bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrafine TaOx/CB Oxygen Reduction Electrocatalyst Operating in Both Acidic and Alkaline Media
Authors: Park Jun-Woo , Seo Jeongsuk
Published: December 2021

The high activity of non-platinum electrocatalysts for oxygen reduction reaction (ORR) in alkaline media is necessary for applications in energy conversion devices such as fuel cells and metal-air batteries. Herein, we present the electrocatalytic activity of TaOx/carbon black (CB) nanoparticles for the ORR in an alkaline atmosphere as well as in an acidic electrolyte. Ultrafine TaOx nanoparticles 1–2 nm in size and uniformly dispersed on CB supports were prepared by potentiostatic electrodeposition in a nonaqueous electrolyte and subsequent annealing treatment in an H2 flow. The TaOx/CB nanoparticles largely catalyzed the ORR with an onset potential of 1.03 VRHE in an O2-saturated 0.1 M KOH solution comparable to that of a commercial Pt/CB catalyst. ORR activity was also observed in 0.1 M H2SO4 solution. According to the rotating ring disk electrode measurement results, the oxide nanoparticles partly produced H2O2 during the ORR in 0.1 M KOH, and the ORR process was dominated by both the two- and four-electron reductions of oxygen in a diffusion-limited potential region. The Tafel slope of −120 mV dec−1 in low and high current densities revealed the surface stability of the oxide nanoparticles during the ORR. Therefore, these results demonstrated that the TaOx/CB nanoparticles were electroactive for the ORR in both acidic and alkaline electrolytes.
The Role of LIM Kinase in the Male Urogenital System
Authors: Park Juhyun , Kim Soo Woong , Cho Min Chul
Published: December 2021

The LIM kinases (LIMK1 and LIMK2), known as downstream effectors, and the Rho-associated protein kinase (ROCK), a regulator of actin dynamics, have effects on a diverse set of cellular functions. The LIM kinases are involved in the function of the male urogenital system by smooth muscle contraction via phosphorylation of cofilin and subsequent actin cytoskeleton reorganization. Although LIMK1 and LIMK2 share sequence similarities as serine protein kinases, different tissue distribution patterns and distinct localization during cell cycle progression suggest other biological functions for each kinase. During meiosis and mitosis, the LIMK1/2–cofilin signaling facilitates the orchestrated chromatin remodeling between gametogenesis and the actin cytoskeleton. A splicing variant of the LIMK2 transcript was expressed only in the testis. Moreover, positive signals with LIMK2-specific antibodies were detected mainly in the nucleus of the differentiated stages of germ cells, such as spermatocytes and early round spermatids. LIMK2 plays a vital role in proper spermatogenesis, such as meiotic processes of spermatogenesis after puberty. On the other hand, the literature evidence revealed that a reduction in LIMK1 expression enhanced the inhibitory effects of a ROCK inhibitor on the smooth muscle contraction of the human prostate. LIMK1 may have a role in urethral obstruction and bladder outlet obstruction in men with benign prostatic hyperplasia. Moreover, LIMK1 expression was reduced in urethral stricture. The reduced LIMK1 expression caused the impaired proliferation and migration of urethral fibroblasts. In addition, the activated LIMK2–cofilin pathway contributes to cavernosal fibrosis after cavernosal nerve injury. Recent evidence demonstrated that short-term inhibition of LIMK2 from the immediate post-injury period prevented cavernosal fibrosis and improved erectile function in a rat model of cavernosal nerve injury. Furthermore, chronic inhibition of the LIMK2–cofilin pathway significantly restrained the cavernosal veno-occlusive dysfunction, the primary pathophysiologic mechanism of post-prostatectomy erectile dysfunction through suppressing fibrosis in the corpus cavernosum. In conclusion, the LIM kinases–cofilin pathway appears to play a role in the function of the male urogenital system through actin cytoskeleton reorganization and contributes to the pathogenesis of several urogenital diseases. Therefore, LIM kinases may be a potential treatment target in urogenital disorder.
Interpretable Autoencoders Trained on Single Cell Sequencing Data Can Transfer Directly to Data from Unseen Tissues
Authors: Walbech Julie Sparholt , Kinalis Savvas , Winther Ole , Nielsen Finn Cilius , Bagger Frederik Otzen
Published: December 2021

Autoencoders have been used to model single-cell mRNA-sequencing data with the purpose of denoising, visualization, data simulation, and dimensionality reduction. We, and others, have shown that autoencoders can be explainable models and interpreted in terms of biology. Here, we show that such autoencoders can generalize to the extent that they can transfer directly without additional training. In practice, we can extract biological modules, denoise, and classify data correctly from an autoencoder that was trained on a different dataset and with different cells (a foreign model). We deconvoluted the biological signal encoded in the bottleneck layer of scRNA-models using saliency maps and mapped salient features to biological pathways. Biological concepts could be associated with specific nodes and interpreted in relation to biological pathways. Even in this unsupervised framework, with no prior information about cell types or labels, the specific biological pathways deduced from the model were in line with findings in previous research. It was hypothesized that autoencoders could learn and represent meaningful biology; here, we show with a systematic experiment that this is true and even transcends the training data. This means that carefully trained autoencoders can be used to assist the interpretation of new unseen data.
PPARγ Regulates Triclosan Induced Placental Dysfunction
Authors: Li Jing , Quan Xiaojie , Zhang Yue , Yu Ting , Lei Saifei , Huang Zhenyao , Wang Qi , Song Weiyi , Yang Xinxin , Xu Pengfei
Published: December 2021

