bluuebunny/crossref_metadata_2025 huggingface dataset:
Influences of Immunocastration on Endocrine Parameters, Growth Performance and Carcass Quality, as Well as on Boar Taint and Penile Injuries
Authors: Zoels Susanne , Reiter Simon , Ritzmann Mathias , Weiß Christine , Numberger Jasmin , Schütz Aneka , Lindner Peter , Stefanski Volker , Weiler Ulrike
Published: February 2020

Castration of male pigs without anesthesia is a significant welfare issue. Improvac®, a GnRH vaccine induces an endogenous immune response leading to a decrease in testicular steroids. Consequences of different vaccination schemes on testicular function and carcass quality were evaluated in immunocastrated boars (IC), surgical castrates (SC), and entire males (EM). Therefore, 128 male piglets were assigned to five treatment-groups and a long term follow-up group. IC groups received two vaccinations (V1, V2) with Improvac® at 8 and 12, 12 and 16, or 12 and 18 weeks. Testosterone-concentrations decreased significantly two weeks after V2 in feces and dropped in serum from V2 to slaughter (S) except IC-8/12 without differing significantly. GnRH-binding results indicated the highest values for IC-12/18 animals. While IC-12/16 and IC-12/18 animals showed boar taint compounds below the threshold levels, two IC-8/12 animals had concentrations above the threshold level. Feed-efficiency was higher in EM than in SC with IC in between. In IC compared to EM, a decreasing amount of polyunsaturated-fatty-acids was obvious and GnRH-vaccination reduced penile injuries. The examined vaccination protocols reduce penile injuries, improve feed efficiency and carcass quality, and reliably prevents boar taint, if manufacturer’s recommendations concerning vaccination schedules are applied. Therefore immunocastration offers a reliable, animal friendly alternative to surgical castration.
Modified Aminoglycosides Bind Nucleic Acids in High-Molecular-Weight Complexes
Authors: Ying Lanqing , Zhu Hongkun , Fosso Marina Y. , Garneau-Tsodikova Sylvie , Fredrick Kurt
Published: February 2020

Aminoglycosides represent a large group of antibiotics well known for their ability to target the bacterial ribosome. In studying 6”-substituted variants of the aminoglycoside tobramycin, we serendipitously found that compounds with C12 or C14 linear alkyl substituents potently inhibit reverse transcription in vitro. Initial observations suggested specific inhibition of reverse transcriptase. However, further analysis showed that these and related compounds bind nucleic acids with high affinity, forming high-molecular weight complexes. Stable complex formation is observed with DNA or RNA in single- or double-stranded form. Given the amphiphilic nature of these aminoglycoside derivatives, they likely form micelles and/or vesicles with surface-bound nucleic acids. Hence, these compounds may be useful tools to localize nucleic acids to surfaces or deliver nucleic acids to cells or organelles.
Measurement and Evaluation for Interbedded Pore Water Pressure of Saturated Asphalt Pavement under Vehicle Loading
Authors: Chen Wuxing , Wang Zhenyong , Guo Wei , Dai Wenting
Published: February 2020

Dynamic water scouring damage is the main cause of pavement structure damage, and the main reason for dynamic water scouring damage is the rapid change of pore water pressure caused by vehicle load. Numerical simulation is a commonly used pore water pressure test technology, but its accuracy is not high, and the test data are very different to actual values. In this study, a pore water pressure test method is designed, which has the advantages of less disturbance to the pavement structure and the measured data are closer to the true pore water pressure value of the pavement structure. Measurement data show that the pore water pressure gradually increases with increasing vehicle speed, and the pore water pressure response time becomes shorter. The pore water pressure response time is greater than vehicle loading time. Moreover, the phenomenon of periodic decay of pore water pressure with time is analyzed based on hydrodynamic water hammer theory. The empirical formula of maximum positive pressure with speed and the empirical formula of Abp at different speeds were obtained.
Non-Similar Solution of G-jitter Induced Unsteady Magnetohydrodynamic Radiative Slip Flow of Nanofluid
Authors: Uddin M.J. , Khan W.A. , Bég O. Anwar , Ismail A. I. M.
Published: February 2020

We present a mathematical model and numerical simulation of the unsteady 2-D g-jitter-free and forced the convective flow of water-based nanofluid from a flat plate, considering both the velocity slip and thermal slip conditions imposed on the wall of the plate. The Darcian model is used, and both cases of a calm and moving free stream are considered. In place of the extensively used linearly varying radiative heat flux, the nonlinearly varying heat flux calculation is applied to produce practically useful results. Further, we incorporate the “zero mass flux boundary condition” which is believed to be more realistic than the earlier extensively used “actively” controlled model. The parameter influences the non-dimensional velocity, temperature, nanoparticle volume fraction, skin friction and heat transfer rates are visualized graphically and discussed in detail. Special cases of the results are benchmarked with those existing in the literature, and a good arrangement is obtained. It is found that the rate of heat transfer is lower for the calm free stream rather than the moving free stream.
Hierarchical Multi-Stage Cyber Attack Scenario Modeling Based on G&E Model for Cyber Risk Simulation Analysis
Authors: Ahn Myung Kil , Kim Yong Hyun , Lee Jung-Ryun
Published: February 2020

