxic effects, as it prevents BPDE-DNA adduct formation by modulating the Nrf2 and PXR signaling pathways.
Photobiomodulation Mediates Neuroprotection against Blue Light Induced Retinal Photoreceptor Degeneration
Authors: Heinig Nora , Schumann Ulrike , Calzia Daniela , Panfoli Isabella , Ader Marius , Schmidt Mirko H. H. , Funk Richard H. W. , Roehlecke Cora
Published: April 2020

Potent neuroprotective effects of photobiomodulation with 670 nm red light (RL) have been demonstrated in several models of retinal disease. RL improves mitochondrial metabolism, reduces retinal inflammation and oxidative cell stress, showing its ability to enhance visual function. However, the current knowledge is limited to the main hypothesis that the respiratory chain complex IV, cytochrome c oxidase, serves as the primary target of RL. Here, we demonstrate a comprehensive cellular, molecular, and functional characterization of neuroprotective effects of 670 nm RL and 810 nm near-infrared light (NIRL) on blue light damaged murine primary photoreceptors. We show that respiratory chain complexes I and II are additional PBM targets, besides complex IV, leading to enhanced mitochondrial energy metabolism. Accordingly, our study identified mitochondria related RL- and NIRL-triggered defense mechanisms promoting photoreceptor neuroprotection. The observed improvement of mitochondrial and extramitochondrial respiration in both inner and outer segments is linked with reduced oxidative stress including its cellular consequences and reduced mitochondria-induced apoptosis. Analysis of regulatory mechanisms using gene expression analysis identified upregulation α-crystallins that indicate enhanced production of proteins with protective functions that point to the rescued mitochondrial function. The results support the hypothesis that energy metabolism is a major target for retinal light therapy.
Hepatic Lipid Catabolism via PPARα-Lysosomal Crosstalk
Authors: Sinha Rohit A. , Rajak Sangam , Singh Brijesh K. , Yen Paul M.
Published: April 2020

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors which belong to the nuclear hormone receptor superfamily. They regulate key aspects of energy metabolism within cells. Recently, PPARα has been implicated in the regulation of autophagy-lysosomal function, which plays a key role in cellular energy metabolism. PPARα transcriptionally upregulates several genes involved in the autophagy-lysosomal degradative pathway that participates in lipolysis of triglycerides within the hepatocytes. Interestingly, a reciprocal regulation of PPARα nuclear action by autophagy-lysosomal activity also exists with implications in lipid metabolism. This review succinctly discusses the unique relationship between PPARα nuclear action and lysosomal activity and explores its impact on hepatic lipid homeostasis under pathological conditions such as non-alcoholic fatty liver disease (NAFLD).
Comparative Proteomic Analysis by iTRAQ Reveals that Plastid Pigment Metabolism Contributes to Leaf Color Changes in Tobacco (Nicotiana tabacum) during Curing
Authors: Wu Shengjiang , Guo Yushuang , Adil Muhammad Faheem , Sehar Shafaque , Cai Bin , Xiang Zhangmin , Tu Yonggao , Zhao Degang , Shamsi Imran Haider
Published: April 2020

Tobacco (Nicotiana tabacum), is a world’s major non-food agricultural crop widely cultivated for its economic value. Among several color change associated biological processes, plastid pigment metabolism is of trivial importance in postharvest plant organs during curing and storage. However, the molecular mechanisms involved in carotenoid and chlorophyll metabolism, as well as color change in tobacco leaves during curing, need further elaboration. Here, proteomic analysis at different curing stages (0 h, 48 h, 72 h) was performed in tobacco cv. Bi’na1 with an aim to investigate the molecular mechanisms of pigment metabolism in tobacco leaves as revealed by the iTRAQ proteomic approach. Our results displayed significant differences in leaf color parameters and ultrastructural fingerprints that indicate an acceleration of chloroplast disintegration and promotion of pigment degradation in tobacco leaves due to curing. In total, 5931 proteins were identified, of which 923 (450 up-regulated, 452 down-regulated, and 21 common) differentially expressed proteins (DEPs) were obtained from tobacco leaves. To elucidate the molecular mechanisms of pigment metabolism and color change, 19 DEPs involved in carotenoid metabolism and 12 DEPs related to chlorophyll metabolism were screened. The results exhibited the complex regulation of DEPs in carotenoid metabolism, a negative regulation in chlorophyll biosynthesis, and a positive regulation in chlorophyll breakdown, which delayed the degradation of xanthophylls and accelerated the breakdown of chlorophylls, promoting the formation of yellow color during curing. Particularly, the up-regulation of the chlorophyllase-1-like isoform X2 was the key protein regulatory mechanism responsible for chlorophyll metabolism and color change. The expression pattern of 8 genes was consistent with the iTRAQ data. These results not only provide new insights into pigment metabolism and color change underlying the postharvest physiological regulatory networks in plants, but also a broader perspective, which prompts us to pay attention to further screen key proteins in tobacco leaves during curing.
Treatment of Cystic Fibrosis Patients Homozygous for F508del with Lumacaftor-Ivacaftor (Orkambi®) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells
Authors: Favia Maria , Gallo Crescenzio , Guerra Lorenzo , De Venuto Domenica , Diana Anna , Polizzi Angela Maria , Montemurro Pasqualina , Mariggiò Maria Addolorata , Leonetti Giuseppina , Manca Antonio , Casavola Valeria , Conese Massimo
Published: April 2020