Exposure to the antibacterial agent triclosan (TCS) is associated with abnormal placenta growth and fetal development during pregnancy. Peroxisome proliferator-activated receptor γ (PPARγ) is crucial in placenta development. However, the mechanism of PPARγ in placenta injury induced by TCS remains unknown. Herein, we demonstrated that PPARγ worked as a protector against TCS-induced toxicity. TCS inhibited cell viability, migration, and angiogenesis dose-dependently in HTR-8/SVneo and JEG-3 cells. Furthermore, TCS downregulated expression of PPARγ and its downstream viability, migration, angiogenesis-related genes HMOX1, ANGPTL4, VEGFA, MMP-2, MMP-9, and upregulated inflammatory genes p65, IL-6, IL-1β, and TNF-α in vitro and in vivo. Further investigation showed that overexpression or activation (rosiglitazone) alleviated cell viability, migration, angiogenesis inhibition, and inflammatory response caused by TCS, while knockdown or inhibition (GW9662) of PPARγ had the opposite effect. Moreover, TCS caused placenta dysfunction characterized by the significant decrease in weight and size of the placenta and fetus, while PPARγ agonist rosiglitazone alleviated this damage in mice. Taken together, our results illustrated that TCS-induced placenta dysfunction, which was mediated by the PPARγ pathway. Our findings reveal that activation of PPARγ might be a promising strategy against the adverse effects of TCS exposure on the placenta and fetus.
The Alpha-Synuclein RT-QuIC Products Generated by the Olfactory Mucosa of Patients with Parkinson’s Disease and Multiple System Atrophy Induce Inflammatory Responses in SH-SY5Y Cells
Authors: De Luca Chiara Maria Giulia , Consonni Alessandra , Cazzaniga Federico Angelo , Bistaffa Edoardo , Bufano Giuseppe , Quitarrini Giorgia , Celauro Luigi , Legname Giuseppe , Eleopra Roberto , Baggi Fulvio , Giaccone Giorgio , Moda Fabio
Published: December 2021

Parkinson’s disease (PD) and multiple system atrophy (MSA) are caused by two distinct strains of disease-associated α-synuclein (αSynD). Recently, we have shown that olfactory mucosa (OM) samples of patients with PD and MSA can seed the aggregation of recombinant α-synuclein by means of Real-Time Quaking-Induced Conversion (αSyn_RT-QuIC). Remarkably, the biochemical and morphological properties of the final α-synuclein aggregates significantly differed between PD and MSA seeded samples. Here, these aggregates were given to neuron-like differentiated SH-SY5Y cells and distinct inflammatory responses were observed. To deepen whether the morphological features of α-synuclein aggregates were responsible for this variable SH-SY5Y inflammatory response, we generated three biochemically and morphologically distinct α-synuclein aggregates starting from recombinant α-synuclein that were used to seed αSyn_RT-QuIC reaction; the final reaction products were used to stimulate SH-SY5Y cells. Our study showed that, in contrast to OM samples of PD and MSA patients, the artificial aggregates did not transfer their distinctive features to the αSyn_RT-QuIC products and the latter induced analogous inflammatory responses in cells. Thus, the natural composition of the αSynD strains but also other specific factors in OM tissue can substantially modulate the biochemical, morphological and inflammatory features of the αSyn_RT-QuIC products.
Findings and Graduation of Sarcoidosis-Related Uveitis: A Single-Center Study
Authors: zur Bonsen Lynn S. , Pohlmann Dominika , Rübsam Anne , Pleyer Uwe
Published: December 2021

Ocular involvement is present in up to 79% of sarcoid patients. Uveitis is the main ocular manifestation and presents as a chronic intraocular inflammatory condition with potentially detrimental effects on visual acuity and quality of life. This retrospective study was conducted to explore the incidence and characteristics of ocular sarcoidosis in a single tertiary ophthalmology center. Medical records of 84 patients presenting between June 2007 and March 2021 were analyzed. Based on the “International Workshop on Ocular Sarcoidosis” (IWOS) criteria, ocular sarcoidosis was determined as: definite (n = 24; 28.6%), presumed (n = 33; 39.3%), probable (n = 10; 11.9%), and indefinite (n = 17; 20.2%) in our study population. In 43.9% of the definite and presumed cases, the eye was primarily affected. In addition to specific ocular findings, the diagnosis was supported by biopsy (28.6%) and chest x-ray or computer tomography (66.7%). Moreover, an increased soluble interleukin-2 receptor (sIL-2R) expression (76.2%), elevated angiotensin-converting enzyme (ACE) levels (34.8%), and lymphocytopenia (35.1%) were valuable laboratory findings. Co-affected organs were lungs (60.7%), skin (15.5%), and central nervous system (8.3%). Our findings support the prominent role of the eye in the early detection of sarcoidosis. In addition to the IWOS criteria, sIL-2R, in particular, was shown to be relevant in establishing the diagnosis.
Potassium Effects on NCC Are Attenuated during Inhibition of Cullin E3–Ubiquitin Ligases
Authors: Murali Sathish K. , Little Robert , Poulsen Søren B. , Ferdaus Mohammed Z. , Ellison David H. , McCormick James A. , Fenton Robert A.
Published: December 2021