With the advancement in cyber-defense capabilities, cyber attacks have continued to evolve like living creatures to breach security. Assuming the possibility of various enemy attacks, it is necessary to select an appropriate course of action by proactively analyzing and predicting the consequences of a particular security event. Cyber attacks, especially in large-scale military network environments, have a fatal effect on security; therefore, various experiments and analyses must be conducted to establish the necessary preparations. Herein, we propose a hierarchical multi-stage cyber attack scenario modeling based on the goal and effect (G&E) model and analysis system, which enables expression of various goals of attack and damage effects without being limited to specific type. The proposed method is applicable to large-scale networks and can be utilized in various scenario-based cyber combat experiments.
Interval Identification of Thermal Parameters Using Trigonometric Series Surrogate Model and Unbiased Estimation Method
Authors: Wang Xiaoguang , He Weiliang , Zhao Linggong
Published: February 2020

Metal-foam materials have been applied in many engineering fields in virtue of its high specific strength and desirable of thermodynamic properties. However, due to the inherent uncertainty of its attribute parameters, reliable analysis results are often ambiguous to obtain accurately. To overcome this drawback, this paper proposes a novel interval parameter identification method. Firstly, a novel modelling methodology is proposed to simulate the geometry of engineering metal foams. Subsequently, the concept of intervals is introduced to represent the uncertainty relationship between variables and responses in heat transfer systems. To improve computational efficiency, a novel augmented trigonometric series surrogate model is constructed. Moreover, unbiased estimation methods based on different probability distributions are presented to describe system measurement intervals. Then, a multi-level optimization-based identification strategy is proposed to seek the parameter interval efficiently. Eventually, an engineering heat transfer system is given to verify the feasibility of the proposed parameter identification method. This method can rapidly identify the unknown parameters of the system. The identification results demonstrate that this interval parameter identification method can quantify the uncertainty of a metal-foam structure in engineering heat transfer systems efficiently, especially for the actual case without sufficient measurements.
Characteristics of the Wind Environment above Bridge Deck near the Pylon Zone and Wind Barrier Arrangement Criteria
Authors: Wang Dalei , Zhang Yiquan , Sun Mengjin , Chen Airong
Published: February 2020

Due to the complex arrangement of structural components in the vicinity of bridge pylon zones, the wind environment above bridge decks is very complicated. A sudden change in wind speed exerts an adverse effect on vehicle control stability. In order to investigate the characteristics of the flow field in the vicinity of the bridge pylon, the wind environment near an inverted Y-shaped pylon is studied by experimental and numerical methods. From the flow visualization and the wind speed measurement in the wind tunnel and the numerical simulation created using Fluent software, specific patterns of the direction and magnitude of wind speed at a range of vehicle height above the bridge deck near the pylon zone were observed along the longitudinal direction. This distribution pattern of the wind environment can effectively guide the wind barrier arrangement near the bridge pylon zone. Combined with the two safety evaluation indicators proposed in this paper, the optimal arrangement scheme of wind barriers in the bridge pylon zone of Sutong Bridge is determined. This paper deepens the understanding of the wind environment near the pylon zone and proposes an evaluation method for the wind environment near the pylon zone, which can serve as the basis for wind barrier arrangement in similar research projects.
Parametric and Nonparametric PI Controller Tuning Method for Integrating Processes Based on Magnitude Optimum
Authors: Kos Tomaž , Huba Mikuláš , Vrančić Damir
Published: February 2020

Integrating systems are frequently encountered in the oil industry (oil–water–gas separators, distillation columns), power plants, paper-production plants, polymerisation processes, and in storage tanks. Due to the non-self-regulating character of the processes, any disturbance can cause a drift of the process output signal. Therefore, efficient closed-loop control of such processes is required. There are many PI and PID controller tuning methods for integrating processes. However, it is hard to find one requiring only a simple tuning procedure on the process, while the tuning method is based either on time-domain measurements or on a process transfer function of arbitrary order, which are the advantages of the magnitude optimum multiple integration (MOMI) tuning method. In this paper, we propose the extension of the MOMI tuning method to integrating processes. Besides the mentioned advantages, the extension provides efficient closed-loop control, while PI controller parameters calculation is still based on simple algebraic expressions, making it suitable for less-demanding hardware, like simpler programmable logic controllers (PLC). Additionally, the proposed method incorporates reference weighting factor b that allows users to emphasize either the disturbance-rejection or reference-following response. The proposed extension of the MOMI method (time-domain approach) was also tested on a charge-amplifier drift-compensation system, a laboratory hydraulic plant, on an industrial autoclave, and on a solid-oxide fuel-cell temperature control. All closed-loop responses were relatively stable and fast, all in accordance with the magnitude optimum criteria.
A Novel Self-Healing Strategy for Distribution Network with Distributed Generators Considering Uncertain Power-Quality Constraints
Authors: Ke Song , Lin Tao , Chen Rusi , Du Hui , Li Shuitian , Xu Xialing
Published: February 2020