The treatment of cystic fibrosis (CF) patients homozygous for the F508del mutation with Orkambi®, a combination of a corrector (lumacaftor) and a potentiator (ivacaftor) of the mutated CFTR protein, resulted in some amelioration of the respiratory function. However, a great variability in the clinical response was also observed. The aim of this study was to evaluate the response to Orkambi® in a small cohort of F508del/F508del patients (n = 14) in terms of clinical and laboratory parameters, including ex vivo CFTR activity in mononuclear cells (MNCs), during a 12-month treatment. Patients responded with an increase in percent predicted forced expiratory volume in 1 s (FEV1%) and body mass index (BMI) as well as with a decrease in white blood cell (WBC) total counts and serum C-reactive protein (CRP) levels, although not significantly. Sweat chloride and CFTR-dependent chloride efflux were found to decrease and increase, respectively, as compared with pre-therapy values. CFTR and BMI showed a statistically significant correlation during Orkambi® treatment. Clustering analysis showed that CFTR, BMI, sweat chloride, FEV1%, and WBC were strongly associated. These data support the notion that CFTR-dependent chloride efflux in MNCs should be investigated as a sensitive outcome measure of Orkambi® treatment in CF patients.
Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach
Authors: Ghassem-Zadeh Sahar , Hufnagel Katrin , Bauer Andrea , Frossard Jean-Louis , Yoshida Masaru , Kutsumi Hiromu , Acha-Orbea Hans , Neulinger-Muñoz Matthias , Vey Johannes , Eckert Christoph , Strobel Oliver , Hoheisel Jörg D. , Felix Klaus
Published: April 2020

Identification of disease-associated autoantibodies is of high importance. Their assessment could complement current diagnostic modalities and assist the clinical management of patients. We aimed at developing and validating high-throughput protein microarrays able to screen patients’ sera to determine disease-specific autoantibody-signatures for pancreatic cancer (PDAC), chronic pancreatitis (CP), autoimmune pancreatitis and their subtypes (AIP-1 and AIP-2). In-house manufactured microarrays were used for autoantibody-profiling of IgG-enriched preoperative sera from PDAC-, CP-, AIP-1-, AIP-2-, other gastrointestinal disease (GID) patients and healthy controls. As a top-down strategy, three different fluorescence detection-based protein-microarrays were used: large with 6400, intermediate with 345, and small with 36 full-length human recombinant proteins. Large-scale analysis revealed 89 PDAC, 98 CP and 104 AIP immunogenic antigens. Narrowing the selection to 29 autoantigens using pooled sera first and individual sera afterwards allowed a discrimination of CP and AIP from PDAC. For validation, predictive models based on the identified antigens were generated which enabled discrimination between PDAC and AIP-1 or AIP-2 yielded high AUC values of 0.940 and 0.925, respectively. A new repertoire of autoantigens was identified and their assembly as a multiplex test will provide a fast and cost-effective tool for differential diagnosis of pancreatic diseases with high clinical relevance.
Novel Osteogenic Behaviors around Hydrophilic and Radical-Free 4-META/MMA-TBB: Implications of an Osseointegrating Bone Cement
Authors: Sugita Yoshihiko , Okubo Takahisa , Saita Makiko , Ishijima Manabu , Torii Yasuyoshi , Tanaka Miyuki , Iwasaki Chika , Sekiya Takeo , Tabuchi Masako , Mohammadzadeh Rezaei Naser , Taniyama Takashi , Sato Nobuaki , Saruta Juri , Hasegawa Masakazu , Hirota Makoto , Park Wonhee , Lee Masaichi Chang-Il , Maeda Hatsuhiko , Ogawa Takahiro
Published: April 2020

