bluuebunny/crossref_metadata_2025 huggingface dataset:
PROTACs: great opportunities for academia and industry
Authors: Sun Xiuyun , Gao Hongying , Yang Yiqing , He Ming , Wu Yue , Song Yugang , Tong Yan , Rao Yu
Published: December 2019

Although many kinds of therapies are applied in the clinic, drug-resistance is a major and unavoidable problem. Another disturbing statistic is the limited number of drug targets, which are presently only 20–25% of all protein targets that are currently being studied. Moreover, the focus of current explorations of targets are their enzymatic functions, which ignores the functions from their scaffold moiety. As a promising and appealing technology, PROteolysis TArgeting Chimeras (PROTACs) have attracted great attention both from academia and industry for finding available approaches to solve the above problems. PROTACs regulate protein function by degrading target proteins instead of inhibiting them, providing more sensitivity to drug-resistant targets and a greater chance to affect the nonenzymatic functions. PROTACs have been proven to show better selectivity compared to classic inhibitors. PROTACs can be described as a chemical knockdown approach with rapidity and reversibility, which presents new and different biology compared to other gene editing tools by avoiding misinterpretations that arise from potential genetic compensation and/or spontaneous mutations. PRTOACs have been widely explored throughout the world and have outperformed not only in cancer diseases, but also in immune disorders, viral infections and neurodegenerative diseases. Although PROTACs present a very promising and powerful approach for crossing the hurdles of present drug discovery and tool development in biology, more efforts are needed to gain to get deeper insight into the efficacy and safety of PROTACs in the clinic. More target binders and more E3 ligases applicable for developing PROTACs are waiting for exploration.
Designing a multi-epitopic vaccine against the enterotoxigenic Bacteroides fragilis based on immunoinformatics approach
Authors: Majid Mahnoor , Andleeb Saadia
Published: December 2019

Enterotoxigenic Bacteroides fragilis is an enteric pathogen which is described as a causative agent of various intestinal infections and inflammatory diseases. Moreover, various research studies have reported it to be a leading factor in the development of colorectal cancer. As a part of the normal human microbiome, its treatment has become quite a challenge due to the alarming resistance against the available antibiotics. Although, this particular strain of B. fragilis shows susceptibility to few antibiotics, it is pertinent to devise an effective vaccine strategy for its elimination. There is no vaccine available against this pathogen up to date; therefore, we systematically ventured the outer membrane toxin producing proteins found exclusively in the toxigenic B. fragilis through the in-silico approaches to predict a multi-epitopic chimeric vaccine construct. The designed protein constitutes of epitopes which are predicted for linear B cells, Helper and T cells of outer membrane proteins expected to be putative vaccine candidates. The finalized proteins are only expressed in the enterotoxigenic B. fragilis, thus proving them to be exclusive. The 3D structure of the protein was first predicted followed by its refinement and validation via utilizing the bioinformatic approaches. Docking of the designed protein with the TLR2 receptor forecasted apt binding. Upon immune simulation, notable levels were observed in the expression of the immune cells.
Author Correction: Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial Identities in Post-Mitotic Cells
Authors: Montaner Aneley , da Silva Santana Themis Taynah , Schroeder Timm , Einicker-Lamas Marcelo , Girardini Javier , Costa Marcos Romualdo , Banchio Claudia
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: The evolutionary consequences for seawater performance and its hormonal control when anadromous Atlantic salmon become landlocked
Authors: McCormick Stephen D. , Regish Amy M. , Ardren William R. , Björnsson Björn Thrandur , Bernier Nicholas J.
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Epoxy toughening through high pressure and shear rate preprocessing
Authors: Zapico G. Fernández , Ohtake Naoto , Akasaka Hiroki , Munoz-Guijosa J. M.
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Altered visual feedback from an embodied avatar unconsciously influences movement amplitude and muscle activity
Authors: Bourdin Pierre , Martini Matteo , Sanchez-Vives Maria V.
Published: December 2019

Evidence suggests that the sense of the position of our body parts can be surreptitiously deceived, for instance through illusory visual inputs. However, whether altered visual feedback during limb movement can induce substantial unconscious motor and muscular adjustments is not known. To address this question, we covertly manipulated virtual body movements in immersive virtual reality. Participants were instructed to flex their elbow to 90° while tensing an elastic band, as their virtual arm reproduced the same, a reduced (75°), or an amplified (105°) movement. We recorded muscle activity using electromyography, and assessed body ownership, agency and proprioception of the arm. Our results not only show that participants compensated for the avatar’s manipulated arm movement while being completely unaware of it, but also that it is possible to induce unconscious motor adaptations requiring significant changes in muscular activity. Altered visual feedback through body ownership illusions can influence motor performance in a process that bypasses awareness.
Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma
Authors: Cervenkova Lenka , Vycital Ondrej , Bruha Jan , Rosendorf Jachym , Palek Richard , Liska Vaclav , Daum Ondrej , Mohelnikova-Duchonova Beatrice , Soucek Pavel
Published: December 2019

