bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovation speed under uncertainty and competition
Authors: Briest Gordon , Lukas Elmar , Mölls Sascha H. , Willershausen Timo
Published: July 2020

Innovation speed is widely considered to be a key factor for a firm's ability to maintain competitive advantage. Primarily, empirical evidence has found contradictory interdependencies regarding the role of innovation speed. The prevailing proposition of “the faster the better” has been challenged by results of empirical studies heavily depending on the methodological setup used. In contrast, we propose a model of the complete innovation process to study innovation speed under uncertainty and competition. We find that higher market uncertainty speeds up innovation and encourages firms to innovate incrementally. Strong competition tends to reduce innovation speed and encourages rather radical innovation.
Pattern recognition receptor‐mediated inflammation in diabetic vascular complications
Authors: Wang Xu , Antony Victor , Wang Yi , Wu Gaojun , Liang Guang
Published: July 2020

The innate immune system contains multiple classes of pattern recognition receptors (PRRs), which recognize pathogen‐associated molecular patterns (PAMPs) and danger‐associated molecular patterns (DAMPs) in the intracellular and extracellular space. Although PRRs are indispensable for the detection and clearance of invading pathogens, dysregulated PRR activation by extrinsic and intrinsic factors leads to inflammatory diseases. PRR‐mediated inflammation has been shown to play a pivotal role in the pathogenesis of diabetic vascular complications (DVCs), which are the leading causes of morbidity and mortality in diabetic patients. Upon sensing hyperglycemia‐generated DAMPs, PRRs activate intracellular signaling pathways leading to the production of proinflammatory cytokines and chemokines in various cells of the kidney, brain, eye, and heart. The resulting chronic, low‐grade inflammation contributes to DVCs. In this review, we summarize the role of PRRs in DVCs including diabetic nephropathy, neuropathy, retinopathy, and cardiomyopathy. We propose that targeting PRRs and associated signaling pathways may be beneficial for the management of DVCs.
Strong convergence of new iterative projection methods with regularization for solving monotone variational inequalities in Hilbert spaces
Authors: Van Hieu Dang , Dung Muu Le , Ngoc Duong Hoang , Huu Thai Buu
Published: July 2020

In this paper, we introduce two new numerical methods for solving a variational inequality problem involving a monotone and Lipschitz continuous operator in a Hilbert space. We describe how to incorporate a regularization term depending on a parameter in the projection method and then establish the strong convergence of the resulting iterative regularization projection methods. Unlike known hybrid methods, the strong convergence of the new methods comes from the regularization technique. The first method is designed to work in the case where the Lipschitz constant of cost operator is known, whereas the second one is more easily implemented without this requirement. The reason is because the second method has used a simple computable stepsize rule. The variable stepsizes are generated by the second method at each iteration and based on the previous iterates. These stepsizes are found with only one cheap computation without line‐search procedure. Several numerical experiments are implemented to show the computational effectiveness of the new methods over existing methods.
Head and neck multi‐organ auto‐segmentation on CT images aided by synthetic MRI
Authors: Liu Yingzi , Lei Yang , Fu Yabo , Wang Tonghe , Zhou Jun , Jiang Xiaojun , McDonald Mark , Beitler Jonathan J. , Curran Walter J. , Liu Tian , Yang Xiaofeng
Published: July 2020

Purpose

Because the manual contouring process is labor‐intensive and time‐consuming, segmentation of organs‐at‐risk (OARs) is a weak link in radiotherapy treatment planning process. Our goal was to develop a synthetic MR (sMR)‐aided dual pyramid network (DPN) for rapid and accurate head and neck multi‐organ segmentation in order to expedite the treatment planning process.

Methods

Forty‐five patients’ CT, MR, and manual contours pairs were included as our training dataset. Nineteen OARs were target organs to be segmented. The proposed sMR‐aided DPN method featured a deep attention strategy to effectively segment multiple organs. The performance of sMR‐aided DPN method was evaluated using five metrics, including Dice similarity coefficient (DSC), Hausdorff distance 95% (HD95), mean surface distance (MSD), residual mean square distance (RMSD), and volume difference. Our method was further validated using the 2015 head and neck challenge data.