Self-healing of smart distribution networks with distributed generators, which are usually operated as independent islands after fault, can improve power-supply reliability. As a hot research topic, a self-healing scheme is usually treated as the output of a nonlinear optimizuoation model. However, existing strategies have two main shortcomings. The first, high-optimization dimension, results in low-optimization efficiency. The second, the effects of power-quality issues, which are more serious on islands and may further threaten the safe operation of islands, is usually neglected. To quickly obtain a reliable self-healing scheme, a novel strategy is proposed. As the first step, the distribution network after a fault occurrence can be divided into several trouble-free subnets via the connectivity analysis; each subnet is called an initial island. Further, for each initial island, a two-step optimization model of self-healing, which consists of load-shedding optimization and network reconfiguration optimization, is proposed to obtain the self-healing strategy with lower searching space as well as higher solving efficiency. In detail, in load-shedding optimization, by means of heuristic differential evolution algorithm, larger total recovery capacity is achieved by considering the droop characteristic of distributed generators (DGs) within the permissible change in frequency. In network-reconfiguration optimization, based on the improved hybrid particle swarm optimization algorithm, a comprehensive set of power-quality constraints, including constraint of change in frequency, uncertain constraints of node voltage total harmonic distortion (THD), and negative sequence components of DGs, is developed to guarantee the reliability of each island. To evaluate whether the constraints are satisfied during the optimization procedure, an improved flexible power-flow algorithm is developed to calculate the power flow of each island under change in frequency. Further, 2m+1-point estimate method is employed for uncertainty analyses of the distributions of harmonic and negative sequence components caused by the uncertainty of corresponding sources. Finally, via a 94-node practical distribution network, the effectiveness and advantages of the proposed strategy in safety, recovery capacity, and optimization efficiency are verified.
Modelling a Spatial-Motion Deep Learning Framework to Classify Dynamic Patterns of Videos
Authors: Kasthuri Arachchi Sandeli Priyanwada , Shih Timothy K. , Hakim Noorkholis Luthfil
Published: February 2020

Video classification is an essential process for analyzing the pervasive semantic information of video content in computer vision. Traditional hand-crafted features are insufficient when classifying complex video information due to the similarity of visual contents with different illumination conditions. Prior studies of video classifications focused on the relationship between the standalone streams themselves. In this paper, by leveraging the effects of deep learning methodologies, we propose a two-stream neural network concept, named state-exchanging long short-term memory (SE-LSTM). With the model of spatial motion state-exchanging, the SE-LSTM can classify dynamic patterns of videos using appearance and motion features. The SE-LSTM extends the general purpose of LSTM by exchanging the information with previous cell states of both appearance and motion stream. We propose a novel two-stream model Dual-CNNSELSTM utilizing the SE-LSTM concept combined with a Convolutional Neural Network, and use various video datasets to validate the proposed architecture. The experimental results demonstrate that the performance of the proposed two-stream Dual-CNNSELSTM architecture significantly outperforms other datasets, achieving accuracies of 81.62%, 79.87%, and 69.86% with hand gestures, fireworks displays, and HMDB51 datasets, respectively. Furthermore, the overall results signify that the proposed model is most suited to static background dynamic patterns classifications.
On-Machine Precision Form Truing and In-Situ Measurement of Resin-Bonded Spherical Diamond Wheel
Authors: Wang Jinhu , Zhao Qingliang , Zhang Chunyu , Guo Bing , Yuan Julong
Published: February 2020

The resin-bonded spherical diamond wheel is widely used in arc envelope grinding, where the demands for form accuracy are high and the form truing process is challenging. In this paper, on-machine precision form truing of the resin-bonded spherical diamond wheel is accomplished by using a coarse-grained diamond roller, and in-situ measurement of the form-truing error is conducted through a laser scan micrometer. Firstly, a novel biarc curve-fitting method is proposed based on the in-situ measurement results to calculate the alignment error between the diamond roller and the spherical diamond wheel. Then, on-machine precision form truing of a D46 resin-bonded spherical diamond wheel is completed after alignment error compensation. The in-situ measurement results show that the low-frequency form-truing error is approximately 5 μm. In addition, the actual form-trued diamond wheel has been employed in grinding a test specimen, and the resulting form accuracy is approximately 1.6 μm without any compensation. The ground surface profile shared similar characteristics with the roller-trued diamond wheel profile, confirming that the diamond roller truing and in-situ measurements methods are accurate and feasible.
Ambient Air Quality in the Czech Republic: Past and Present
Authors: Hůnová Iva
Published: February 2020

Based on an analysis of related core papers and reports, this review presents a historical perspective on ambient air pollution and ambient air quality development in the modern-day Czech Republic (CR) over the past seven decades, i.e., from the 1950s to the present. It offers insights into major air pollution problems, reveals the main hot spots and problematic regions and indicates the principal air pollutants in the CR. Air pollution is not presented as a stand-alone problem, but in the wider context of air pollution impacts both on human health and the environment in the CR. The review is arranged into three main parts: (1) the time period until the Velvet Revolution of 1989, (2) the transition period of the 1990s and (3) the modern period after 2000. Obviously, a major improvement in ambient air quality has been achieved since the 1970s and 1980s, when air pollution in the former Czechoslovakia culminated. Nevertheless, new challenges including fine aerosol, benzo[a]pyrene and ground-level ozone, of which the limit values are still vastly exceeded, have emerged. Furthermore, in spite of a significant reduction in overall emissions, the atmospheric deposition of nitrogen, in particular, remains high in some regions.
Radar-Based Precipitation Climatology in Germany—Developments, Uncertainties and Potentials
Authors: Kreklow Jennifer , Tetzlaff Björn , Burkhard Benjamin , Kuhnt Gerald
Published: February 2020