The thiazide-sensitive sodium chloride cotransporter (NCC) plays a vital role in maintaining sodium (Na+) and potassium (K+) homeostasis. NCC activity is modulated by with-no-lysine kinases 1 and 4 (WNK1 and WNK4), the abundance of which is controlled by the RING-type E3 ligase Cullin 3 (Cul3) and its substrate adapter Kelch-like protein 3. Dietary K+ intake has an inverse correlation with NCC activity, but the mechanism underlying this phenomenon remains to be fully elucidated. Here, we investigated the involvement of other members of the cullin family in mediating K+ effects on NCC phosphorylation (active form) and abundance. In kidneys from mice fed diets varying in K+ content, there were negative correlations between NCC (phosphorylated and total) and active (neddylated) forms of cullins (Cul1, 3, 4, and 5). High dietary K+ effects on phosphorylated NCC were attenuated in Cul3 mutant mice (CUL3-Het/Δ9). Short-term (30 min) and long-term (24 h) alterations in the extracellular K+ concentration did not affect cullin neddylation levels in ex vivo renal tubules. In the short term, the ability of high extracellular K+ to decrease NCC phosphorylation was preserved in the presence of MLN4924 (pan-cullin inhibitor), but the response to low extracellular K+ was absent. In the long term, MLN4924 attenuated the effects of high extracellular K+ on NCC phosphorylation, and responses to low extracellular K+ were absent. Our data suggest that in addition to Cul3, other cullins are involved in mediating the effects of K+ on NCC phosphorylation and abundance.
Autophagy and Endoplasmic Reticulum Stress during Onset and Progression of Arrhythmogenic Cardiomyopathy
Authors: Pitsch Mark , Kant Sebastian , Mytzka Corinna , Leube Rudolf E. , Krusche Claudia A.
Published: December 2021

Arrhythmogenic cardiomyopathy (AC) is a heritable, potentially lethal disease without a causal therapy. AC is characterized by focal cardiomyocyte death followed by inflammation and progressive formation of connective tissue. The pathomechanisms leading to structural disease onset and progression, however, are not fully elucidated. Recent studies revealed that dysregulation of autophagy and endoplasmic/sarcoplasmic reticulum (ER/SR) stress plays an important role in cardiac pathophysiology. We therefore examined the temporal and spatial expression patterns of autophagy and ER/SR stress indicators in murine AC models by qRT-PCR, immunohistochemistry, in situ hybridization and electron microscopy. Cardiomyocytes overexpressing the autophagy markers LC3 and SQSTM1/p62 and containing prominent autophagic vacuoles were detected next to regions of inflammation and fibrosis during onset and chronic disease progression. mRNAs of the ER stress markers Chop and sXbp1 were elevated in both ventricles at disease onset. During chronic disease progression Chop mRNA was upregulated in right ventricles. In addition, reduced Ryr2 mRNA expression together with often drastically enlarged ER/SR cisternae further indicated SR dysfunction during this disease phase. Our observations support the hypothesis that locally altered autophagy and enhanced ER/SR stress play a role in AC pathogenesis both at the onset and during chronic progression.
The Effect of Incorporating an Exergame Application in a Multidisciplinary Weight Management Program on Physical Activity and Fitness Indices in Children with Overweight and Obesity
Authors: Kahana Rotem , Kremer Shai , Dekel Dahari Merav , Kodesh Einat
Published: December 2021

Children with overweight/obese (OW/OB) have low physical activity (PA) levels and excessive daily screen times. Although access to personal smartphones may complicate restricting sedentary screen time, these devices may be used to promote PA and improve fitness. Therefore, we aim to examine the impact of incorporating an exergame application (APP) into an existing weight management program on BMI, physical activity, fitness levels, and attitude toward PA among OW/OB children. Seventy-nine children (51% girls), median age 10 years, completed an established 5-month weight management program. The intervention included structured PA sessions (2/week), nutritional, and behavioral counseling. An exergame app was installed on the smartphones of the intervention group (APP, n = 32). BMI, physical fitness, PA level, and attitudes toward PA were assessed before and after the intervention. BMI decreased (p < 0.0001) in both groups by 0.67 kg/m2 (Q1, Q3: −1.36–0.12). There were improvements in more fitness components in the APP group than controls, with significantly greater improvements in aerobic fitness (p = 0.038), speed and agility (p = 0.01), and leg strength endurance (p = 0.05) compared to controls. PA levels increased similarly in both groups during the intervention period. The incorporation of an exergame application leads to more significant improvements in fitness components. These findings support the use of exergame apps to improve fitness in OW/OB children.
Tantalum-Titanium Oxynitride Thin Films Deposited by DC Reactive Magnetron Co-Sputtering: Mechanical, Optical, and Electrical Characterization
Authors: Cristea Daniel , Velicu Ioana-Laura , Cunha Luis , Barradas Nuno , Alves Eduardo , Craciun Valentin
Published: December 2021

The possibility to tune the elemental composition and structure of binary Me oxynitride-type compounds (Me1Me2ON) could lead to attractive properties for several applications. For this work, tantalum-titanium oxynitride (TaTiON) thin films were deposited by DC reactive magnetron co-sputtering, with a –50 V bias voltage applied to the substrate holder and a constant substrate temperature of 100 °C. To increase or to decrease in a controlled manner, the Ti and Ta content in the co-sputtered films, the Ti and Ta target currents were varied between 0.00 and 1.00 A, in 0.25 A steps, while keeping the sum of the currents applied to the two targets at 1.00 A. The reactive gases flow, consisting of a nitrogen and oxygen gas mixture with a constant N2/O2 ratio (85%/15%), was also kept constant. The single-metal oxynitrides (TaON and TiON) showed a low degree of crystallinity, while all the other co-sputtered films revealed themselves to be essentially amorphous. These two films also exhibited higher adhesion to the metallic substrate. The TaON film showed the highest hardness value (14.8 GPa) and the TiON film a much lower one (8.8 GPa), while the co-sputtered coatings exhibited intermediary values. One of the most interesting findings was the significant increase in the O content when the Ti concentration surpassed the Ta one. This significantly influenced the optical characteristic of the films, but also their electrical properties. The sheet resistivity of the co-sputtered films is strongly dependent on the O/(Ta + Ti) atomic ratio.
Application of Artificial Neural Networks in Analysis of Time-Variable Optical Reflectance Spectra in Digital Light Projection Spectroscopy
Authors: Gąsiorowski Marek , Szymak Piotr , Bychto Leszek , Patryn Aleksy
Published: December 2021