Results

The contours generated by the proposed method closely resemble the ground truth manual contours, as evidenced by encouraging quantitative results in terms of DSC using the 2015 head and neck challenge data. Mean DSC values of 0.91 ± 0.02, 0.73 ± 0.11, 0.96 ± 0.01, 0.78 ± 0.09/0.78 ± 0.11, 0.88 ± 0.04/0.88 ± 0.06 and 0.86 ± 0.08/0.85 ± 0.1 were achieved for brain stem, chiasm, mandible, left/right optic nerve, left/right parotid, and left/right submandibular, respectively.

Conclusions

We demonstrated the feasibility of sMR‐aided DPN for head and neck multi‐organ delineation on CT images. Our method has shown superiority over the other methods on the 2015 head and neck challenge data results. The proposed method could significantly expedite the treatment planning process by rapidly segmenting multiple OARs.
Clinical validity of the PROMIS pediatric sleep short forms in children receiving treatment for cancer
Authors: Daniel Lauren C. , Gross J. Yael , Meltzer Lisa J. , Flannery Jamie L. , Forrest Christopher B. , Barakat Lamia P.
Published: July 2020

Background

Rates of sleep disturbances vary widely across pediatric cancer studies, partly due to differences in measurement tools. Patient‐reported outcomes measurement information system (PROMIS) offers a rigorously developed, well‐validated pair of pediatric sleep health instruments needed to advance sleep research and clinical practice in pediatric cancer. The current study evaluated the clinical validity of PROMIS pediatric sleep scales (sleep disturbances [SD] and sleep‐related impairment [SRI]) among children in active cancer treatment.

Procedure

Caregiver‐patient dyads were enrolled during cancer treatment in 2‐12 months after diagnosis: 45 children (ages 8‐17 years) and 102 caregivers of children (ages 5‐17 years) completed PROMIS SD and SRI 8‐item short form self‐report or caregiver‐proxy scales, and caregivers reported the prior week's cancer treatments and blood counts.

Results

Both scales demonstrated strong internal consistency reliability across reporters. SD and SRI were higher than the PROMIS general population calibration sample for caregivers and patients. Oncology caregivers reported lower SD and SRI than sleep clinic caregivers, but oncology patients were similar to sleep clinic patients. Convergent validity was evidenced through moderate correlations between scales by reporter and both scales being significantly higher in patients taking medications for sleep. There were no significant differences in SD or SRI by diagnostic group, receiving radiation, or having low blood counts.

Conclusion

The PROMIS SD and SRI short forms are promising measures for pediatric oncology, demonstrating strong internal consistency reliability and multiple indications of clinical validity. Although groups did not differ based on treatment variables, results suggest the need for universal screening for sleep problems during pediatric cancer treatment.
Synthesis of self‐assembled and porous nano titania‐graphene oxide hybrids for toughening the epoxy
Authors: Jayan Jitha S. , Saritha Appukuttan , Deeraj B.D.S. , Joseph Kuruvilla
Published: July 2020

Nano titania (nTiO2) aggregated graphene oxide (GO) hybrid nanostructures were successfully prepared by employing 3‐(Aminopropyl) triethoxysilane (APTES)‐modified nTiO2 as precursor material. The resulting self‐assembled core‐shell hybrid structure was observed to have hierarchical porous structure with nTiO2 forming the core and GO forming the shell in accordance with transmission electron micrographs. The mechanical properties of the hybrid composites were compared with that of individual GO and nTiO2 loaded systems and improved performance was observed. The incorporation of the hybrid filler improved the fracture toughness of epoxy composites by about 200%, which is indeed significant. Hence, this novel approach of employing self‐assembled APTES modified nTiO2 agglomerated GO hybrids as filler in epoxy was found to be beneficial in enhancing the toughness of epoxy.
Structure, properties, and applications of polyacrylonitrile/carbon nanotube (CNT) fibers at low CNT loading
Authors: Lu Mingxuan , Gulgunje Prabhakar V. , Arias‐Monje Pedro J. , Luo Jeffrey , Ramachandran Jyotsna , Sahoo Yudhisthira , Agarwal Sandip , Kumar Satish
Published: July 2020