Precipitation is a crucial driver for many environmental processes and weather radars are capable of providing precipitation information with high spatial and temporal resolution. However, radar-based quantitative precipitation estimates (QPE) are also subject to various potential uncertainties. This study explored the development, uncertainties and potentials of the hourly operational German radar-based and gauge-adjusted QPE called RADOLAN and its reanalyzed radar climatology dataset named RADKLIM in comparison to ground-truth rain gauge data. The precipitation datasets were statistically analyzed across various time scales ranging from annual and seasonal aggregations to hourly rainfall intensities in regard to their capability to map long-term precipitation distribution, to detect low intensity rainfall and to capture heavy rainfall. Moreover, the impacts of season, orography and distance from the radar on long-term precipitation sums were examined in order to evaluate dataset performance and to describe inherent biases. Results revealed that both radar products tend to underestimate total precipitation sums and particularly high intensity rainfall. However, our analyses also showed significant improvements throughout the RADOLAN time series as well as major advances through the climatologic reanalysis regarding the correction of typical radar artefacts, orographic and winter precipitation as well as range-dependent attenuation.
Impact of Global Warming on Extreme Heavy Rainfall in the Present Climate: Case Study of Heavy Rainfall in Kinugawa, Japan (2015)
Authors: Taniguchi Kenji , Minobe Yuto
Published: February 2020

Hazardous heavy rainfall and wide-scale inundation occurred in the Kinugawa River basin, north of Tokyo, in 2015. In this study, ensemble hindcast and non-global warming (NGW) simulations of this heavy rainfall event were implemented. In the NGW simulations, initial and boundary conditions were generated by using the outputs of natural forcing historical experiments by twelve different global climate models. The results of the hindcast and NGW simulations indicated the high likelihood of the generation of linear heavy rainfall bands and the intensification of Kinugawa heavy rainfall due to anthropogenic greenhouse gas emissions. However, in some NGW simulations, the total rainfall was greater than in the hindcast. In addition, the maximum total rainfall was greater in many NGW simulations. Lower atmospheric temperature, sea surface temperature (SST), and precipitable water content (PWC) under the initial conditions can cause less rainfall in the NGW simulations. However, some discrepancies were found in the initial conditions and simulated rainfall; less rainfall with higher atmospheric temperature, SST and PWC, and vice versa. A detailed investigation of simulated atmospheric conditions explained the simulated rainfall. These results indicate that it is not sufficient to examine climatological anomalies to understand individual extreme weather events, but that detailed simulations are useful.
Effect of Ultrasound Application on Protein Yield and Fate of Alkaloids during Lupin Alkaline Extraction Process
Authors: Aguilar-Acosta Luis , Serna-Saldivar Sergio , Rodríguez-Rodríguez José , Escalante-Aburto Anayansi , Chuck-Hernández Cristina
Published: February 2020

The objective of this work is to elucidate the fate of quinolizidine alkaloids (QA) during the lupin protein extraction process assisted with ultrasound and the evaluation of the nutritional and functional properties of the protein fraction. Proximal characterization, concentration of anti-nutritional compounds, amino acid profile and protein solubility profile of flours from three lupin species were (L. albus, L. angustifolius and L. mutabilis) assessed. The result showed a significant difference (p < 0.05) in protein concentration, fat, total alkaloids and particle size between the three species flours. Based on these parameters, the most different Lupinus species (L. mutabilis and L. angustifolius) were chosen to study the behavior of the protein fraction in terms of functionality, composition and resistance to thermal treatments. The results obtained for L. mutabilis described the ultrasound effect as beneficial for protein yield (14% more than control), QA reduction from bagasse (81% less than control) and protein isolate production (50% less than control). On the other hand, L. angustifolius was more resistant to the ultrasound effect with no significant difference between treatments (10 and 15 min) and control but with the lower toxicity and better amino acid score. These results will be useful to design processes to assist in the objective of meeting the future protein demand of the population.
2,4-Dichlorophenoxyacetic Thiosemicarbazides as a New Class of Compounds against Stomach Cancer Potentially Intercalating with DNA
Authors: Pitucha Monika , Korga-Plewko Agnieszka , Kozyra Pawel , Iwan Magdalena , Kaczor Agnieszka A.
Published: February 2020

Thiosemicarbazide is a useful structural moiety that has the biological potential. Optimization of this structure can result in groundbreaking discovery of a new class of therapeutic agents. In the light of this, 1-(2,4-dichlorophenoxy)acetyl-4-(1-naphthyl)thiosemicarbazide (1) and 1,4-bis[(2,4-dichlorophenoxy)acetylthiosemicarbazide]phenyl (2) were synthesized and characterized by spectroscopic method. Cytotoxicity of obtained compounds was evaluated on MKN74 gastric cancer cell line and human skin fibroblast BJ based on methylthiazolyldiphenyl-tetrazolium bromide (MTT) test. The apoptosis/necrosis and cell cycle analysis were conducted using image cytometry. Additionally, in DNA of treated cells, abasic sites (AP) and double strands breaks (DSB) presence were measured. Intercalating properties of active compounds were evaluated using the UV–spectroscopic method. Among newly synthesized derivatives, compound 2 showed toxic effects on gastric cancer cells with simultaneous lack of toxicity to normal fibroblasts. Cell cycle analysis revealed that both compounds influence cell division mainly at the stage of replication. Simultaneously with DNA synthesis disorders, DNA damages like AP-sites and DSBs were observed. Spectroscopic studies revealed possible DNA intercalating properties of tested compounds. Obtained results indicate that the newly synthesized thiosemicarbazide derivatives are a promising group of compounds with potential anticancer activity resulted from interactions with DNA and cell cycle interrupt.
Follow the Mutations: Toward Class-Specific, Small-Molecule Reactivation of p53
Authors: Loh Stewart N.
Published: February 2020