ATP-binding cassette (ABC) and solute carrier (SLC) transporters translocate diverse substances across cellular membranes and their deregulation may cause drug resistance of cancers. This study investigated significance of protein expression and cellular localization of the previously suggested putative prognostic markers ABCC2 and SLC22A3 in pancreatic cancer patients. Protein localization and brush border staining intensity of ABCC2 and SLC22A3 was assessed in tumor tissue blocks of 65 pancreatic cancer patients and associated with clinical data and survival of patients with regard to therapy. Negative SLC22A3 brush border staining in pancreatic tumors significantly increased the risk of both disease progression and patient´s death in univariate analyses. Multivariate analyses confirmed the association of SLC22A3 expression with progression-free survival of patients. A subgroup analysis of patients treated with regimens based on nucleoside analogs suggested that patients with negative brush border staining or apical localization of SLC22A3 in tumor cells have worse overall survival. The combination of positive ABCC2 and negative SLC22A3 brush border staining predicted worst overall survival and patients with positive brush border staining of both proteins had best overall and progression-free survival. The present study shows for the first time that the protein presence and to some extent also localization of SLC22A3 significantly associate with prognosis of pancreatic cancer in both unstratified and chemotherapy-treated patients. The combination of ABCC2 and SLC22A3 brush border staining also needs further attention in this regard.
Mitragynine, an euphoric compound inhibits hERG1a/1b channel current and upregulates the complexation of hERG1a-Hsp90 in HEK293-hERG1a/1b cells
Authors: Tay Yea Lu , Amanah Azimah , Adenan Mohd Ilham , Wahab Habibah Abdul , Tan Mei Lan
Published: December 2019

Mitragyna speciosa Korth (M. speciosa) has been widely used as a recreational product, however, there are growing concerns on the abuse potentials and toxicity of the plant. Several poisoning and fatal cases involving kratom and mitragynine have been reported but the underlying causes remain unclear. The human ether-a-go-go-related gene 1 (hERG1) encodes the pore-forming subunit underlying cardiac rapidly delayed rectifier potassium current (IKr). Pharmacological blockade of the IKr can cause acquired long QT syndrome, leading to lethal cardiac arrhythmias. This study aims to elucidate the mechanisms of mitragynine-induced inhibition on hERG1a/1b current. Electrophysiology experiments were carried out using Port-a-Patch system. Quantitative RT-PCR, Western blot analysis, immunofluorescence and co-immunoprecipitation methods were used to determine the effects of mitragynine on hERG1a/1b expression and hERG1-cytosolic chaperones interaction. Mitragynine was found to inhibit the IKr current with an IC50 value of 332.70 nM. It causes a significant reduction of the fully-glycosylated (fg) hERG1a protein expression but upregulates both core-glycosylated (cg) expression and hERG1a-Hsp90 complexes, suggesting possible impaired hERG1a trafficking. In conclusion, mitragynine inhibits hERG1a/1b current through direct channel blockade at lower concentration, but at higher concentration, it upregulates the complexation of hERG1a-Hsp90 which may be inhibitory towards channel trafficking.
Normal red blood cells’ shape stabilized by membrane’s in-plane ordering
Authors: Mesarec L. , Góźdź W. , Iglič A. , Kralj-Iglič V. , Virga E. G. , Kralj S.
Published: December 2019

Red blood cells (RBCs) are present in almost all vertebrates and their main function is to transport oxygen to the body tissues. RBCs’ shape plays a significant role in their functionality. In almost all mammals in normal conditions, RBCs adopt a disk-like (discocyte) shape, which optimizes their flow properties in vessels and capillaries. Experimentally measured values of the reduced volume (v) of stable discocyte shapes range in a relatively broad window between v ~ 0.58 and 0.8. However, these observations are not supported by existing theoretical membrane-shape models, which predict that discocytic RBC shape is stable only in a very narrow interval of v values, ranging between v ~ 0.59 and 0.65. In this study, we demonstrate that this interval is broadened if a membrane’s in-plane ordering is taken into account. We model RBC structures by using a hybrid Helfrich-Landau mesoscopic approach. We show that an extrinsic (deviatoric) curvature free energy term stabilizes the RBC discocyte shapes. In particular, we show on symmetry grounds that the role of extrinsic curvature is anomalously increased just below the nematic in-plane order-disorder phase transition temperature.
Developmental exposure to a mixture of perfluoroalkyl acids (PFAAs) affects the thyroid hormone system and the bursa of Fabricius in the chicken
Authors: Mattsson Anna , Sjöberg Sofia , Kärrman Anna , Brunström Björn
Published: December 2019

Perfluoroalkyl acids (PFAAs) are ubiquitous environmental contaminants and eggs and nestlings of raptors and fish-eating birds often contain high levels of PFAAs. We studied developmental effects of a mixture of ten PFAAs by exposing chicken embryos to 0.5 or 3 μg/g egg of each compound in the mixture. Histological changes of the thyroid gland were noted at both doses and increased expression of mRNA coding for type III deiodinase was found at 0.5 μg/g egg. Serum concentrations of the free fraction of thyroid hormones (T3 and T4) were reduced by the PFAA mixture at 3 µg/g egg, which is in line with a decreased synthesis and increased turnover of thyroid hormones as indicated by our histological findings and the decreased mRNA expression of type III deiodinase. The relative weight of the bursa of Fabricius increased at a dose of 3 μg/g egg in females. The bursa is the site of B-cell development in birds and is crucial for the avian adaptive immune system. Analysis of plasma and liver concentrations of the mixture components showed differences depending on chain length and functional group. Our results highlight the vulnerability of the thyroid hormone and immune systems to PFAAs.
Laser-Driven Modulation of Electron Beams in a Dielectric Micro-Structure for X-Ray Free-Electron Lasers
Authors: Hermann Benedikt , Bettoni Simona , Egenolf Thilo , Niedermayer Uwe , Prat Eduard , Ischebeck Rasmus
Published: December 2019