Bi‐component, polyacrylonitrile (PAN)/carbon nanotube (CNT) fibers were processed, at different core‐sheath area ratios, by gel spinning. A percolated CNT network at 10 wt% CNT in the sheath enhanced electrical conductivity as compared to the neat PAN fiber, while PAN polymer in the core contributed to the good mechanical properties. Fibers with relatively thin sheath allowed overall CNT loading as low as 3.7 wt% to be made with good electrical conductivity, and PAN stabilization by Joule heating was demonstrated. Such fibers with combined good mechanical properties and electrical conductivity can also potentially be used for electrical heating of fabrics, for making smart textiles, and for electromagnetic interference shielding.
Very high VOC and FF of CdTe thin‐film solar cells with the applications of organo‐metallic halide perovskite thin film as a hole transport layer
Authors: Bhandari Khagendra P. , Alfadhili Fadhil K. , Bastola Ebin , Watthage Suneth C. , Song Zhaoning , Liyanage Geethika K. , Phillips Adam J. , Heben Michael J. , Ellingson Randy J.
Published: July 2020

We fabricate and characterize methylammonium lead halide perovskite film as a novel back contact to CdTe thin‐film solar cells. We apply ~0.75 μm perovskite film at the interface of CdCl2‐activated and Cu‐doped CdTe surface and complete the device with Au back contact. We use Cu/Au back contact as a reference to compare results with novel back contact. Our investigation shows that incorporation of thin layer of perovskite film before the back contact metal reduces back contact barrier effect and improves fill factor (FF) and open‐circuit voltage (VOC) of the solar cells. Our low temperature JV results prove that thin‐film perovskite is a very necessary component in CdTe solar cells to reduce back contact barrier, to minimize interface or surface recombination, to improve collection efficiencies, and to increase the efficiency of solar cells. Our best device shows 7% increase in VOC to 0.875 V and ~7% increase in FF with the highest FF of 81%, and solar cell's efficiency finally increases by 10% with the use of MAPb(I1‐xBrx)3 as an interface layer.
The definitive challenge of forming uncommon pseudo‐π···H–F and C···H–F hydrogen bonds on cyclic and cubic nonpolar hydrocarbons
Authors: Santos Gabriel Fateicha Neves , Carvalho Leila Cardoso , Oliveira Daniel Arley Santos , do Rego Danilo Guimarães , Bueno Mauro Alves , de Oliveira Boaz Galdino
Published: July 2020

Due to the high symmetry and low polarity of the cyclopropane (C3H6), cyclobutane (C4H8), prismane (C6H6), and cubane (C8H8), it is widely known that these structures unlikely act as proton receptors to form intermolecular interactions with monoprotic acids, such as the hydrogen fluoride. Although the C3H6···HF, C4H8···HF, C6H6···HF, and C8H8···HF are weakly bound complexes, in this current work, all of them were definitively certified on the basis of a theoretical analysis. In according with the structural parameters and spectroscopy modes appraised through the density‐functional theory calculations, the more accentuated perturbations are manifested in the hydrogen fluoride. The new hydrogen bond forms framed as pseudo‐π···H and C···H were unveiled through the calculations of the quantum theory of atoms in molecules and natural bond orbital. In this context, the knowledge about the nature of these hydrogen bonds is necessary, wherein it used the symmetry‐adapted perturbation theory for computing the contributions of the electrostatic, polarization, exchange, dispersion, and charge transfer terms. Lastly, the practical behavior of these hydrocarbons under the condition to form intermolecular interactions was examined by taking into account the solvent effect with calculations of the polarizable continuum model.
Targeting CPT1B as a potential therapeutic strategy in castration‐resistant and enzalutamide‐resistant prostate cancer
Authors: Abudurexiti Mierxiati , Zhu Wenkai , Wang Yuchen , Wang Jun , Xu Wenhao , Huang Yongqiang , Zhu Yao , Shi Guohai , Zhang Hailiang , Zhu Yiping , Shen Yijun , Dai Bo , Wan Fangning , Lin Guowen , Ye Dingwei
Published: July 2020

Background

Prostate cancer is characterized by aberrant lipid metabolism, including elevated fatty acid oxidation. Carnitine palmitoyltransferase 1B (CPT1B) catalyzes the rate‐limiting step of fatty acid oxidation. This study aimed to determine if CPT1B has a critical role in prostate cancer progression and to identify its regulatory mechanism.