Poly(methyl methacrylate) (PMMA)-based bone cement, which is widely used to affix orthopedic metallic implants, is considered bio-tolerant but lacks osteoconductivity and is cytotoxic. Implant loosening and toxic complications are significant and recognized problems. Here we devised two strategies to improve PMMA-based bone cement: (1) adding 4-methacryloyloxylethyl trimellitate anhydride (4-META) to MMA monomer to render it hydrophilic; and (2) using tri-n-butyl borane (TBB) as a polymerization initiator instead of benzoyl peroxide (BPO) to reduce free radical production. Rat bone marrow-derived osteoblasts were cultured on PMMA-BPO, common bone cement ingredients, and 4-META/MMA-TBB, newly formulated ingredients. After 24 h of incubation, more cells survived on 4-META/MMA-TBB than on PMMA-BPO. The mineralized area was 20-times greater on 4-META/MMA-TBB than PMMA-BPO at the later culture stage and was accompanied by upregulated osteogenic gene expression. The strength of bone-to-cement integration in rat femurs was 4- and 7-times greater for 4-META/MMA-TBB than PMMA-BPO during early- and late-stage healing, respectively. MicroCT and histomorphometric analyses revealed contact osteogenesis exclusively around 4-META/MMA-TBB, with minimal soft tissue interposition. Hydrophilicity of 4-META/MMA-TBB was sustained for 24 h, particularly under wet conditions, whereas PMMA-BPO was hydrophobic immediately after mixing and was unaffected by time or condition. Electron spin resonance (ESR) spectroscopy revealed that the free radical production for 4-META/MMA-TBB was 1/10 to 1/20 that of PMMA-BPO within 24 h, and the substantial difference persisted for at least 10 days. The compromised ability of PMMA-BPO in recruiting cells was substantially alleviated by adding free radical-scavenging amino-acid N-acetyl cysteine (NAC) into the material, whereas adding NAC did not affect the ability of 4-META/MMA-TBB. These results suggest that 4-META/MMA-TBB shows significantly reduced cytotoxicity compared to PMMA-BPO and induces osteoconductivity due to uniquely created hydrophilic and radical-free interface. Further pre-clinical and clinical validations are warranted.
Inhibitory Effective Perturbations of Cilobradine (DK-AH269), A Blocker of HCN Channels, on the Amplitude and Gating of Both Hyperpolarization-Activated Cation and Delayed-Rectifier Potassium Currents
Authors: Lu Te-Ling , Lu Te-Jung , Wu Sheng-Nan
Published: April 2020

Cilobradine (CIL, DK-AH269), an inhibitor of hyperpolarization-activated cation current (Ih), has been observed to possess pro-arrhythmic properties. Whether and how CIL is capable of perturbing different types of membrane ionic currents existing in electrically excitable cells, however, is incompletely understood. In this study, we intended to examine possible modifications by it or other structurally similar compounds of ionic currents in pituitary tumor (GH3) cells and in heart-derived H9c2 cells. The standard whole-cell voltage-clamp technique was performed to examine the effect of CIL on ionic currents. GH3-cell exposure to CIL suppressed the density of hyperpolarization-evoked Ih in a concentration-dependent manner with an effective IC50 of 3.38 μM. Apart from its increase in the activation time constant of Ih during long-lasting hyperpolarization, the presence of CIL (3 μM) distinctly shifted the steady-state activation curve of Ih triggered by a 2-s conditioning pulse to a hyperpolarizing direction by 10 mV. As the impedance-frequency relation of Ih was studied, its presence raised the impedance magnitude at the resonance frequency induced by chirp voltage. CIL also suppressed delayed-rectifier K+ current (IK(DR)) followed by the accelerated inactivation time course of this current, with effective IC50 (measured at late IK(DR)) or KD value of 3.54 or 3.77 μM, respectively. As the CIL concentration increased 1 to 3 μM, the inactivation curve of IK(DR) elicited by 1- or 10-s conditioning pulses was shifted to a hyperpolarizing potential by approximately 10 mV, and the recovery of IK(DR) inactivation during its presence was prolonged. The peak Na+ current (INa) during brief depolarization was resistant to being sensitive to the presence of CIL, yet to be either decreased by subsequent addition of A-803467 or enhanced by that of tefluthrin. In cardiac H9c2 cells, unlike the CIL effect, the addition of either ivabradine or zatebradine mildly led to a lowering in IK(DR) amplitude with no conceivable change in the inactivation time course of the current. Taken together, the compound like CIL, which was tailored to block hyperpolarization-activated cation (HCN) channels effectively, was also capable of altering the amplitude and gating of IK(DR), thereby influencing the functional activities of electrically excitable cells, such as GH3 cells.
Antxr1, Which is a Target of Runx2, Regulates Chondrocyte Proliferation and Apoptosis
Authors: Jiang Qing , Qin Xin , Yoshida Carolina Andrea , Komori Hisato , Yamana Kei , Ohba Shinsuke , Hojo Hironori , Croix Brad St. , Kawata-Matsuura Viviane K. S. , Komori Toshihisa
Published: April 2020