We describe an application of laser-driven modulation in a dielectric micro-structure for the electron beam in a free-electron laser (FEL). The energy modulation is transferred into longitudinal bunching via compression in a magnetic chicane before entering the undulator section of the FEL. The bunched electron beam comprises a series of enhanced current spikes separated by the wavelength of the modulating laser. For beam parameters of SwissFEL at a total bunch charge of 30 pC, the individual spikes are expected to be as short as 140 as (FWHM) with peak currents exceeding 4 kA. The proposed modulation scheme requires the electron beam to be focused into the micrometer scale aperture of the dielectric structure, which imposes strict emittance and charge limitations, but, due to the small interaction region, the scheme is expected to require ten times less laser power as compared to laser modulation in a wiggler magnet, which is the conventional approach to create a pulse train in FELs.
Random nanohole arrays and its application to crystalline Si thin foils produced by proton induced exfoliation for solar cells
Authors: Lee Hyeon-Seung , Choi Jae Myeong , Jung Beomsic , Kim Joonkon , Song Jonghan , Jeong Doo Seok , Park Jong-Keuk , Kim Won Mok , Lee Doh-Kwon , Lee Taek Sung , Lee Wook Seong , Lee Kyeong-Seok , Ju Byeong-Kwon , Kim Inho
Published: December 2019

We report high efficiency cell processing technologies for the ultra-thin Si solar cells based on crystalline Si thin foils (below a 50 µm thickness) produced by the proton implant exfoliation (PIE) technique. Shallow textures of submicrometer scale is essential for effective light trapping in crystalline Si thin foil based solar cells. In this study, we report the fabrication process of random Si nanohole arrays of ellipsoids by a facile way using low melting point metal nanoparticles of indium which were vacuum-deposited and dewetted spontaneously at room temperature. Combination of dry and wet etch processes with indium nanoparticles as etch masks enables the fabrication of random Si nanohole arrays of an ellipsoidal shape. The optimized etching processes led to effective light trapping nanostructures comparable to conventional micro-pyramids. We also developed the laser fired contact (LFC) process especially suitable for crystalline Si thin foil based PERC solar cells. The laser processing parameters were optimized to obtain a shallow LFC contact in conjunction with a low contact resistance. Lastly, we applied the random Si nanohole arrays and the LFC process to the crystalline Si thin foils (a 48 µm thickness) produced by the PIE technique and achieved the best efficiency of 17.1% while the planar PERC solar cell without the Si nanohole arrays exhibit 15.6%. Also, we demonstrate the ultra-thin wafer is bendable to have a 16 mm critical bending radius.
No metagenomic evidence of tumorigenic viruses in cancers from a selected cohort of immunosuppressed subjects
Authors: Passaro Nunzia , Casagrande Andrea , Chiara Matteo , Fosso Bruno , Manzari Caterina , D’Erchia Anna Maria , Iesari Samuele , Pisani Francesco , Famulari Antonio , Tulissi Patrizia , Mastrosimone Stefania , Maresca Maria Cristina , Mercante Giuseppe , Spriano Giuseppe , Corrado Giacomo , Vizza Enrico , Garbuglia Anna Rosa , Capobianchi Maria Rosaria , Mottini Carla , Cenci Alessandra , Tartaglia Marco , Costa Alessandro Nanni , Pesole Graziano , Crescenzi Marco
Published: December 2019

The possible existence of yet undiscovered human tumorigenic viruses is still under scrutiny. The development of large-scale sequencing technologies, coupled with bioinformatics techniques for the characterization of metagenomic sequences, have provided an invaluable tool for the detection of unknown, infectious, tumorigenic agents, as demonstrated by several recent studies. However, discoveries of novel viruses possibly associated with tumorigenesis are scarce at best. Here, we apply a rigorous bioinformatics workflow to investigate in depth tumor metagenomes from a small but carefully selected cohort of immunosuppressed patients. While a variegated bacterial microbiome was associated with each tumor, no evidence of the presence of putative oncoviruses was found. These results are consistent with the major findings of several recent papers and suggest that new human tumorigenic viruses are not common even in immunosuppressed populations.
Collagen fragments quantified in serum as measures of desmoplasia associate with survival outcome in patients with advanced pancreatic cancer
Authors: Willumsen Nicholas , Ali Suhail M. , Leitzel Kim , Drabick Joseph J. , Yee Nelson , Polimera Hyma V. , Nagabhairu Vinod , Krecko Laura , Ali Ayesha , Maddukuri Ashok , Moku Prashanth , Ali Aamnah , Poulose Joyson , Menon Harry , Pancholy Neha , Costa Luis , Karsdal Morten A. , Lipton Allan
Published: December 2019

Pancreatic ductal adenocarcinoma (PDAC) patients have poor prognosis and poor response to treatment. This is largely due to PDAC being associated with a dense and active stroma and tumor fibrosis (desmoplasia). Desmoplasia is characterized by excessive degradation and formation of the extracellular matrix (ECM) generating collagen fragments that are released into circulation. We evaluated the association of specific collagen fragments measured in pre-treatment serum with outcome in patients with PDAC. Matrix metalloprotease (MMP)-degraded type I collagen (C1M), type III collagen (C3M), type IV collagen (C4M) and a pro-peptide of type III collagen (PRO-C3) were measured by ELISA in pre-treatment serum from a randomized phase 3 clinical trial of patients with stage III/IV PDAC treated with 5-fluorouracil based therapy (n = 176). The collagen fragments were evaluated for their correlation (r, Spearman) with serum CA19-9 and for their association with overall survival (OS) based on Cox-regression analyses. In this phase 3 PDAC trial, pre-treatment serum collagen fragment levels were above the reference range for 67%-98% of patients, with median values in PDAC approximately two-fold higher than reference levels. Collagen fragment levels did not correlate with CA19-9 (r = 0.049–0.141,p = ns). On a continuous basis, higher levels of all collagen fragments were associated with significantly shorter OS. When evaluating degradation (C3M) and formation (PRO-C3) of type III collagen further, higher PRO-C3 was associated with poor OS (>25thpercentile cut-point, HR = 2.01, 95%CI = 1.33–3.05) and higher C3M/PRO-C3 ratio was associated with improved OS (>25thpercentile cut-point, HR = 0.53, 95%CI = 0.34–0.80). When adjusting for CA19–9 and clinical covariates, PRO-C3 remained significant (HR = 1.65, 95%CI = 1.09–2.48). In conclusion, collagen remodeling quantified in pre-treatment serum as a surrogate measure of desmoplasia was significantly associated with OS in a phase 3 clinical PDAC trial, supporting the link between desmoplasia, tumorigenesis, and response to treatment. If validated, these biomarkers may have prognostic and/or predictive potential in future PDAC trials.
MicroRNA-548 regulates high mobility group box 1 expression in patients with preterm birth and chorioamnionitis
Authors: Son Ga-Hyun , Kim Youngmi , Lee Jae Jun , Lee Keun-Young , Ham Heejin , Song Ji-Eun , Park Sung Taek , Kim Young-Han
Published: December 2019