Methods

CPT1B expression data from The Cancer Genome Atlas and Gene Expression Omnibus databases was compared with patient survival data. A tissue microarray was constructed with 60 samples of prostate cancer and immunohistochemically stained for CPT1B. Castration‐resistant prostate cancer (CRPC) cell lines 22RV1 and C4‐2 in which CPT1B expression had been stably knocked down were established; and cell proliferation, cell cycle distribution, and invasion were investigated by Cell Counting Kit‐8 (CCK‐8) and colony formation assays, flow cytometry, and Transwell assays, respectively. To examine the impact of androgen receptor (AR) inhibition on CPT1B expression, JASPAR CORE was searched to identify AR‐binding sites in CPT1B. Dual luciferase and ChIP assays were performed to confirm CPT1B activity and AR binding, respectively. Differentially expressed genes (DEGs) in prostate cancer underwent gene set enrichment analysis (GSEA). Enzalutamide‐resistant C4‐2 cells were generated and the mechanism of enzalutamide resistance and downstream signaling pathway changes of CPT1B to C4‐2 was explored through CCK‐8 test.

Results

CPT1B expression was upregulated in human prostate cancer compared with normal prostate tissue and was associated with poor disease‐free survival and overall survival. Silencing of CPT1B resulted in downregulated cell proliferation, reduced S‐phase distribution, and lower invasive ability, whereas the opposite was observed in CRPC cells overexpressing CPTB1. DEGS in prostate cancer were correlated with G‐protein–coupled receptor signaling, molecular transducer activity, and calcium ion binding. AR may regulate CPT1B expression and activity via specific binding sites, as confirmed by dual luciferase and ChIP assays. The CCK‐8 experiment demonstrated that CPT1B overexpression in C4‐2 cells did not significantly increase the ability of enzalutamide resistance. However, overexpression of CPT1B in C4‐2R cells significantly increased the enzalutamide resistance. Upregulation of CPT1B expression increased AKT expression and phosphorylation.

Conclusions

CPT1B is upregulated in prostate cancer and is correlated with poor prognosis, indicating its potential as a biomarker. AR inhibits the transcription of CPT1B. In the CRPC cell line, overexpression of CPT1B alone cannot promote enzalutamide resistance, but in the drug‐resistant line C4‐2R, overexpression of CPT1B can promote the resistance of C4‐2R to enzalutamide.
Integration of Dielectric and Ferroelectric Hafnium Aluminum Oxides for Thin‐Film Transistor Applications
Authors: Hsu Hsiao-Hsuan , Lee Sheng , Liu Hsiu-Ming
Published: July 2020

Herein, the integration of dielectric and ferroelectric HfAlOx within a one‐transistor and one‐capacitor thin‐film transistor (TFT)‐based device structure is successfully demonstrated. It is found that the origin of gate stress for enhancing ferroelectricity is mainly ascribed to nonlinear thermal stress distribution, and the ferroelectricity of HfAlOx is further improved by nitrogen plasma treatment without sacrificing leakage current during post metal annealing. Notably, the p‐type SnO TFT in series with a ferroelectric HfAlOx capacitor with nitrogen plasma treatment achieves an almost 43% improvement on threshold voltage shift (5.45 V) at a low operating voltage of 3 V. Therefore, the ferroelectric nitridation treatment not only strengthens the ferroelectric domain switching of HfAlOx but also improves capacitance matching with the HfAlOx dielectric layer of p‐type SnO TFT.
A nonparametric double generally weighted moving average signed‐rank control chart for monitoring process location
Authors: Alevizakos Vasileios , Koukouvinos Christos , Chatterjee Kashinath
Published: July 2020