This article undertakes the subject matter of applying artificial neural networks to analyze optical reflectance spectra of objects exhibiting a change of optical properties in the domain of time. A compact Digital Light Projection NIRscan Nano Evaluation Module spectrometer was used to record spectra. Due to the miniature spectrometer’s size and its simplicity of measurement, it can be used to conduct tests outside of a laboratory. A series of plant-derived objects were used as test subjects with rapidly changing optical properties in the presented research cycle. The application of artificial neural networks made it possible to determine the aging time of plants with a relatively low mean squared error, reaching 0.56 h for the Levenberg–Marquardt backpropagation training method. The results of the other ten training methods for artificial neural networks have been included in the paper.
Effect of Polyurethane Non-Transparent Coating Process on Paint Film Performance Applied on Modified Poplar
Authors: Liu Qingqing , Gao Di , Xu Wei
Published: December 2021

Whether modified poplar can obtain a qualified or even excellent finishing effect on European and American furniture is worthy of deep study. To evaluate whether the conventional non-transparent coating process is suitable for modified poplar, a multi-level hybrid orthogonal experiment method was carried out to start research on how factors affect the paint film performance of the non-transparent coating process. The effect of experimental factors and levels on paint film performance is pointed out, and the optimal factors and levels are found. Parameter optimization of the polyurethane non-transparent finishing process based on modified poplar is carried out. An application basis was provided for the extensive use of modified poplar wood as a substrate in the European and American furniture markets. The conclusions are: (1) gloss of paint film can be improved by increasing the number of nitrocellulose (NC) lacquer transparent topcoats, (2) adhesion and thickness of paint film can be improved by polyurethane (PU) sealing primer, (3) the initial paint film’s abrasion is influenced efficiently by the coating process and coating sanding. PU sealing primer has an efficient influence on the later abrasion of paint film. The effect of modified poplar surface pretreatment on the mass loss of paint film tends to be stable.
Effect of Arc Currents on the Mechanical, High Temperature Oxidation and Corrosion Properties of CrSiN Nanocomposite Coatings
Authors: Xiang Yanxiong , Zou Changwei
Published: December 2021

In methods for multi-arc ion plating technology, the behavior and characteristics of the arc spot determine the physical characteristics of arc plasma and the properties of the subsequent deposited coatings. In this paper, the effect of arc currents on the hardness, friction coefficient, high temperature oxidation, and corrosion properties of the CrSiN coatings was studied. According to the XRD and SEM results, with the increase of arc currents, the coatings grew preferentially to the CrN (111) crystal direction, and the CrN (220) crystal phase appeared at high currents of 90 A. In addition, the number of large particles increased when the current exceeded 70 A. The HR-TEM results confirmed the formation of nanocomposite structure of nanocrystalline of CrN embedded into the amorphous phase of Si3N4 as explored by XRD. The maximum hardness was achieved at 3120 Hv when the coatings were deposited under currents around 70 A. However, the hardness values decreased with further increase of arc currents. From the contact of ceramic balls with the wear of coatings, the surface of coatings gradually produced friction marks, and the friction force increased from a steady friction force to a dynamic friction force. The high temperature oxidation results showed that fewer oxides were formed on the surface of the coatings when oxidized at 800 °C. It was also found that CrSiN nanocomposite coatings prepared at an arc current of 70 A had a larger corrosion potential and polarization impedance, which could effectively protect the tool matrix.
Wear Resistance of Aluminum Matrix Composites’ Coatings Added on AA6082 Aluminum Alloy by Laser Cladding
Authors: Riquelme Ainhoa , Rodrigo Pilar , Escalera-Rodriguez María Dolores , Rams Joaquin
Published: December 2021