Antxr1/Tem8 is highly expressed in tumor endothelial cells and is a receptor for anthrax toxin. Mutation of Antxr1 causes GAPO syndrome, which is characterized by growth retardation, alopecia, pseudo-anodontia, and optic atrophy. However, the mechanism underlying the growth retardation remains to be clarified. Runx2 is essential for osteoblast differentiation and chondrocyte maturation and regulates chondrocyte proliferation through Ihh induction. In the search of Runx2 target genes in chondrocytes, we found that Antxr1 expression is upregulated by Runx2. Antxr1 was highly expressed in cartilaginous tissues and was directly regulated by Runx2. In skeletal development, the process of endochondral ossification proceeded similarly in wild-type and Antxr1–/– mice. However, the limbs of Antxr1–/– mice were shorter than those of wild-type mice from embryonic day 16.5 due to the reduced chondrocyte proliferation. Chondrocyte-specific Antxr1 transgenic mice exhibited shortened limbs, although the process of endochondral ossification proceeded as in wild-type mice. BrdU-uptake and apoptosis were both increased in chondrocytes, and the apoptosis-high regions were mineralized. These findings indicated that Antxr1, of which the expression is regulated by Runx2, plays an important role in chondrocyte proliferation and that overexpression of Antxr1 causes chondrocyte apoptosis accompanied by matrix mineralization.
A Chiral Bis(salicylaldiminato)zinc(II) Complex with Second-Order Nonlinear Optical and Luminescent Properties in Solution
Authors: Matozzo Paola , Colombo Alessia , Dragonetti Claudia , Righetto Stefania , Roberto Dominique , Biagini Paolo , Fantacci Simona , Marinotto Daniele
Published: April 2020

Whereas there is an increasing amount of reports on the second-order nonlinear optical (NLO) and luminescence properties of tetradentate [N2O2] Schiff base–zinc complexes, the study of zinc complexes having two bidentate [NO] Schiff-base ligands is relatively unexplored from an NLO point of view. This work puts in evidence that the known chiral bis{2-[(R)-(+)-1-phenylethyliminomethyl]phenolato-N,O}zinc(II) complex is a fascinating multifunctional molecular inorganic–organic hybrid material characterized by interesting second-order NLO and luminescent properties in solution. The emissive properties of the organic 2-(R)-(+)-1-phenylethyliminomethyl]phenol proligand are greatly enhanced upon coordination to the inorganic Zn(II) center.
Abundance and Distribution of Korean Flower Flies (Diptera: Syrphidae): Dominant Influence of Latitude on Regional Distribution
Authors: Kwon Tae-Sung , Lee Cheol Min , Ji Ok Yeong , Athar Mohammad , Jung Sung Cheol , Lim Jong-Hwan , Park Young-Seuk
Published: April 2020

Studies on abundance and distribution at different scales are rare. We examined whether the abundance of flower flies at a site in South Korea was related to the national occupancy and global distribution (distributional extent or range size) and whether the national occupancy was related to global distribution. In global distribution, the influence of two dimensions (latitude and longitude) was analyzed separately. Flower flies were collected by malaise and pitfall traps at a forest gap in South Korea. Data regarding national occupancy and global distribution were obtained from a Korean Flower Fly Atlas. We collected 46 species from the field survey and obtained a list of 119 species from the Korean Flower Fly Atlas. Our results showed that abundance at a site was positively correlated with national occupancy, but not global distribution, and the national occupancy was positively correlated with global distribution, mainly by the latitudinal range size. Finally, our results indicated that the regional distribution of flower flies was influenced by its one-dimensional global distribution.
Finding a Balance: A Systematic Review of the Biomechanical Effects of Vestibular Prostheses on Stability in Humans
Authors: Haxby Felix , Akrami Mohammad , Zamani Reza
Published: April 2020