Most control charts have been developed based on the actual distribution of the quality characteristic of interest. However, in many applications, there is a lack of knowledge about the process distribution. Therefore, in recent years, nonparametric (or distribution‐free) control charts have been introduced for monitoring the process location or scale parameter. In this article, a nonparametric double generally weighted moving average control chart based on the signed‐rank statistic (referred as DGWMA‐SR chart) is proposed for monitoring the location parameter. We provide the exact approach to compute the run‐length distribution, and through an extensive simulation study, we compare the performance of the proposed chart with existing nonparametric charts, such as the exponentially weighted moving average signed‐rank (EWMA‐SR), the generally weighted moving average signed‐rank (GWMA‐SR), the double exponentially weighted moving average signed‐rank (DEWMA‐SR), and the double generally weighted moving average sign (DGWMA‐SN) charts, as well as the parametric DGWMA‐
chart for subgroup averages. The simulation results show that the DGWMA‐SR chart (with suitable parameters) is more sensitive than the other competing charts for small shifts in the location parameter and performs as well as the other nonparametric charts for larger shifts. Finally, two examples are given to illustrate the application of the proposed chart.
Bioactive activities and chemical profile characterization using paper spray mass spectrometry of extracts of Eriobotrya japonica Lindl. leaves
Authors: Silva Viviane D.M. , Macedo Maria Clara C. , dos Santos Amanda N. , Silva Mauro R. , Augusti Rodinei , Lacerda Inayara Cristina A. , Melo Júlio Onésio F. , Fante Camila A.
Published: July 2020

Rationale

The loquat (Eriobotrya japonica Lindl.) is a fruit tree that has been used in Chinese medicine for thousands of years for the treatment of various diseases. The loquat leaf extracts contain several bioactive compounds with antioxidant and antimicrobial properties, and identification of these substances using quick and simple methods has been an analytical trend.

Methods

The influence of dehydration of loquat leaves (without drying, at 40°C, and at 60°C), the type of solvent (ethanol and methanol), and the method of extraction (shaking and ultrasound) on obtaining extracts containing phenolic compounds and substances with antioxidant and antimicrobial properties was evaluated. The chemical constituents of an extract were identified using paper spray mass spectrometry (PS‐MS).

Results

The extract obtained from the dehydrated leaves at 40°C presented the best results. The extracts obtained from these leaves and with ethanol had the highest values of total phenolics and antioxidant activities, but the methanolic extract subjected to ultrasound had the highest levels of chlorogenic, caffeic, and ellagic acids. All extracts evaluated inhibited the growth of Staphylococcus aureus. Using the PS‐MS technique, it was possible to identify the presence of 49 substances such as organic acids, phenolic acids, flavonoids, sugars, quinones, and terpenes.

Conclusions

In general, extracts of dehydrated leaves at 40°C and extracted with ethanol using ultrasound can be considered a good source of bioactive compounds with potential applications as functional ingredients or additives in the food and pharmaceutical industries. PS‐MS was demonstrated to be a simple and ultrafast technique to obtain the chemical profile of the loquat leaf extract.
Optimum seismic design of steel framed‐tube and tube‐in‐tube tall buildings
Authors: Sarcheshmehpour Mohammad , Estekanchi Homayoon E. , Moosavian Hashem
Published: July 2020

The relatively large number of structural elements and the variety of design code requirements complicate the design process of tall buildings. This process is exacerbated when the target is to obtain the seismic code‐compliant optimal design with minimum weight. The present paper aims at providing a practical methodology for the optimal design of steel tall building structures considering the constraints imposed by typical building codes. The applicability of the proposed approach is demonstrated through the determination of the optimal seismic design for 20‐, 40‐, and 60‐story buildings with a framed tube as well as a tube‐in‐tube system. Such a design gives rise to a basis for the fair comparison of the behavior of the framed tube with that of the tube‐in‐tube system under applied loads. The optimal weight of the buildings with the tube‐in‐tube system turns out to be slightly less than that of the buildings with the conventional framed‐tube system.
Bassoon inhibits proteasome activity via interaction with PSMB4
Authors: Montenegro-Venegas Carolina , Fienko Sandra , Anni Daniela , Pina-Fernández Eneko , Frischknecht Renato , Fejtova Anna
Published: July 2020