The mutational landscape of p53 in cancer is unusual among tumor suppressors because most of the alterations are of the missense type and localize to a single domain: the ~220 amino acid DNA-binding domain. Nearly all of these mutations produce the common effect of reducing p53’s ability to interact with DNA and activate transcription. Despite this seemingly simple phenotype, no mutant p53-targeted drugs are available to treat cancer patients. One of the main reasons for this is that the mutations exert their effects via multiple mechanisms—loss of DNA contacts, reduction in zinc-binding affinity, and lowering of thermodynamic stability—each of which involves a distinct type of physical impairment. This review discusses how this knowledge is informing current efforts to develop small molecules that repair these defects and restore function to mutant p53. Categorizing the spectrum of p53 mutations into discrete classes based on their inactivation mechanisms is the initial step toward personalized cancer therapy based on p53 allele status.
Targeting the Class A Carbapenemase GES-5 via Virtual Screening
Authors: Klein Raphael , Cendron Laura , Montanari Martina , Bellio Pierangelo , Celenza Giuseppe , Maso Lorenzo , Tondi Donatella , Brenk Ruth
Published: February 2020

The worldwide spread of β-lactamases able to hydrolyze last resort carbapenems contributes to the antibiotic resistance problem and menaces the successful antimicrobial treatment of clinically relevant pathogens. Class A carbapenemases include members of the KPC and GES families. While drugs against KPC-type carbapenemases have recently been approved, for GES-type enzymes, no inhibitors have yet been introduced in therapy. Thus, GES carbapenemases represent important drug targets. Here, we present an in silico screening against the most prevalent GES carbapenemase, GES-5, using a lead-like compound library of commercially available compounds. The most promising candidates were selected for in vitro validation in biochemical assays against recombinant GES-5 leading to four derivatives active as high micromolar competitive inhibitors. For the best inhibitors, the ability to inhibit KPC-2 was also evaluated. The discovered inhibitors constitute promising starting points for hit to lead optimization.
Regulation of Electromagnetic Perceptive Gene Using Ferromagnetic Particles for the External Control of Calcium Ion Transport
Authors: Hwang Jangsun , Choi Yonghyun , Lee Kyungwoo , Krishnan Vijai , Pelled Galit , Gilad Assaf A. , Choi Jonghoon
Published: February 2020

Developing synthetic biological devices to allow the noninvasive control of cell fate and function, in vivo can potentially revolutionize the field of regenerative medicine. To address this unmet need, we designed an artificial biological “switch” that consists of two parts: (1) the electromagnetic perceptive gene (EPG) and (2) magnetic particles. Our group has recently cloned the EPG from the Kryptopterus bicirrhis (glass catfish). The EPG gene encodes a putative membrane-associated protein that responds to electromagnetic fields (EMFs). This gene’s primary mechanism of action is to raise the intracellular calcium levels or change in flux through EMF stimulation. Here, we developed a system for the remote regulation of [Ca2+]i (i.e., intracellular calcium ion concentration) using streptavidin-coated ferromagnetic particles (FMPs) under a magnetic field. The results demonstrated that the EPG-FMPs can be used as a molecular calcium switch to express target proteins. This technology has the potential for controlled gene expression, drug delivery, and drug developments.
Fluorescein Derivatives as Antibacterial Agents Acting via Membrane Depolarization
Authors: Nazarov Pavel A. , Kirsanov Roman S. , Denisov Stepan S. , Khailova Ljudmila S. , Karakozova Marina V. , Lyamzaev Konstantin G. , Korshunova Galina A. , Lukyanov Konstantin A. , Kotova Elena A. , Antonenko Yuri N.
Published: February 2020

Appending a lipophylic alkyl chain by ester bond to fluorescein has been previously shown to convert this popular dye into an effective protonophoric uncoupler of oxidative phosphorylation in mitochondria, exhibiting neuro- and nephroprotective effects in murine models. In line with this finding, we here report data on the pronounced depolarizing effect of a series of fluorescein decyl esters on bacterial cells. The binding of the fluorescein derivatives to Bacillus subtilis cells was monitored by fluorescence microscopy and fluorescence correlation spectroscopy (FCS). FCS revealed the energy-dependent accumulation of the fluorescein esters with decyl(triphenyl)- and decyl(tri-p-tolyl)phosphonium cations in the bacterial cells. The latter compound proved to be the most potent in suppressing B. subtilis growth.
The Role of Retinoic Acid in Establishing the Early Limb Bud
Authors: Feneck Eleanor , Logan Malcolm
Published: February 2020