The vestibular system is located in the inner ear and is responsible for maintaining balance in humans. Bilateral vestibular dysfunction (BVD) is a disorder that adversely affects vestibular function. This results in symptoms such as postural imbalance and vertigo, increasing the incidence of falls and worsening quality of life. Current therapeutic options are often ineffective, with a focus on symptom management. Artificial stimulation of the vestibular system, via a vestibular prosthesis, is a technique being explored to restore vestibular function. This review systematically searched for literature that reported the effect of artificial vestibular stimulation on human behaviours related to balance, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) technique. A total of 21 papers matched the inclusion criteria of the literature search conducted using the PubMed and Web of Science databases (February 2019). The populations for these studies included both healthy adults and patients with BVD. In every paper, artificial vestibular stimulation caused an improvement in certain behaviours related to balance, although the extent of the effect varied greatly. Various behaviours were measured such as the vestibulo-ocular reflex, postural sway and certain gait characteristics. Two classes of prosthesis were evaluated and both showed a significant improvement in at least one aspect of balance-related behaviour in every paper included. No adverse effects were reported for prostheses using noisy galvanic vestibular stimulation, however, prosthetic implantation sometimes caused hearing or vestibular loss. Significant heterogeneity in methodology, study population and disease aetiology were observed. The present study confirms the feasibility of vestibular implants in humans for restoring balance in controlled conditions, but more research needs to be conducted to determine their effects on balance in non-clinical settings.
Spine and TMJ: A Pathophysiology Report
Authors: Fiorillo Luca
Published: April 2020

The relationship between posture, spine, and temporomandibular joint (TMJ) is still a hotly debated topic in medicine. TMJ takes part in different physiological functions of the organism, starting from its embryological development, it is possible that it influences different vital functions. There is a strong connection between the respiratory tract and dental/maxillary occlusion or anatomy. The altered physiology of this district leads to pathologies that could affect the whole organism. On the contrary, it is also possible to highlight some symptoms of distant organism districts. Knowing well the pathophysiology of this district and semiotics, it is also possible to diagnose pathologies affecting other organs.
Color Image Complexity versus Over-Segmentation: A Preliminary Study on the Correlation between Complexity Measures and Number of Segments
Authors: Ivanovici Mihai , Coliban Radu-Mihai , Hatfaludi Cosmin , Nicolae Irina Emilia
Published: April 2020

It is said that image segmentation is a very difficult or complex task. First of all, we emphasize the subtle difference between the notions of difficulty and complexity. Then, in this article, we focus on the question of how two widely used color image complexity measures correlate with the number of segments resulting in over-segmentation. We study the evolution of both the image complexity measures and number of segments as the image complexity is gradually decreased by means of low-pass filtering. In this way, we tackle the possibility of predicting the difficulty of color image segmentation based on image complexity measures. We analyze the complexity of images from the point of view of color entropy and color fractal dimension and for color fractal images and the Berkeley data set we correlate these two metrics with the segmentation results, more specifically the number of quasi-flat zones and the number of JSEG regions in the resulting segmentation map. We report on our experimental results and draw conclusions.
Micro-Alloying and Surface Texturing of Ti-6Al-4V Alloy by Embedding Nanoparticles Using Gas Tungsten Arc Welding
Authors: Cooke Kavian Omar , Shar Muhammad Ali , Hussain Suleman
Published: April 2020

Titanium alloy Ti-6Al-4V is known for both its excellent mechanical properties and its low surface hardness. This study explores a two-step process for depositing a hard nanocrystalline coating onto the surface of the Ti-alloy, followed by surface melting, which embeds hard nanoparticles into a thin surface layer of the alloy. The treated surface layer was studied using X-ray diffraction, scanning electron microscopy, and Vicker’s micro-hardness testing. The results of the study show that the surface of the Ti-6Al-4V alloy can be successfully hardened by embedding nanosized Al2O3 particles into the surface using gas tungsten arc welding to melt the surface of the material. Surface melting the Ti-6Al-4V alloy with a 50A welding current produced the maximum microhardness of 701 HV0.2kg. The micro-hardness of the treated surface layer decreased with the increasing size of the nanoparticles, while the roughness of the surface increased with the increasing welding current. The heat input into the surface during the surface melting process resulted in the formation of various intermetallic compounds capable of further increasing the hardness of the Ti-6Al-4V surface.
Design and Simulation of a New Intermodal Automated Container Transport System (ACTS) Considering Different Operation Scenarios of Container Terminals
Authors: Hur Sung-Ho , Lee Chaeyoung , Roh Hong-Seung , Park Sebeom , Choi Yosoon
Published: April 2020

In this study, we have designed a new intermodal automated container transport system (ACTS) via a roll-on/roll-off method that connects a logistics hub between a port and inland. Further, we have presented the development of a simulation model and the results of the simulator development. A simulation program was developed using a general-purpose simulation system (GPSS)/H to predict the processing capacity of the ACTS system and derive the optimum input equipment size and operation method. Additionally, the PROOF5 program was used for the visual verification of the system algorithm and for users to intuitively view and monitor events occurring in the terminal. The simulation program developed in this study can be used in the future as a tool to compare and analyze the efficiency of the existing road-transport-based system and the proposed ACTS system when the latter is implemented in a specific region.
Communicating Simulation Outputs of Mesoscale Coastal Evolution to Specialist and Non-Specialist Audiences
Authors: Payo Andres , French Jon R. , Sutherland James , A. Ellis Michael , Walkden Michael
Published: April 2020