Ceramic-reinforced metal matrix composites are known for their high wear resistance. A coating based on these materials would be helpful to improve the wear behavior of aluminum alloys. Laser cladding has been used to deposit a coating consisting of an aluminum alloy reinforced with SiC particles on an AA6082 aluminum alloy. Laser cladding is a very energetic technique that causes the SiC particles to react with the molten aluminum to form Al4C3, which degrades the particles and reduces the properties of the coating. The formation of this detrimental compound was successfully achieved with the addition of Silicon and Titanium to the composite matrix. The microstructures of the newly developed material were characterized and the wear behavior was studied under dry sliding conditions on a pin-on-disc tribometer. The relationship between the microstructure and wear behavior was identified. The absence of Al4C3 in the Al40Si/SiC and Al12Si20Ti/SiC coatings’ microstructures resulted in an abrasion mechanism instead of a delamination mechanism. The wear behavior changed along the sliding distances. During the first 200 m of sliding distances, the wear rate of all coatings was lower than the uncoated one due to their higher microhardness. For longer sliding distances, the wear resistance of the uncoated AA6082 was higher than the coated ones due to the formation of a lubricant oxide layer on the AA6082 worn surface. For 1000 m of wear distances, the wear behavior was different for each coating. The wear rate of the Al12Si/SiC coating continued growing due to the delamination mechanism and the presence of Al4C3 that acted as starting crack points. The wear rate of the Al40Si/SiC coating decreased due to the formation of a thin, superficial oxide layer. The wear rate of the Al12SiTi/SiC progressively decreased along the sliding distance to below the substrate wear rate.
Simultaneous Detection of Seven Human Coronaviruses by Multiplex PCR and MALDI-TOF MS
Authors: Liu Tingting , Kang Lin , Li Yanwei , Huang Jing , Guo Zishuo , Xu Jinglin , Hu Yi , Zhai Zhixiang , Kang Xiaoping , Jiang Tao , Li Hao , Song Hexing , Wang Jing , Gao Shan , Li Jiaxin , Zhou Xiaoguang , Yuan Yuan , Zhao Baohua , Wang Jinglin , Xin Wenwen
Published: December 2021

Human coronaviruses (HCoVs) are associated with a range of respiratory symptoms. The discovery of severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome, and SARS-CoV-2 pose a significant threat to human health. In this study, we developed a method (HCoV-MS) that combines multiplex PCR with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), to detect and differentiate seven HCoVs simultaneously. The HCoV-MS method had high specificity and sensitivity, with a 1–5 copies/reaction detection limit. To validate the HCoV-MS method, we tested 163 clinical samples, and the results showed good concordance with real-time PCR. Additionally, the detection sensitivity of HCoV-MS and real-time PCR was comparable. The HCoV-MS method is a sensitive assay, requiring only 1 μL of a sample. Moreover, it is a high-throughput method, allowing 384 samples to be processed simultaneously in 30 min. We propose that this method be used to complement real-time PCR for large-scale screening studies.
The Interaction of the 2D MoP2 and NbP2 Surfaces with Carbon Dioxide and Carbon Monoxide and Changes in Their Optical Properties
Authors: Salas Osiris , Garcés Eric , Magana Luis Fernando
Published: December 2021

Using first-principles molecular dynamics (FPMD) simulations at atmospheric pressure and 300 K, we investigated the adsorption of the molecules CO and CO2 on each of the surfaces of the 2D materials MoP2 and NbP2. We found that both surfaces adsorbed the carbon monoxide molecule but not the carbon dioxide. The adsorption energy on the MoP2 surface was −0.9398 eV, and on the NbP2 surface, −0.9017 eV. Furthermore, we obtained substantial changes in the optical properties of each 2D material after the CO adsorption. For the two materials, the optical absorption shows significant changes in the ultraviolet region. Furthermore, the two surfaces present essential changes in the ultraviolet range in the case of reflectivity.
Sequence Analysis and Preliminary X-ray Crystallographic Analysis of an Acetylesterase (LgEstI) from Lactococcus garvieae
Authors: Do Hackwon , Wang Ying , Lee Chang Woo , Yoo Wanki , Jeon Sangeun , Hwang Jisub , Lee Min Ju , Kim Kyeong Kyu , Kim Han-Woo , Lee Jun Hyuck , Kim T. Doohun
Published: December 2021

A gene encoding LgEstI was cloned from a bacterial fish pathogen, Lactococcus garvieae. Sequence and bioinformatic analysis revealed that LgEstI is close to the acetyl esterase family and had maximum similarity to a hydrolase (UniProt: Q5UQ83) from Acanthamoeba polyphaga mimivirus (APMV). Here, we present the results of LgEstI overexpression and purification, and its preliminary X-ray crystallographic analysis. The wild-type LgEstI protein was overexpressed in Escherichia coli, and its enzymatic activity was tested using p-nitrophenyl of varying lengths. LgEstI protein exhibited higher esterase activity toward p-nitrophenyl acetate. To better understand the mechanism underlying LgEstI activity and subject it to protein engineering, we determined the high-resolution crystal structure of LgEstI. First, the wild-type LgEstI protein was crystallized in 0.1 M Tris-HCl buffer (pH 7.1), 0.2 M calcium acetate hydrate, and 19% (w/v) PEG 3000, and the native X-ray diffraction dataset was collected up to 2.0 Å resolution. The crystal structure was successfully determined using a molecular replacement method, and structure refinement and model building are underway. The upcoming complete structural information of LgEstI may elucidate the substrate-binding mechanism and provide novel strategies for subjecting LgEstI to protein engineering.
Composition and Potential Functions of Rhizobacterial Communities in a Pioneer Plant from Andean Altiplano
Authors: Zhang Qian , Araya Macarena M. , Astorga-Eló Marcia , Velasquez Gabriela , Rilling Joaquin I. , Campos Marco , Sadowsky Michael J. , Jorquera Milko A. , Acuña Jacquelinne J.
Published: December 2021