High mobility group box 1 (HMGB1) is a prototypic alarmin and plays an important role in the pathogenesis of inflammatory process in spontaneous preterm birth. This study was conducted to compare the levels of HMGB1 in amniotic fluid and amnion membranes in women with chorioamnionitis/intra-amniotic inflammation to the levels in healthy controls. We also aimed to elucidate the involvement of microRNA-548 (miR-548) in regulating HMGB1 expression and its function in human amniotic epithelial cells (hAECs). A bioinformatics analysis predicted the binding of HMGB1 by the miR-548 cluster. A repressed and forced expression assay in hAECs was performed to investigate the causal relationship between the miR-548 cluster and HMGB1. The levels of HMGB1 in amniotic fluid and amnion membranes were significantly higher in patients with intra-amniotic inflammation/chorioamnionitis than in those without inflammation. The miR-548 was significantly under-expressed in amnion membranes from patients with chorioamnionitis than in normal term controls. Repressed expression of miR-548 up-regulated HMGB1 expression in hAECs and increased its release from hAECs. Moreover, forced expression of miR-548 suppressed HMGB1 and inflammatory cytokines in hAECs, which increased when treated with lipopolysaccharide. These results suggest miR-548 can alter the inflammatory responses in hAECs, and might be involved in the pathogenesis of preterm birth by regulating HMGB1.
Crystal structure, Hirshfeld surface analysis and DFT studies of 5-(adamantan-1-yl)-3-[(4-chlorobenzyl)sulfanyl]-4-methyl-4H-1,2,4-triazole, a potential 11β-HSD1 inhibitor
Authors: Al-Wahaibi Lamya H. , Joubert Jacques , Blacque Olivier , Al-Shaalan Nora H. , El-Emam Ali A.
Published: December 2019

5-(Adamantan-1-yl)-3-[(4-chlorobenzyl)sulfanyl]-4-methyl-4H-1,2,4-triazole (4) was identified as a potential 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor and this paper describes the in-depth structural analysis thereof. Compound 4 was synthesized in a 92% yield and its 3D-structure confirmed by single-crystal X-ray diffraction. Hirshfeld surface analysis indicated that H…H, C-H…C, C-H…Cl and especially C-H…N hydrogen bond interactions are the primary contributors to the intermolecular stabilisation in the crystal. In order to explore the properties of 4, free from the influence of the crystal field, density functional theory (DFT) calculations were conducted. Results indicated that the DFT optimized geometry of 4 produced a conformer (4a) that is significantly different from the crystal structure. Further experiments confirmed that the crystal structure is not the absolute minimum conformation. This indicated that the crystal packing forces has significantly influenced the conformation thereof. Frontier molecular orbital energies and net atomic charges were also calculated to elucidate the electronic properties of 4a. These results provided insight into areas of the molecule that may present with the ability to form binding interactions at the 11β-HSD1 active site. Molecular docking experiments revealed important intermolecular interactions between 4a and 11β-HSD1. These results indicate that 4 may be considered for further drug design endeavors.
Automated Quantification of Macular Ellipsoid Zone Intensity in Glaucoma Patients: the Method and its Comparison with Manual Quantification
Authors: Ha Ahnul , Sun Sukkyu , Kim Young Kook , Jeoung Jin Wook , Kim Hee Chan , Park Ki Ho
Published: December 2019

The macular ellipsoid zone intensity (mEZi) is a known marker of disease severity in a number of diverse ocular diseases. The purpose of this study was to establish an automated method (AM) for mEZi quantification and to compare the method’s performance with that of a manual method (MM) for glaucoma patients and healthy controls. Seventy-one (71) mild-to-moderate glaucoma patients, 71 severe-glaucoma patients, and 51 controls were enrolled. Both calibration (n = 160) and validation (n = 33) image sets were compiled. The correlation of AM to MM quantification was assessed by Deming regression for the calibration set, and a compensation formula was generated. Then, for each image in the validation set, the compensated AM quantification was compared with the mean of five repetitive MM quantifications. The AM quantification of the calibration set was found to be linearly correlated with MM in the normal-to-severe-stage glaucoma patients (R2 = 0.914). The validation set’s compensated AM quantification produced R2 = 0.991, and the relationship between the 2 quantifications was AM = 1.004(MM) + 0.139. In the validation set, the compensated AM quantification fell within MM quantification’s 95% confidence interval in 96.9% of the images. An AM for mEZi quantification was calibrated and validated relative to MM quantification for both glaucoma patients and healthy controls.
Kynurenine, 3-OH-kynurenine, and anthranilate are nutrient metabolites that alter H3K4 trimethylation and H2AS40 O-GlcNAcylation at hypothalamus-related loci
Authors: Hayakawa Koji , Nishitani Kenta , Tanaka Satoshi
Published: December 2019