Retinoic acid (RA) was one of the first molecules in the modern era of experimental embryology to be shown capable of generating profound effects on limb development. In this review, we focus on the earliest events of limb development and specifically on the role of RA in establishing the domain of cells that will go on to form the limb itself. Although there is some consensus on the role of RA during the earliest stages of limb formation, some controversy remains on the mechanism of RA action and the requirement for RA signaling in forming the hindlimb buds.
Regulation of Adipsin Expression by Endoplasmic Reticulum Stress in Adipocytes
Authors: Ryu Ka-Young , Jeon Eon Ju , Leem Jaechan , Park Jae-Hyung , Cho Hochan
Published: February 2020

Adpsin is an adipokine that stimulates insulin secretion from β-cells and improves glucose tolerance. Its expression has been found to be markedly reduced in obese animals. However, it remains unclear what factors lead to downregulation of adipsin in the context of obesity. Endoplasmic reticulum (ER) stress response is activated in various tissues under obesity-related conditions and can induce transcriptional reprogramming. Therefore, we aimed to investigate the relationship between adipsin expression and ER stress in adipose tissues during obesity. We observed that obese mice exhibited decreased levels of adipsin in adipose tissues and serum and increased ER stress markers in adipose tissues compared to lean mice. We also found that ER stress suppressed adipsin expression via adipocytes-intrinsic mechanisms. Moreover, the ER stress-mediated downregulation of adipsin was at least partially attributed to decreased expression of peroxisome proliferator-activated receptor γ (PPARγ), a key transcription factor in the regulation of adipocyte function. Finally, treatment with chemical chaperones recovered the ER stress-mediated downregulation of adipsin and PPARγ in vivo and in vitro. Our findings suggest that activated ER stress in adipose tissues is an important cause of the suppression of adipsin expression in the context of obesity.
Kernel Differential Subgraph Analysis to Reveal the Key Period Affecting Glioblastoma
Authors: Xie Jiang , Sun Jiamin , Feng Jiatai , Yang Fuzhang , Wang Jiao , Wen Tieqiao , Nie Qing
Published: February 2020

Glioblastoma (GBM) is a fast-growing type of malignant primary brain tumor. To explore the mechanisms in GBM, complex biological networks are used to reveal crucial changes among different biological states, which reflect on the development of living organisms. It is critical to discover the kernel differential subgraph (KDS) that leads to drastic changes. However, identifying the KDS is similar to the Steiner Tree problem that is an NP-hard problem. In this paper, we developed a criterion to explore the KDS (CKDS), which considered the connectivity and scale of KDS, the topological difference of nodes and function relevance between genes in the KDS. The CKDS algorithm was applied to simulated datasets and three single-cell RNA sequencing (scRNA-seq) datasets including GBM, fetal human cortical neurons (FHCN) and neural differentiation. Then we performed the network topology and functional enrichment analyses on the extracted KDSs. Compared with the state-of-art methods, the CKDS algorithm outperformed on simulated datasets to discover the KDSs. In the GBM and FHCN, seventeen genes (one biomarker, nine regulatory genes, one driver genes, six therapeutic targets) and KEGG pathways in KDSs were strongly supported by literature mining that they were highly interrelated with GBM. Moreover, focused on GBM, there were fifteen genes (including ten regulatory genes, three driver genes, one biomarkers, one therapeutic target) and KEGG pathways found in the KDS of neural differentiation process from activated neural stem cells (aNSC) to neural progenitor cells (NPC), while few genes and no pathway were found in the period from NPC to astrocytes (Ast). These experiments indicated that the process from aNSC to NPC is a key differentiation period affecting the development of GBM. Therefore, the CKDS algorithm provides a unique perspective in identifying cell-type-specific genes and KDSs.
RETRACTED: Role of Serum and Urine Biomarkers (PLA2R and THSD7A) in Diagnosis, Monitoring and Prognostication of Primary Membranous Glomerulonephritis
Authors: Maifata Sadiq , Hod Rafidah , Zakaria Fadhlina , Abd Ghani Fauzah
Published: February 2020

Differentiating primary and secondary membranous glomerulonephritis (MGN) using biomarkers for MGN is essential in patients’ diagnosis, treatment and follow-up. Although biopsy has been the primary tool in making the diagnosis, not all patients can withstand it due to its invasive nature, and it cannot be used to monitor treatment. Hence, there is the need for less invasive or even non-invasive biomarkers for effective diagnosis, treatment monitoring and prognostication. This study aimed at providing an alternative way of differentiating primary and secondary MGN using enzyme-linked immunosorbent assay (ELISA) technique for serum and urine biomarkers (M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A)) for prompt diagnosis, treatment and prognosis. A total of 125 subjects, including 81 primary and 44 secondary MGN subjects, were diagnosed from January 2012 to October 2019 at Hospital Serdang and Hospital Kuala Lumpur from which 69 subjects consisting of 47 primary and 22 secondary MGN subjects participated in the study. Of these, 13 primary MGN subjects were positive for both serum and urine anti-PLA2R antibodies (Ab) whereas only one secondary MGN subject associated with hepatitis B virus was positive for both serum and urine anti-PLA2R Ab. At the same time, anti-THSD7A Ab was found positive in four primary MGN subjects and two secondary MGN subjects with malignancy.
The Relevance of Thimet Oligopeptidase in the Regulation of Energy Metabolism and Diet-Induced Obesity
Authors: Gewehr Mayara C. F. , Teixeira Alexandre A. S. , Santos Bruna A. C. , Biondo Luana A. , Gozzo Fábio C. , Cordibello Amanda M. , Eichler Rosangela A. S. , Reckziegel Patrícia , Da Silva Renée N. O. , Dos Santos Nilton B. , Camara Niels O. S. , Castoldi Angela , Barreto-Chaves Maria L. M. , Dale Camila S. , Senger Nathalia , Lima Joanna D. C. C. , Seelaender Marilia C. L. , Inada Aline C. , Akamine Eliana H. , Castro Leandro M. , Rodrigues Alice C. , Rosa Neto José C. , Ferro Emer S.
Published: February 2020