Plant microbiota that associate with pioneer plants are essential to their growth and adaptation to harsh conditions found in the Central Volcanic Zone of the Andes. In this sense, the rhizosphere of pioneer species represents a unique opportunity to examine how bacterial communities are recruited and support the growth of plants under abiotic stress conditions, such low nutrient availability, high solar irradiation, water scarcity, soil salinity, etc. In this study, we explored the community composition and potential functions of rhizobacteria obtained from specimens of Parastrephia quadrangularis (Meyen) Cabrera, commonly called Tola, grown on the slopes of the Guallatiri, Isluga, and Lascar volcanoes in the Atacama Desert of Chile by using 16S rRNA amplicon sequencing. Sequence analysis showed that the Actinobacteria, Proteobacteria, Acidobacteria, and Bacteroidetes were the most abundant phyla of the rhizobacterial communities examined. A similar diversity, richness, and abundance of OTUs were also observed in rhizosphere samples obtained from different plants. However, most of OTUs were not shared, suggesting that each plant recruits a specific rhizobacterial communities independently of volcanoes slope. Analyses of predicted functional activity indicated that the functions were mostly attributed to chemoheterotrophy and aerobic chemoheterotrophy, followed by nitrogen cycling (nitrate reduction and denitrification), and animal parasites or symbionts. In addition, co-occurrence analysis revealed that complex rhizobacterial interactions occur in P. quadrangularis rhizosphere and that members of the Patulibacteraceae comprise a keystone taxon. This study extends our understanding on the composition and functions of the rhizobiome, which is pivotal for the adaptability and colonization of pioneer plant to harsh conditions of the Atacama Desert, widely recognized as the driest place on planet Earth.
Method for Segmentation and Hybrid Joining of Additive Manufactured Segments in Prototyping Using the Example of Trim Parts
Authors: König Nils , Schockenhoff Ferdinand , König Adrian , Diermeyer Frank
Published: December 2021

Rapid prototyping has become increasingly popular over the past years. However, its application is heavily confined to a part size that fits the small build volume of additive machines. This paper presents a universal design method to overcome this limitation while preserving the economic advantages of rapid prototyping over conventional processes. It segments large, thin-walled parts and joins the segments. The method aims to produce an assembly with minimal loss to the performance and characteristics of a solid part. Based on a set of requirements, a universal segmentation approach and a novel hybrid joint design combining adhesive bonding and press fitting are developed. This design allows for the force transmission, positioning, and assembly of the segments adaptive to their individual geometry. The method is tailored to fused deposition modeling (FDM) by minimizing the need for support structures and actively compensating for manufacturing tolerances. While a universal application cannot be guaranteed, the adaptive design was proven for a variety of complex geometries. Using automotive trim parts as an example, the usability, benefits, and novelty of the design method is presented. The method itself shows a high potential to overcome the build volume limitation for thin-walled parts in an economic manner.
WisecondorFF: Improved Fetal Aneuploidy Detection from Shallow WGS through Fragment Length Analysis
Authors: Mokveld Tom , Al-Ars Zaid , Sistermans Erik A. , Reinders Marcel
Published: December 2021

In prenatal diagnostics, NIPT screening utilizing read coverage-based profiles obtained from shallow WGS data is routinely used to detect fetal CNVs. From this same data, fragment size distributions of fetal and maternal DNA fragments can be derived, which are known to be different, and often used to infer fetal fractions. We argue that the fragment size has the potential to aid in the detection of CNVs. By integrating, in parallel, fragment size and read coverage in a within-sample normalization approach, it is possible to construct a reference set encompassing both data types. This reference then allows the detection of CNVs within queried samples, utilizing both data sources. We present a new methodology, WisecondorFF, which improves sensitivity, while maintaining specificity, relative to existing approaches. WisecondorFF increases robustness of detected CNVs, and can reliably detect even at lower fetal fractions (<2%).
Subgroup-Specific Diagnostic, Prognostic, and Predictive Markers Influencing Pediatric Medulloblastoma Treatment
Authors: Ray Sutapa , Chaturvedi Nagendra K. , Bhakat Kishor K. , Rizzino Angie , Mahapatra Sidharth
Published: December 2021

Medulloblastoma (MB) is the most common malignant central nervous system tumor in pediatric patients. Mainstay of therapy remains surgical resection followed by craniospinal radiation and chemotherapy, although limitations to this therapy are applied in the youngest patients. Clinically, tumors are divided into average and high-risk status on the basis of age, metastasis at diagnosis, and extent of surgical resection. However, technological advances in high-throughput screening have facilitated the analysis of large transcriptomic datasets that have been used to generate the current classification system, dividing patients into four primary subgroups, i.e., WNT (wingless), SHH (sonic hedgehog), and the non-SHH/WNT subgroups 3 and 4. Each subgroup can further be subdivided on the basis of a combination of cytogenetic and epigenetic events, some in distinct signaling pathways, that activate specific phenotypes impacting patient prognosis. Here, we delve deeper into the genetic basis for each subgroup by reviewing the extent of cytogenetic events in key genes that trigger neoplastic transformation or that exhibit oncogenic properties. Each of these discussions is further centered on how these genetic aberrations can be exploited to generate novel targeted therapeutics for each subgroup along with a discussion on challenges that are currently faced in generating said therapies. Our future hope is that through better understanding of subgroup-specific cytogenetic events, the field may improve diagnosis, prognosis, and treatment to improve overall quality of life for these patients.
Low Serum Levels of Soluble Receptor Activator of Nuclear Factor κ B Ligand (sRANKL) Are Associated with Metabolic Dysregulation and Predict Long-Term Mortality in Critically Ill Patients
Authors: Puengel Tobias , Weber Beate , Wirtz Theresa , Buendgens Lukas , Loosen Sven , Geisler Lukas , Özdirik Burcin , Hamesch Karim , Jhaisha Samira , Brozat Jonathan , Hohlstein Philipp , Eisert Albrecht , Yagmur Eray , Trautwein Christian , Tacke Frank , Koch Alexander
Published: December 2021