Epigenetic mechanisms can establish and maintain mitotically stable patterns of gene expression while retaining the DNA sequence. These mechanisms can be affected by environmental factors such as nutrients. The importance of intracellular dosages of nutrient metabolites such as acetyl coenzyme A and S-adenosylmethionine, which are utilized as donors for post-translational modifications, is well-known in epigenetic regulation; however, the significance of indirect metabolites in epigenetic regulation is not clear. In this study, we screened for metabolites that function as epigenetic modulators. Because the expression of genes related to hypothalamic function is reportedly affected by nutritional conditions, we used a neural cell culture system and evaluated hypothalamic-linked loci. We supplemented the culture medium with 129 metabolites separately during induction of human-iPS-derived neural cells and used high-throughput ChIP-qPCR to determine the epigenetic status at 37 hypothalamus-linked loci. We found three metabolites (kynurenine, 3-OH-kynurenine, and anthranilate) from tryptophan pathways that increased H3K4 trimethylation and H2AS40 O-GlcNAcylation, resulting in upregulated gene expression at most loci, except those encoding pan-neural markers. Dietary supplementation of these three metabolites and the resulting epigenetic modification were important for stability in gene expression. In conclusion, our findings provide a better understanding of how nutrients play a role in epigenetic mechanisms.
Incorporation of dynamic segmented neutrophil-to-monocyte ratio with leukocyte count for sepsis risk stratification
Authors: Fang Wen-Feng , Chen Yu-Mu , Wang Yi-Hsi , Huang Chi-Han , Hung Kai-Yin , Fang Ying-Tang , Chang Ya-Chun , Lin Chiung-Yu , Chang Ya-Ting , Chen Hung-Cheng , Huang Kuo-Tung , Chen Yun-Che , Wang Chin-Chou , Lin Meng-Chih
Published: December 2019

The association between sepsis and segmented neutrophil-to-monocyte (SeMo) ratio is unclear. We postulated that an increase in dynamic SeMo ratio measurement can be applied in risk stratification. This retrospective study included 727 consecutive sepsis patients in medical intensive care units (ICUs), including a subpopulation of 153 patients. According to the leukocyte (white blood cell, WBC) count on day 3 (normal range, between 4,000/µL and 12,000/µL) and delta SeMo (value of SeMo ratio on day 3 minus value of SeMo ratio on day 1; normal delta SeMo, <7), patients were grouped into 3 (delta SeMo & WBC tool). The survival lines separated significantly with hazard ratios of 1.854 (1.342–2.560) for the delta SeMo or WBC abnormal group and 2.860 (1.849–4.439) for the delta SeMo and WBC abnormal group compared to the delta SeMo and WBC normal group. Delta SeMo & WBC tool and delta sequential organ failure assessment (SOFA) tool performed better than the other tools (delta SeMo, delta WBC, day 3 WBC, and day 1 WBC). Severity in delta SeMo & WBC tool and delta SeMo tool reflected the immune dysfunction score, cytokine expression, and human leukocyte antigen D-related monocyte expression on day 1 and day 3. There was correspondence between delta SOFA and delta WBC and between delta SeMo and delta cytokine expression. Incorporation of dynamic SeMo ratio with WBC count provides risk stratification for sepsis patients admitted in the ICU.
Bulk and interfacial properties of decane in the presence of carbon dioxide, methane, and their mixture
Authors: Choudhary Nilesh , Narayanan Nair Arun Kumar , Che Ruslan Mohd Fuad Anwari , Sun Shuyu
Published: December 2019

Molecular dynamics simulations were performed to study the bulk and interfacial properties of methane + n-decane, carbon dioxide + n-decane, and methane + carbon dioxide + n-decane systems under geological conditions. In addition, theoretical calculations using the predictive Peng-Robinson equation of state and density gradient theory are carried out to compare with the simulation data. A key finding is the preferential dissolution in the decane-rich phase and adsorption at the interface for carbon dioxide from the methane/carbon dioxide mixture. In general, both the gas solubility and the swelling factor increase with increasing pressure and decreasing temperature. Interestingly, the methane solubility and the swelling of the methane + n-decane system are not strongly influenced by temperature. Our results also show that the presence of methane increases the interfacial tension (IFT) of the carbon dioxide + n-decane system. Typically, the IFT of the studied systems decreases with increasing pressure and temperature. The relatively higher surface excess of the carbon dioxide + n-decane system results in a steeper decrease in its IFT as a function of pressure. Such systematic investigations may help to understand the behavior of the carbon dioxide-oil system in the presence of impurities such as methane for the design and operation of carbon capture and storage and enhanced oil recovery processes.
Risk factors associated with progressive nerve fiber layer thinning in open-angle glaucoma with mean intraocular pressure below 15 mmHg
Authors: Lee Jihei Sara , Seong Gong Je , Kim Chan Yun , Lee Sang Yeop , Bae Hyoung Won
Published: December 2019