Coastal geomorphologists and engineers worldwide are increasingly facing the non-trivial challenge of visualising and communicating mesoscale modelling assumptions, uncertainties and outcomes to both coastal specialists and decision-makers. Visualisation of simulation outcomes is a non-trivial problem because the more abstract scientific visualisation techniques favoured by specialists for data exploration and hypothesis-testing are not always as successful at engaging decision-makers and planners. In this paper, we show how the risk of simulation model outcomes becoming disconnected from more realistic visualisations of model outcomes can be minimised by using the Coastal Modelling Environment (CoastalME). CoastalME is a modelling framework for coastal mesoscale morphological modelling that can achieve close linkages between the scientific model abstractions, in the form of lines, areas and volumes, and the 3D representation of topographic and bathymetric surfaces and shallow sub-surface sediment composition. We propose and illustrate through the study case of Happisburgh (eastern England, UK), a transparent methodology to merge the required variety of data types and formats into a 3D-thickness model that is used to initialise a simulation. We conclude by highlighting some of the barriers to the adoption of the methodology proposed.
Phosphate in Virulence of Candida albicans and Candida glabrata
Authors: Köhler Julia R. , Acosta-Zaldívar Maikel , Qi Wanjun
Published: April 2020

Candida species are the most commonly isolated invasive human fungal pathogens. A role for phosphate acquisition in their growth, resistance against host immune cells, and tolerance of important antifungal medications is becoming apparent. Phosphorus is an essential element in vital components of the cell, including chromosomes and ribosomes. Producing the energy currency of the cell, ATP, requires abundant inorganic phosphate. A comparison of the network of regulators and effectors that controls phosphate acquisition and intracellular distribution, the PHO regulon, between the model yeast Saccharomyces cerevisiae, a plant saprobe, its evolutionarily close relative C. glabrata, and the more distantly related C. albicans, highlights the need to coordinate phosphate homeostasis with adenylate biosynthesis for ATP production. It also suggests that fungi that cope with phosphate starvation as they invade host tissues, may link phosphate acquisition to stress responses as an efficient mechanism of anticipatory regulation. Recent work indicates that connections among the PHO regulon, Target of Rapamycin Complex 1 signaling, oxidative stress management, and cell wall construction are based both in direct signaling links, and in the provision of phosphate for sufficient metabolic intermediates that are substrates in these processes. Fundamental differences in fungal and human phosphate homeostasis may offer novel drug targets.
Swarm-based Parallel Control of Adjacent Irregular Buildings Considering Soil–structure Interaction
Authors: Azimi Mohsen , Molaei Yeznabad Asghar
Published: April 2020

Seismic behavior of tall buildings depends upon the dynamic characteristics of the structure, as well as the base soil properties. To consider these factors, the equations of motion for a multi-story 3D building are developed to include irregularity and soil–structure interaction (SSI). Inspired by swarm intelligence in nature, a new control method, known as swarm-based parallel control (SPC), is proposed in this study to improve the seismic performance and minimize the pounding hazards, by sharing response data among the adjacent buildings at each floor level, using a wireless-sensors network (WSN). The response of individual buildings is investigated under historic earthquake loads, and the efficiencies of each different control method are compared. To verify the effectiveness of the proposed method, the numerical example of a 15-story, 3D building is modeled, and the responses are mitigated, using semi-actively controlled magnetorheological (MR) dampers employing the proposed control algorithm and fuzzy logic control (FLC), as well as the passive-on/off methods. The main discussion of this paper is the efficiency of the proposed SPC over the independent FLC during an event where one building is damaged or uncontrolled, and an active control based upon the linear quadratic regulator (LQR) is considered for the purpose of having a benchmark ideal result. Results indicate that in case of failure in the control system, as well as the damage in the structural elements, the proposed method can sense the damage in the building, and update the control forces in the other adjacent buildings, using the modified FLC, so as to avoid pounding by minimizing the responses.
Using a Social-ecological Regime Shift Approach to Understand the Transition from Livestock to Game Farming in the Eastern Cape, South Africa
Authors: Achieng Therezah , Maciejewski Kristine , Dyer Michelle , Biggs Reinette
Published: April 2020