Soluble receptor activator of nuclear factor κ B ligand (sRANKL) is a member of the tumor necrosis factor receptor superfamily, and therefore, involved in various inflammatory processes. The role of sRANKL in the course of bone remodeling via activation of osteoclasts as well as chronic disease progression has been described extensively. However, the potential functional importance of sRANKL in critically ill or septic patients remained unknown. Therefore, we measured sRANKL serum concentrations in 303 critically ill patients, including 203 patients with sepsis and 100 with non-sepsis critical illness. Results were compared to 99 healthy controls. Strikingly, in critically ill patients sRANKL serum levels were significantly decreased at intensive care unit (ICU) admission (p = 0.011) without differences between sepsis and non-sepsis patients. Inline, sRANKL was correlated with markers of metabolic dysregulation, such as pre-existing diabetes and various adipokines (e.g., adiponectin, leptin receptor). Importantly, overall mortality of critically ill patients in a three-year follow-up was significantly associated with decreased sRANKL serum concentrations at ICU admission (p = 0.038). Therefore, our study suggests sRANKL as a biomarker in critically ill patients which is associated with poor prognosis and overall survival beyond ICU stay.
Salivary Exosome Proteomics and Bioinformatics Analysis in 7,12-Dimethylbenz[a]anthracene-Induced Oral Cancer with Radiation Therapy—A Syrian Golden Hamster Model
Authors: Wang Wen-Chen , Huang Ming-Yii , Chen Yuk-Kwan , Lan Wan-Chen , Shieh Tzong-Ming , Shih Yin-Hwa
Published: December 2021

Exosomes carry cellular proteins and contain molecules that can be potential biomarkers of diseases. This study used a Syrian golden hamster model of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral squamous cell carcinoma with radiation therapy to exclude the confounding factors that may affect outcomes in clinical studies, and re-examine the role of exosomes during tumorigenesis. We used data-dependent acquisition-based quantitative proteomics and bioinformatics analyses and found unique proteins present (desmocollin-2) or absent (Glucagon-cAMP-PKA-CREB pathway-related proteins) in the salivary exosomes of the pre-radiation DMBA-treated group (PreD). Comparing our data to other studies, salivary exosomes in the PreD group were found carrying proteins that the tumor mass does not express and lacking the proteins needed during tumorigenesis. Immunohistochemistry staining showed p53 expression but a negative apoptotic signal in the PreD tumor tissue. We thus suggest that inhibition of desmocollin-2 expression in tumor tissue may impede the activation of cell apoptosis. However, both the origin of the salivary exosomes and main role of the salivary exosome proteins should be clarified in future studies.
Evaluation of Anatomoradiological Findings on Trigeminal Neuralgia Patients Using Computed Tomography and Cone-Beam Computed Tomography
Authors: Aksoy Seçil , Sayın Şakul Arzu , Görür Durmuş İlker , Şakul Bayram Ufuk , Orhan Kaan
Published: December 2021

The study aimed to establish and evaluate anatomoradiological landmarks in trigeminal neuralgia patients using computed tomography (CT) and cone-beam CT. CT images of 40 trigeminal neuralgia (TN) and 40 healthy individuals were retrospectively analyzed and enrolled in the study. The width and length of the foramen rotundum (FR), foramen ovale (FO), foramen supraorbitale, and infraorbitale were measured. The distances between these foramen, between these foramen to the median plane, and between the superior orbital fissure, FO, and FR to clinoid processes were also measured bilaterally. Variations were evaluated according to groups. Significant differences were found for width and length of the foramen ovale, length of the foramen supraorbitale, and infraorbitale between TN and control subjects (p < 0.05). On both sides, FO gets narrower and the length of the infraorbital and supraorbital foramen shortens in the TN group. In most of the control patients, the plane which passes through the infraorbital and supraorbital foramen intersects with impression trigeminale; 70% on the right-side, and 67% in the left-side TN groups. This plane does not intersect with impression trigeminale and deviates in certain degrees. The determination of specific landmarks allows customization to individual patient anatomy and may help the surgeon achieve a more selective effect with a variety of percutaneous procedures in trigeminal neuralgia patients.
Urinary Biomarkers in Interstitial Cystitis/Bladder Pain Syndrome and Its Impact on Therapeutic Outcome
Authors: Lin Hung-Yu , Lu Jian-He , Chuang Shu-Mien , Chueh Kuang-Shun , Juan Tai-Jui , Liu Yi-Chang , Juan Yung-Shun
Published: December 2021

Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as a chronic bladder disorder with suprapubic pain (pelvic pain) and pressure and/or discomfort related to bladder filling accompanied by lower urinary tract symptoms, such as urinary frequency and urgency without urinary tract infection (UTI) lasting for at least 6 weeks. IC/BPS presents significant bladder pain and frequency urgency symptoms with unknown etiology, and it is without a widely accepted standard in diagnosis. Patients’ pathological features through cystoscopy and histologic features of bladder biopsy determine the presence or absence of Hunner lesions. IC/PBS is categorized into Hunner (ulcerative) type IC/BPS (HIC/BPS) or non-Hunner (nonulcerative) type IC/BPS (NHIC/BPS). The pathophysiology of IC/BPS is composed of multiple possible factors, such as chronic inflammation, autoimmune disorders, neurogenic hyperactivity, urothelial defects, abnormal angiogenesis, oxidative stress, and exogenous urine substances, which play a crucial role in the pathophysiology of IC/BPS. Abnormal expressions of several urine and serum specimens, including growth factor, methylhistamine, glycoprotein, chemokine and cytokines, might be useful as biomarkers for IC/BPS diagnosis. Further studies to identify the key molecules in IC/BPS will help to improve the efficacy of treatment and identify biomarkers of the disease. In this review, we discuss the potential medical therapy and assessment of therapeutic outcome with urinary biomarkers for IC/BPS.
Structural Analysis of SMYD3 Lysine Methyltransferase for the Development of Competitive and Specific Enzyme Inhibitors
Authors: Jarrell Dillon K. , Hassell Kelly N. , Alshiraihi Ilham , Crans Debbie C. , Brown Mark A.
Published: December 2021