Thimet oligopeptidase (EC 3.4.24.15; EP24.15; THOP1) is a potential therapeutic target, as it plays key biological functions in processing biologically functional peptides. The structural conformation of THOP1 provides a unique restriction regarding substrate size, in that it only hydrolyzes peptides (optimally, those ranging from eight to 12 amino acids) and not proteins. The proteasome activity of hydrolyzing proteins releases a large number of intracellular peptides, providing THOP1 substrates within cells. The present study aimed to investigate the possible function of THOP1 in the development of diet-induced obesity (DIO) and insulin resistance by utilizing a murine model of hyperlipidic DIO with both C57BL6 wild-type (WT) and THOP1 null (THOP1−/−) mice. After 24 weeks of being fed a hyperlipidic diet (HD), THOP1−/− and WT mice ingested similar chow and calories; however, the THOP1−/− mice gained 75% less body weight and showed neither insulin resistance nor non-alcoholic fatty liver steatosis when compared to WT mice. THOP1−/− mice had increased adrenergic-stimulated adipose tissue lipolysis as well as a balanced level of expression of genes and microRNAs associated with energy metabolism, adipogenesis, or inflammation. Altogether, these differences converge to a healthy phenotype of THOP1−/− fed a HD. The molecular mechanism that links THOP1 to energy metabolism is suggested herein to involve intracellular peptides, of which the relative levels were identified to change in the adipose tissue of WT and THOP1−/− mice. Intracellular peptides were observed by molecular modeling to interact with both pre-miR-143 and pre-miR-222, suggesting a possible novel regulatory mechanism for gene expression. Therefore, we successfully demonstrated the previously anticipated relevance of THOP1 in energy metabolism regulation. It was suggested that intracellular peptides were responsible for mediating the phenotypic differences that are described herein by a yet unknown mechanism of action.
Reduced Local Response to Corticosteroids in Eosinophilic Chronic Rhinosinusitis with Asthma
Authors: Kobayashi Yoshiki , Kanda Akira , Yun Yasutaka , Bui Dan Van , Suzuki Kensuke , Sawada Shunsuke , Asako Mikiya , Iwai Hiroshi
Published: February 2020

Eosinophilic chronic rhinosinusitis (ECRS), a subgroup of chronic rhinosinusitis with nasal polyps, is recognized as a refractory eosinophilic disorder characterized by both upper and lower airway inflammation. In some severe cases, disease control is poor, likely due to local steroid insensitivity. In this study, we focused on protein phosphatase 2A (PP2A), a key factor regulating glucocorticoid receptor (GR) nuclear translocation, and examined its association with local responses to corticosteroids in eosinophilic airway inflammation. Our results indicated reduced responses to corticosteroids in nasal epithelial cells from ECRS patients with asthma, which were also associated with decreased PP2A mRNA expression. Eosinophil peroxidase stimulates elevated PP2A phosphorylation levels, reducing PP2A protein expression and activity. In addition, mRNA levels of inflammatory mediators (TSLP, IL-25, IL-33, CCL4, CCL5, CCL11, and CCL26) associated with eosinophilic airway inflammation in epithelial cells were increased in nasal polyps (eosinophil-rich areas) compared with those in uncinate process tissues (eosinophil-poor areas) from the same patients. PP2A reduction by siRNA reduced GR nuclear translocation, whereas PP2A overexpression by plasmid transfection, or PP2A activation by formoterol, enhanced GR nuclear translocation. Collectively, our findings indicate that PP2A may represent a promising therapeutic target in refractory eosinophilic airway inflammation characterized by local steroid insensitivity.
Characterization of the CRM Gene Family and Elucidating the Function of OsCFM2 in Rice
Authors: Zhang Qiang , Shen Lan , Ren Deyong , Hu Jiang , Zhu Li , Gao Zhenyu , Zhang Guangheng , Guo Longbiao , Zeng Dali , Qian Qian
Published: February 2020

The chloroplast RNA splicing and ribosome maturation (CRM) domain-containing proteins regulate the expression of chloroplast or mitochondrial genes that influence plant growth and development. Although 14 CRM domain proteins have previously been identified in rice, there are few studies of these gene expression patterns in various tissues and under abiotic stress. In our study, we found that 14 CRM domain-containing proteins have a conservative motif1. Under salt stress, the expression levels of 14 CRM genes were downregulated. However, under drought and cold stress, the expression level of some CRM genes was increased. The analysis of gene expression patterns showed that 14 CRM genes were expressed in all tissues but especially highly expressed in leaves. In addition, we analyzed the functions of OsCFM2 and found that this protein influences chloroplast development by regulating the splicing of a group I and five group II introns. Our study provides information for the function analysis of CRM domain-containing proteins in rice.
Notch Signaling in Skeletal Development, Homeostasis and Pathogenesis
Authors: Zieba Jennifer T. , Chen Yi-Ting , Lee Brendan H. , Bae Yangjin
Published: February 2020