This study explored the shift in land use from livestock farming to game farming in the Eastern Cape, South Africa, from a social-ecological regime shift perspective. A regime shift can be defined as a large, persistent change in the structure and function of the intertwined social and ecological components of a landscape. This research focused on the Amakhala game reserve as a case study to understand how the shift affected the provision of ecosystem services and human wellbeing. We used remote sensing techniques to quantify changes in vegetation and found evidence of vegetation recovery following the shift. We then conducted interviews with both landowners and farmworkers and used participatory mapping to understand their perceptions of the main drivers and social-ecological impacts of the shift in land use. Social narratives revealed stark differences in different stakeholders’ perceptions, highlighting that the change in land use had varied implications for, and were perceived differently by, different stakeholders. Farmworkers emphasized changes in social structures that weakened community bonds and erased valued connections to the land. At the same time, they increased employment of women, skills development, and increased wages as benefits of the new game farming regime. Landowners, on the other hand, indicated financial gains from the land use change. The transition therefore resulted in trade-offs that surfaced as social, economic, and cultural losses and gains. These changes, especially in social relationships and community structures, have implications for resilience and possible future pathways of development in the region.
A Bottom-Up and Top-Down Participatory Approach to Planning and Designing Local Urban Development: Evidence from an Urban University Center
Authors: Semeraro Teodoro , Nicola Zaccarelli , Lara Alejandro , Sergi Cucinelli Francesco , Aretano Roberta
Published: April 2020

The urban area is characterized by different urban ecosystems that interact with different institutional levels, including different stakeholders and decision-makers, such as public administrations and governments. This can create many institutional conflicts in planning and designing the urban space. It would arguably be ideal for an urban area to be planned like a socio-ecological system where the urban ecosystem and institutional levels interact with each other in a multi-scale analysis. This work embraces a planning process that aims at being applied to a multi-institutional level approach that is able to match different visions and stakeholders' needs, combining bottom-up and top-down participation approaches. At the urban scale, the use of this approach is sometimes criticized because it appears to increase conflicts between the different stakeholders. Starting from a case study in the Municipality of Lecce, South Italy, we apply a top-down and bottom-up participation approach to overcome conflicts at the institutional levels in the use of the urban space in the Plan of the Urban University Center. The bottom-up participation action analyzes the vision of people that frequent the urban context. After that, we share this vision in direct comparison with decision-makers to develop the planning and design solutions. The final result is a draft of the hypothetical Plan of the Urban University Center. In this way, the bottom-up and top-down approaches are useful to match the need of the community that uses the area with the vision of urban space development of decision-makers, reducing the conflicts that can arise between different institutional levels. In this study, it also emerges that the urban question is not green areas vs. new buildings, but it is important to focus on the social use of the space to develop human well-being. With the right transition of information and knowledge between different institutional levels, the bottom-up and top-down approaches help develop an operative effective transdisciplinary urban plan and design. Therefore, public participation with bottom-up and top-down approaches is not a tool to obtain maximum consensus, but mainly a moment of confrontation to better address social issues in urban planning and design.
Land Inequality Trends and Drivers
Authors: Wegerif Marc C. A. , Guereña Arantxa
Published: April 2020

Land related inequality is a central component of the wider inequality that is one of the burning issues of our society today. It affects us all and directly determines the quality of life for billions of people who depend on land and related resources for their livelihoods. This paper explores land inequality based on a wide scoping of available information and identifies the main trends and their drivers. A wider conceptualization of what constitutes land inequality is suggested in response to shifts in how power is concentrated within the agri-food system. Land inequality is the difference in the quantity and value of land people have access to, the relative strengths of their land tenure rights, and about the appropriation of value derived from the land and its use. More data gathering and research needs to be done to better understand and monitor land inequality. Despite data limitations, what can be seen globally is a growing concentration of land in larger holdings leaving the majority of farmers, along with indigenous people and other communities, with less land. As importantly, elites and large corporations are appropriating more of the value within the agri-food sector, leaving farmers and workers with a shrinking proportion of the value produced. A framework is offered to explain the self-perpetuating nature of land inequalities that involve the mutually reinforcing concentration of both wealth and power. This is an unsustainable situation that can only be effectively addressed through challenging the fundamental drivers of accumulation by the few.
Regional Economic Sustainability: Universities’ Role in Their Territories
Authors: Gallardo-Vázquez Dolores , Folgado-Fernández José A.
Published: April 2020