The purpose of this study was to identify risk factors associated with progressive retinal nerve fiber layer(RNFL) thinning of open-angle glaucoma(OAG) in patients whose intraocular pressure(IOP) was maintained low with medical treatment. Based on a retrospective review of medical records, OAG patients with ≥60 months of follow-up and mean IOP below 15 mmHg were recruited. All eyes underwent IOP measurement with Goldmann applanation tonometer(GAT), standard automated perimetry(SAP), and cirrus optical coherence tomography(cirrus OCT) at 6 month or 1 year intervals. RNFL thinning was assessed using the Guided Progression Analysis(GPA) software. Forty-one eyes of 41 patients (mean age 54.9 ± 13.5) were followed up for 77.8 ± 7.8 months. GPA detected 20 eyes (48.8%) with progressive RNFL thinning(−1.5 ± 0.5 um/year), who were subsequently classified as the ‘rapid progression group.’ Those whose rate of change in RNFL thickness was slower than −1.00 µm/year was classified as the ‘slow progression group’ (n = 21, −0.0 ± 0.4 um/year, P < 0.001). Mean IOP after initiating therapy was 13.2 ± 1.1 mmHg in the rapid progression group and 13.1 ± 1.3 mmHg in the slow progression group (P = 0.300; 14.8 ± 10.0% vs. 19.6 ± 12.4% reduction, P = 0.155). Disc hemorrhage was found to more frequently occur in the rapid progression group (P = 0.001). Multivariate logistic regression analysis showed that patients with disc hemorrhage were at a higher risk for progressive RNFL thinning in OAG (OR 37.529 95% CI 2.915–483.140) after adjusting for baseline co-variates (P = 0.005). In conclusion, disc hemorrhage is associated with progressive RNFL thinning in OAG with well-maintained IOP. Factors other than IOP appear to also play a role in OAG progression.
3D Diatom–Designed and Selective Laser Melting (SLM) Manufactured Metallic Structures
Authors: Zglobicka Izabela , Chmielewska Agnieszka , Topal Emre , Kutukova Kristina , Gluch Jürgen , Krüger Peter , Kilroy Cathy , Swieszkowski Wojciech , Kurzydlowski Krzysztof J. , Zschech Ehrenfried
Published: December 2019

Diatom frustules, with their diverse three-dimensional regular silica structures and nano- to micrometer dimensions, represent perfect model systems for biomimetic fabrication of materials and devices. The structure of a frustule of the diatom Didymosphenia geminata was nondestructively visualized using nano X-ray computed tomography (XCT) and transferred into a CAD file for the first time. Subsequently, this CAD file was used as the input for an engineered object, which was manufactured by applying an additive manufacturing technique (3D Selective Laser Melting, SLM) and using titanium powder. The self-similarity of the natural and the engineered objects was verified using nano and micro XCT. The biomimetic approach described in this paper is a proof-of-concept for future developments in the scaling-up of manufacturing based on special properties of microorganisms.
Up-regulation of bone morphogenetic protein and its signaling molecules following castration of bulls and their association with intramuscular fat content in Korean cattle
Authors: Jung Da Jin Sol , Baik Myunggi
Published: December 2019

We evaluated whether castration affects bone morphogenetic protein 2 (BMP2) level and the expression of its signaling molecules in Korean cattle bulls. We also checked whether castration affects the expression of muscle fiber type and oxidative and glycolytic enzyme genes. Enzyme-linked immunosorbent assays revealed that steers had higher plasma BMP2 and leptin concentrations than bulls. Quantitative real-time PCR showed that steers had higher mRNA levels of the lysyl oxidase gene, a downstream target of the BMP signaling pathway, in the longissimus thoracis (LT) muscle. Steers had higher adipogenic peroxisome proliferator-activated receptor gamma and lipogenic fatty acid binding protein 4 mRNA levels in the LT than bulls. Steers had lower mRNA levels for several muscle fiber type 1 genes and fiber type 2A myosin heavy chain 2 gene than bulls. Steers had higher mRNA levels of the glycolytic enzyme phosphoglycerate kinase 1 gene than bulls. Transcript levels of oxidative enzyme genes did not differ between bulls and steers. Regression analysis revealed a positive association between plasma BMP2 levels and intramuscular fat (IMF) content in the steer group. These findings suggest that upregulation of the BMP signaling pathway in response to castration induces increased adipogenic gene expression, contributing to the increased IMF deposition observed in castrated animals.
Short-term rainfall forecast model based on the improved BP–NN algorithm
Authors: Liu Yang , Zhao Qingzhi , Yao Wanqiang , Ma Xiongwei , Yao Yibin , Liu Lilong
Published: December 2019

The existing methods have been used the Zenith Total Delay (ZTD) or Precipitable Water Vapor (PWV) derived from Global Navigation Satellite System (GNSS) for rainfall forecasting. However, the occurrence of rainfall is highly related to a myriad of atmospheric parameters, and a good forecast result cannot be obtained if it only depends on a single predictor. This study focused on rainfall forecasting by using a number of atmospheric parameters (such as: temperature, relative humidity, dew temperature, pressure, and PWV) based on the improved Back Propagation Neural Network (BP–NN) algorithm. Results of correlation analysis showed that each meteorological parameter contributed to rainfall. Therefore, a short-term rainfall forecast model was proposed based on an improved BP–NN algorithm by using multiple meteorological parameters. Two GNSS stations and collocated weather stations in Singapore were used to validate the proposed rainfall forecast model by using three years of data (2010–2012). True forecast (TFR), false forecast (FFR), and missed forecast (MFR) rate were introduced as evaluation indices. The experimental result revealed that the proposed model exhibited good performance with TFR larger than 96% and FFR of approximately 40%. The proposed method improved TFR by approximately 10%, whereas FFR was comparable to existing literature. This forecasted result further verified the reliability and practicability of the proposed rainfall forecasting method by using the improved BP–NN algorithm.
Controlling the selective synthesis of [2]- and [3]rotaxanes by intermolecular steric hindrance between the macrocyclic hosts
Authors: Ye Zecong , Wang Jian , Kothapalli Sudarshana Santhosh Kumar , Yang Zhiyao , Chen Lixi , Xu Weitao , Cai Yimin , Zhang Tinghui , Xiao Xin , Deng Pengchi , Feng Wen , Yuan Lihua
Published: December 2019