Lysine methylation is among the key posttranslational modifications to histones that contribute to epigenetic regulation. SMYD3 is a lysine methyltransferase that is essential for the proliferation of a range of tumorigenic cells. The findings that SMYD3 is significantly upregulated in most colorectal carcinomas, hepatocellular carcinomas, and breast cell carcinomas support a model in which its aberrant expression modifies established patterns of gene expression, ultimately driving unrestrained proliferation. Herein, we dissect the unique structural features of SMYD3 relative to other SET enzymes, with an emphasis on the implications for selective design of therapeutics for the clinical management of cancer. Further, we illustrate the ability of inhibitors targeting the SET domain of SMYD3 to reduce the viability of colorectal and lung carcinoma cells.
GPS-Spoofing Attack Detection Technology for UAVs Based on Kullback–Leibler Divergence
Authors: Basan Elena , Basan Alexandr , Nekrasov Alexey , Fidge Colin , Sushkin Nikita , Peskova Olga
Published: December 2021

Here, we developed a method for detecting cyber security attacks aimed at spoofing the Global Positioning System (GPS) signal of an Unmanned Aerial Vehicle (UAV). Most methods for detecting UAV anomalies indicative of an attack use machine learning or other such methods that compare normal behavior with abnormal behavior. Such approaches require large amounts of data and significant “training” time to prepare and implement the system. Instead, we consider a new approach based on other mathematical methods for detecting UAV anomalies without the need to first collect a large amount of data and describe normal behavior patterns. Doing so can simplify the process of creating an anomaly detection system, which can further facilitate easier implementation of intrusion detection systems in UAVs. This article presents issues related to ensuring the information security of UAVs. Development of the GPS spoofing detection method for UAVs is then described, based on a preliminary study that made it possible to form a mathematical apparatus for solving the problem. We then explain the necessary analysis of parameters and methods of data normalization, and the analysis of the Kullback—Leibler divergence measure needed to detect anomalies in UAV systems.
Biographical Profiling of Nikola Tesla for the Creation of an Engaging Story
Authors: Hadzigeorgiou Yannis
Published: December 2021

This paper focuses on the potential of storytelling as a means of influencing students to become engaged with science and to choose a career in a STEM field. Given the role that leaders can play in motivating and influencing people and considering Nikola Tesla a leader in the fields of electrical engineering and science, the paper identifies Tesla’s leadership traits, as these emerge from his life story, that is, actual historical events regarding his life and his scientific/technological work. These leadership traits refer to (a) imaginative thinking and innovation, (b) persistence/perseverance, and (c) vision, and point to the need for empirical studies to document the effectiveness of the Nikola Tesla story to motivate and influence students. The significance of the Nikola Tesla story for science education is also discussed.
Regional Patterns of Access and Participation in Non-Formal Cultural Education in Germany
Authors: Fobel Lea , Kolleck Nina
Published: December 2021

(1) Background: The equality of life chances in Germany is often assessed along the lines of a west/east and urban/rural differentiation in which the latter usually perform worse. One currently popular proposal for addressing these inequalities is to strengthen cultural and arts education. The question arises to what extent regional characteristics genuinely influence participation opportunities and to what extent individual resources still play a decisive role. (2) Methods: Using descriptive analyses and multilevel logistic regression modelling, we investigate the distribution of and participation in non-formal cultural education amongst German youth. (3) Results: We find that differences are more complex than a simple west/east or urban/rural divides. Rather, cultural activities must be considered in terms of their character in order to assess the mechanisms at play. There seem to be differences in the dependency on district funding between very peripheral and very central districts that frame the cultural infrastructure. (4) Conclusions: Regional discrepancies are not uniformly distributed across different fields of education or infrastructure. Simplifying statements that classify peripheral regions the general losers can be refuted here. Simultaneously, more comprehensive data could yield significantly more results than we are currently able to produce.
Effects of Varying the Fin Width, Fin Height, Gate Dielectric Material, and Gate Length on the DC and RF Performance of a 14-nm SOI FinFET Structure
Authors: Boukortt Nour , Lenka Trupti , Patanè Salvatore , Crupi Giovanni
Published: December 2021

The FinFET architecture has attracted growing attention over the last two decades since its invention, owing to the good control of the gate electrode over the conductive channel leading to a high immunity from short-channel effects (SCEs). In order to contribute to the advancement of this rapidly expanding technology, a 3D 14-nm SOI n-FinFET is performed and calibrated to the experimental data from IBM by using Silvaco TCAD tools. The calibrated TCAD model is then investigated to analyze the impact of changing the fin width, fin height, gate dielectric material, and gate length on the DC and RF parameters. The achieved results allow gaining a better understanding and a deeper insight into the effects of varying the physical dimensions and materials on the device performance, thereby enabling the fabrication of a device tailored to the given constraints and requirements. After analyzing the optimal values from different changes, a new device configuration is proposed, which shows a good improvement in electrical characteristics.