Skeletal development is a complex process which requires the tight regulation of gene activation and suppression in response to local signaling pathways. Among these pathways, Notch signaling is implicated in governing cell fate determination, proliferation, differentiation and apoptosis of skeletal cells-osteoblasts, osteoclasts, osteocytes and chondrocytes. Moreover, human genetic mutations in Notch components emphasize the critical roles of Notch signaling in skeletal development and homeostasis. In this review, we focus on the physiological roles of Notch signaling in skeletogenesis, postnatal bone and cartilage homeostasis and fracture repair. We also discuss the pathological gain- and loss-of-function of Notch signaling in bone and cartilage, resulting in osteosarcoma and age-related degenerative diseases, such as osteoporosis and osteoarthritis. Understanding the physiological and pathological function of Notch signaling in skeletal tissues using animal models and human genetics will provide new insights into disease pathogenesis and offer novel approaches for the treatment of bone/cartilage diseases.
Hyperarousal Is Associated with Socioemotional Processing in Individuals with Insomnia Symptoms and Good Sleepers
Authors: Howlett Reuben D. M. , Lustig Kari A. , MacDonald Kevin J. , Cote Kimberly A.
Published: February 2020

Despite complaints of difficulties in waking socioemotional functioning by individuals with insomnia, only a few studies have investigated emotion processing performance in this group. Additionally, the role of sleep in socioemotional processing has not been investigated extensively nor using quantitative measures of sleep. Individuals with insomnia symptoms (n = 14) and healthy good sleepers (n = 15) completed two nights of at-home polysomnography, followed by an afternoon of in-lab performance testing on tasks measuring the processing of emotional facial expressions. The insomnia group self-reported less total sleep time, but no other group differences in sleep or task performance were observed. Greater beta EEG power throughout the night was associated with higher intensity ratings of happy, fearful and sad faces for individuals with insomnia, yet blunted sensitivity and lower accuracy for good sleepers. Thus, the presence of hyperarousal differentially impacted socioemotional processing of faces in individuals with insomnia symptoms and good sleepers.
Brain Processing of Complex Geometric Forms in a Visual Memory Task Increases P2 Amplitude
Authors: Cepeda-Freyre Héctor A. , Garcia-Aguilar Gregorio , Eguibar Jose R. , Cortes Carmen
Published: February 2020

We study the cognitive processing of visual working memory in three different conditions of memory load and configuration change. Altering this features has been shown to alter the brain’s processing in memory tasks. Most studies dealing with this issue have used the verbal-phonological modality. We use complex geometric polygons to assess visual working memory in a modified change detection task. Three different types of backgrounds were used to manipulate memory loading and 18 complex geometric polygons to manipulate stimuli configuration. The goal of our study was to test whether the memory load and configuration affect the correct-recall ratios. We expected that increasing visual items loading and changing configuration of items would induce differences in working memory performance. Brain activity related to the task was assessed through event-related potentials (ERP), during the test phase of each trial. Our results showed that visual items loading and changing of item configuration affect working memory on test phase on ERP component P2, but does not affect performance. However frontal related ERP component—P3—was minimally affected by visual memory loading or configuration changing, supporting that working memory is related to a filtering processing in posterior brain regions.
Random Forest Classification of Alcohol Use Disorder Using fMRI Functional Connectivity, Neuropsychological Functioning, and Impulsivity Measures
Authors: Kamarajan Chella , Ardekani Babak A. , Pandey Ashwini K. , Kinreich Sivan , Pandey Gayathri , Chorlian David B. , Meyers Jacquelyn L. , Zhang Jian , Bermudez Elaine , Stimus Arthur T. , Porjesz Bernice
Published: February 2020

Individuals with alcohol use disorder (AUD) are known to manifest a variety of neurocognitive impairments that can be attributed to alterations in specific brain networks. The current study aims to identify specific features of brain connectivity, neuropsychological performance, and impulsivity traits that can classify adult males with AUD (n = 30) from healthy controls (CTL, n = 30) using the Random Forest (RF) classification method. The predictor variables were: (i) fMRI-based within-network functional connectivity (FC) of the Default Mode Network (DMN), (ii) neuropsychological scores from the Tower of London Test (TOLT), and the Visual Span Test (VST), and (iii) impulsivity factors from the Barratt Impulsiveness Scale (BIS). The RF model, with a classification accuracy of 76.67%, identified fourteen DMN connections, two neuropsychological variables (memory span and total correct scores of the forward condition of the VST), and all impulsivity factors as significantly important for classifying participants into either the AUD or CTL group. Specifically, the AUD group manifested hyperconnectivity across the bilateral anterior cingulate cortex and the prefrontal cortex as well as between the bilateral posterior cingulate cortex and the left inferior parietal lobule, while showing hypoconnectivity in long-range anterior–posterior and interhemispheric long-range connections. Individuals with AUD also showed poorer memory performance and increased impulsivity compared to CTL individuals. Furthermore, there were significant associations among FC, impulsivity, neuropsychological performance, and AUD status. These results confirm the previous findings that alterations in specific brain networks coupled with poor neuropsychological functioning and heightened impulsivity may characterize individuals with AUD, who can be efficiently identified using classification algorithms such as Random Forest.