Selective synthesis of [2]- and [3]rotaxanes is realized using two macrocycles with little disparity of side chains in steric hindrance.
Adenosine triphosphate responsive metal–organic frameworks equipped with a DNA structure lock for construction of a ratiometric SERS biosensor
Authors: Wu Caijun , Wang Shufan , Luo Xiliang , Yuan Ruo , Yang Xia
Published: December 2019

DNA structure functionalized MOFs for construction of a ratiometric SERS biosensor to sensitively detect ATP.
Photothermal therapy-induced immunogenic cell death based on natural melanin nanoparticles against breast cancer
Authors: Li Yanhua , Liu Xiaohan , Pan Wei , Li Na , Tang Bo
Published: December 2019

A photothermal and immune co-therapy strategy based on natural melanin nanoparticles was developed for treating primary and abscopal breast cancers.
A potentiometric resolved photoelectrochemical system based on CdS nanowires and SnNb2O6nanosheets: a case application for dual biomarker analysis
Authors: Cao Jun-Tao , Ma Yan , Lv Jing-Lu , Ren Shu-Wei , Liu Yan-Ming
Published: December 2019

A potentiometric-resolved PEC immunosensor was developed for dual-target detection.
The synthesis of bayberry-like mesoporous TiO2 microspheres by a kinetics-controlled method and their hydrophilic films
Authors: Li Li , Wang Liang , Chen Xinhong , Tao Changyuan , Du Jun , Liua Zuohua
Published: December 2019

Bayberry-like mesoporous TiO2 hydrophilic films with high surface roughness and high density of surface hydroxyl groups.
3D texturing of the air–water interface by biomimetic self-assembly
Authors: Bergendal Erik , Campbell Richard A. , Pilkington Georgia A. , Müller-Buschbaum Peter , Rutland Mark W.
Published: December 2019

The air–water interface can be textured according to the same self-assembly packing criteria that determine the wealth of 3D structures found in micellar and other amphiphilic meso-phases.
Recent development and prospects of surface modification and biomedical applications of MXenes
Authors: Huang Hongye , Jiang Ruming , Feng Yulin , Ouyang Hui , Zhou Naigen , Zhang Xiaoyong , Wei Yen
Published: December 2019

MXenes, as a novel kind of two-dimensional (2D) materials, were first discovered by Gogotsi et al. in 2011.
An autonomously healable, highly stretchable and cyclically compressible, wearable hydrogel as a multimodal sensor
Authors: Tie Jianfei , Rong Liduo , Liu Hongchen , Wang Bijia , Mao Zhiping , Zhang Linping , Zhong Yi , Feng Xueling , Sui Xiaofeng , Xu Hong
Published: December 2019

Fe3+/PVAA-PAM hydrogels show highly stretchable, self-healing properties and can be used as artificial ionic skin for directly monitoring human motion.
Correction: Ordered mesoporous carbon and its applications for electrochemical energy storage and conversion
Authors: Eftekhari Ali , Fan Zhaoyang
Published: December 2019

Correction for ‘Ordered mesoporous carbon and its applications for electrochemical energy storage and conversion’ by Ali Eftekhari and Zhaoyang Fan, Mater. Chem. Front., 2017, 1, 1001–1027.
Evaluation of cytotoxic potential of structurally well-characterized RNA targeted ionic non-steroidal anti-inflammatory (NSAID) Cu(ii) & Zn(ii) DACH–mefenamato drug conjugates against human cancer cell lines
Authors: Khan Huzaifa Yasir , Tabassum Sartaj , Arjmand Farukh
Published: December 2019

New RNA targeted ionic NSAID drug conjugates were evaluated for their antiproliferative activity against human cancer cell lines.
Electrochemical detection of 2-nitrophenol using a heterostructure ZnO/RuO2 nanoparticle modified glassy carbon electrode
Authors: Uddin Md. Tamez , Alam Md. Mahmud , Asiri Abdullah Mohamed , Rahman Mohammed Muzibur , Toupance Thierry , Islam Md. Akhtarul
Published: December 2019

A highly selective chemisensor for 2-nitrophenol detection was fabricated using ZnO/RuO2 nanoparticles (NPs) synthesized by impregnation method.
Aggregation of biologically important peptides and proteins: inhibition or acceleration depending on protein and metal ion concentrations
Authors: Poulson Benjamin Gabriel , Szczepski Kacper , Lachowicz Joanna Izabela , Jaremko Lukasz , Emwas Abdul-Hamid , Jaremko Mariusz
Published: December 2019

The process of aggregation of proteins and peptides is dependent on the concentration of proteins, and the rate of aggregation can be altered by the presence of metal ions, but this dependence is not always a straightforward relationship.
A conjugated polyelectrolyte interfacial modifier for high performance near-infrared quantum-dot photodetectors
Authors: Jeong Moon-Ki , Kang Jinhyeon , Park Dasom , Yim Sanggyu , Jung In Hwan
Published: December 2019

The photodetection properties of near-infrared quantum-dot photodetectors (NIR-QPDs) were enhanced by introducing three kinds of novel cationic conjugated polyelectrolytes (CCPs).
Thermo-responsive shape memory sensors based on tough, remolding and anti-freezing hydrogels
Authors: Yang Tianyu , Wang Mian , Jia Fei , Ren Xiuyan , Gao Guanghui
Published: December 2019

A tough, anti-freezing, and remolding shape memory hydrogel sensor for human motion monitoring and a temperature alarm.
Hemagglutinin of Influenza A, but not of Influenza B and C viruses is acylated by ZDHHC2, 8, 15 and 20
Authors: Gadalla Mohamed Rasheed , Abrami Laurence , van der Goot F. Gisou , Veit Michael
Published: December 2019