The sustainability of territories (e.g., regions and countries) is currently an issue that should be considered when implementing organizational strategies. The globalization, industrialization, and population growth trends observed in recent decades have forced experts to adopt a sustainable approach capable of guaranteeing that a population’s present needs can be met without compromising future generations’ well-being. Among the essential pillars of successful sustainability strategies, social development stands out as quite important, so the present study focused on it. Social development strategies include ensuring a satisfactory level of education while simultaneously fostering an adequate quality of life and long-term sustainability. Thus, this study’s objective was to gain a clearer understanding of universities’ role as promoters of education and generators of populations that become more deeply rooted in their territory of origin. One public university, the University of Extremadura in Spain, was found to play a unique, specific role in its region, as this institution has quite unique characteristics that differentiate it from other nearby universities. This study measured the regional population’s preferences by assessing an interest group’s levels of satisfaction and by observing the influence of quality and innovation on this group’s perceptions of the public university’s operations. A questionnaire was prepared and distributed electronically to all University of Extremadura students. The final sample consisted of data from 362 questionnaires, which were analyzed using structural equation modeling. The results indicated that the students’ perceptions of this institution’s innovation and quality are determinants of their satisfaction levels. In addition, this university is considered to be a reason to remain in the region, promoting residents’ sense of belonging and helping consolidate the region as a sustainable area.
Emerging Patterns of Mountain Tourism in a Dynamic Landscape: Insights from Kamikochi Valley in Japan
Authors: Chakraborty Abhik
Published: April 2020

This article analyzes the emerging contours of mountain tourism in a highly popular destination in the North Japan Alps by reporting the findings of a two-year long study at the Kamikochi Valley. The main aim was to understand the dynamic character of the biophysical landscape and the perceptions of tourism service providers and visitors. The study was conducted using a qualitative design and involved in-depth interviews, observations, and a questionnaire survey for visitors. It was found that while different stakeholders held different perceptions of the landscape, there was a general lack of understanding among tourism service providers and visitors regarding the relationship between long-term processes and fine-scale heterogeneity of the landscape. The prevalence of an engineering approach has led to sweeping changes of key landscape interaction pathways over the years, threatening the heterogeneity and resilience of the natural environment. The findings also indicate a general visitor demand of information on the biophysical environment, and therefore it is of urgent need to address the biophysical integrity of such landscapes, and raise visitor awareness through the provision of relevant information.
Collaborative Optimization of Density and Surface Roughness of 316L Stainless Steel in Selective Laser Melting
Authors: Deng Yong , Mao Zhongfa , Yang Nan , Niu Xiaodong , Lu Xiangdong
Published: April 2020

Although the concept of additive manufacturing has been proposed for several decades, momentum in the area of selective laser melting (SLM) is finally starting to build. In SLM, density and surface roughness, as the important quality indexes of SLMed parts, are dependent on the processing parameters. However, there are few studies on their collaborative optimization during SLM to obtain high relative density and low surface roughness simultaneously in the literature. In this work, the response surface method was adopted to study the influences of different processing parameters (laser power, scanning speed and hatch space) on density and surface roughness of 316L stainless steel parts fabricated by SLM. A statistical relationship model between processing parameters and manufacturing quality is established. A multi-objective collaborative optimization strategy considering both density and surface roughness is proposed. The experimental results show that the main effects of processing parameters on the density and surface roughness are similar. We observed that the laser power and scanning speed significantly affected the above objective quality, but the influence of the hatch spacing was comparatively low. Based on the above optimization, 316L stainless steel parts with excellent surface roughness and relative density can be obtained by SLM with optimized processing parameters.
Generalized Structure Preserving Preconditioners for Frame-Based Image Deblurring
Authors: Bianchi Davide , Buccini Alessandro
Published: April 2020

We are interested in fast and stable iterative regularization methods for image deblurring problems with space invariant blur. The associated coefficient matrix has a Block Toeplitz Toeplitz Blocks (BTTB) like structure plus a small rank correction depending on the boundary conditions imposed on the imaging model. In the literature, several strategies have been proposed in the attempt to define proper preconditioner for iterative regularization methods that involve such linear systems. Usually, the preconditioner is chosen to be a Block Circulant with Circulant Blocks (BCCB) matrix because it can efficiently exploit Fast Fourier Transform (FFT) for any computation, including the (pseudo-)inversion. Nevertheless, for ill-conditioned problems, it is well known that BCCB preconditioners cannot provide a strong clustering of the eigenvalues. Moreover, in order to get an effective preconditioner, it is crucial to preserve the structure of the coefficient matrix. On the other hand, thresholding iterative methods have been recently successfully applied to image deblurring problems, exploiting the sparsity of the image in a proper wavelet domain. Motivated by the results of recent papers, the main novelty of this work is combining nonstationary structure preserving preconditioners with general regularizing operators which hold in their kernel the key features of the true solution that we wish to preserve. Several numerical experiments shows the performances of our methods in terms of quality of the restorations.