Hemagglutinin (HA), a glycoprotein of Influenza A viruses and its proton channel M2 are site-specifically modified with fatty acids. Whereas two cysteines in the short cytoplasmic tail of HA contain only palmitate, stearate is exclusively attached to one cysteine located at the cytoplasmic border of the transmembrane region (TMR). M2 is palmitoylated at a cysteine positioned in an amphiphilic helix near the TMR. The enzymes catalyzing acylation of HA and M2 have not been identified, but zinc finger DHHC domain-containing (ZDHHC) palmitoyltransferases are candidates. We used a siRNA library to knockdown expression of each of the 23 human ZDHHCs in HA-expressing HeLa cells. siRNAs against ZDHHC2 and 8 had the strongest effect on acylation of HA as demonstrated by Acyl-RAC and confirmed by 3H-palmitate labeling. CRISPR/Cas9 knockout of ZDHHC2 and 8 in HAP1 cells, but also of the phylogenetically related ZDHHCs 15 and 20 strongly reduced acylation of group 1 and group 2 HAs and of M2, but individual ZDHHCs exhibit slightly different substrate preferences. These ZDHHCs co-localize with HA at membranes of the exocytic pathway in a human lung cell line. ZDHHC2, 8, 15 and 20 are not required for acylation of the HA-esterase-fusion protein of Influenza C virus that contains only stearate at one transmembrane cysteine. Knockout of these ZDHHCs also did not compromise acylation of HA of Influenza B virus that contains two palmitoylated cysteines in its cytoplasmic tail. Results are discussed with respect to the acyl preferences and possible substrate recognition features of the identified ZDHHCs.
Editor's cut: DNA cleavage by CRISPR RNA-guided nucleases Cas9 and Cas12a
Authors: Swartjes Thomas , Staals Raymond H.J. , van der Oost John
Published: December 2019

Discovered as an adaptive immune system of prokaryotes, CRISPR–Cas provides many promising applications. DNA-cleaving Cas enzymes like Cas9 and Cas12a, are of great interest for genome editing. The specificity of these DNA nucleases is determined by RNA guides, providing great targeting adaptability. Besides this general method of programmable DNA cleavage, these nucleases have different biochemical characteristics, that can be exploited for different applications. Although Cas nucleases are highly promising, some room for improvement remains. New developments and discoveries like base editing, prime editing, and CRISPR-associated transposons might address some of these challenges.
Adaptive boundary determination for network reduction in long‐term voltage stability analyses
Authors: Khalilifar Mahtab , Joorabian Mahmood , Seifosadat Seyed Ghodratolah , Shahrtash Seyed Mohammad
Published: December 2019

In this study, a simple, fast, and adaptive network reduction procedure is presented for long‐term voltage stability analyses, to speed up the simulation time. The proposed procedure consists of two parts including disturbance detection based on data from synchronised measurement devices; and the rest, up to the final estimated values, based on simulations and calculations. In turn, simulations and calculations result in an adaptive dynamic‐oriented determination of external sub‐network (according to the disturbance occurred) and substituting an appropriate equivalent for that subsystem. The external subsystem is determined without any need to measure post‐disturbance data, while the detection criteria are calculated by simulations at 0.8 s after disturbance occurrence. The results have shown considerable reduction in the simulation time while providing acceptable accuracy in delivering the time of voltage instability occurrences, especially when applying the proposed error compensation procedure.
Cable incipient fault identification using restricted Boltzmann machine and stacked autoencoder
Authors: Wang Ying , Lu Hong , Xiao Xianyong , Yang Xiaomei , Zhang Wenhai
Published: December 2019

Cable incipient fault is an intermittent arc fault, and may evolve into a permanent fault. Due to the short duration of the fault, the conventional overcurrent protection device cannot detect it. A cable incipient fault identification method is proposed in this study, using restricted Boltzmann machine (RBM) and stacked autoencoder (SAE). Firstly, disturbance current waveforms data is effectively compressed by RBM, which can improve analysis efficiency and obtain the shallow features of the data. Then, the compressed data is used as the input of SAE, and the optimal network parameters are obtained through layer‐by‐layer pre‐training and fine‐tuning. Finally, a well‐trained SAE network is used to learn deep features from the input data to identify cable incipient fault, and softmax outputs identification result. In addition, the performance of the proposed method is compared with other methods. The accuracy of the proposed method is 98.33/95.62% for simulated data/measured data, and is 1.66/1.09%, 3.33/1.76%, 17.31/28.48% and 40.17/46.1% higher than the accuracies of convolutional neural network, deep belief network, random forest and back propagation neural network, respectively. The results show that the proposed method has high identification accuracy and feasibility.
Defect characterisation using pulse compression‐based quadratic frequency modulated thermal wave imaging
Authors: Subhani Shaik , Chandra Sekhar Yadav Gampa V.P. , Ghali Venkata Subbarao
Published: December 2019

Quantitative depth estimation, along with enhanced defect detectability, is of utmost importance for subsurface analysis in thermal wave imaging for a variety of applications. However, the size and the depth of the subsurface anomalies influence this quantitative analysis due to the non‐consideration of back reflection from the defect boundary in addition to three‐dimensional scattering effects. This study explores an experimental validation of an analytical model for quantitative depth analysis of subsurface anomalies in thermal wave detection and ranging using quadratic frequency‐modulated stimulation with pulse compression based signal processing approach and presents the depth resolution feature by considering the back reflection at the defect boundary. It also presents a study on the influence of the size of the anomaly and bandwidth of the stimulation on quantitative depth prediction using the experimentation carried over a carbon fibre reinforced plastic and mild steel specimen with artificial flat‐bottom holes.