Proteasomes are protein complexes that mediate controlled degradation of damaged or unneeded cellular proteins. In neurons, proteasome regulates synaptic function and its dysfunction has been linked to neurodegeneration and neuronal cell death. However, endogenous mechanisms controlling proteasomal activity are insufficiently understood. Here, we describe a novel interaction between presynaptic scaffolding protein bassoon and PSMB4, a β subunit of the 20S core proteasome. Expression of bassoon fragments that interact with PSMB4 in cell lines or in primary neurons attenuates all endopeptidase activities of cellular proteasome and induces accumulation of several classes of ubiquitinated and non-ubiquitinated substrates of the proteasome. Importantly, these effects are distinct from the previously reported impact of bassoon on ubiquitination and autophagy and might rely on a steric interference with the assembly of the 20S proteasome core. In line with a negative regulatory role of bassoon on endogenous proteasome we found increased proteasomal activity in the synaptic fractions prepared from brains of bassoon knock-out mice. Finally, increased activity of proteasome and lower expression levels of synaptic substrates of proteasome could be largely normalized upon expression of PSMB4-interacting fragments of bassoon in neurons derived from bassoon deficient mice. Collectively, we propose that bassoon interacts directly with proteasome to control its activity at presynapse and thereby it contributes to a compartment-specific regulation of neuronal protein homeostasis. These findings provide a mechanistic explanation for the recently described link of bassoon to human diseases associated with pathological protein aggregation.

Graphic Abstract

Presynaptic cytomatrix protein bassoon (Bsn) interacts with PSMB4, the β7 subunit of 20S core proteasome, via three independent interaction interfaces. Bsn inhibits proteasomal proteolytic activity and degradation of different classes of proteasomal substrates presumably due to steric interference with the assembly of 20S core of proteasome. Upon Bsn deletion in neurons, presynaptic substrates of the proteasome are depleted, which can be reversed upon expression of PSMB4-interacting interfaces of Bsn. Taken together, bsn controls the degree of proteasome degradation within the presynaptic compartment and thus, contributes to the regulation of synaptic proteome
Akustische Qualität und Stadtgesundheit – Mehr als nur Lärm und Stille
Authors: Moebus Susanne , Gruehn Dietwald , Poppen Jonas , Sutcliffe Robynne , Haselhoff Timo , Lawrence Bryce
Published: July 2020

Neue Ansätze in der Stadtentwicklung werden gefordert, um Städte in nachhaltige Orte zu transformieren. Das erfordert u. a. eine Verdichtung der Städte, die kaum denkbar ist ohne eine Zunahme der Geräuschentwicklung – meist in Form von Lärm. Um eine Akzeptanz für die Verdichtung zu erreichen, sind qualitätsvolle, gesundheitsförderliche akustische städtische Räume erforderlich. Hierfür bedarf es Ansätze, die über reine Lärmminderungsmaßnahmen hinausgehen. Ausgehend von der Frage: „Was hält gesund?“, ist eine Perspektive, die auf eine gesundheitsförderliche städtische Klangqualität bzw. auf eine positiv bewertete akustische Umgebung zielt, erforderlich. Geräusche können als gestaltbare Qualität in urbanen Räumen als eine wichtige Ressource für eine gesundheitsförderliche Stadt verstanden werden. Hierfür werden über die schallpegelbasierten Indizes hinaus weitere Metriken benötigt, die eine gute urbane Klangqualität indizieren können. Wissen, Forschung und Anwendung zu urbaner akustischer Qualität, insbesondere mit Blick auf Gesundheit, befinden sich noch in den Anfängen. Für Urban Public Health schlagen wir eine Perspektiverweiterung durch die Verknüpfung und systematische Anwendung von zwei verschiedenen Soundscape-Ansätzen vor. Der vorliegende Beitrag gibt einen kurzen Überblick zu den Begriffen „Lärm“ und „Geräusche“, stellt zwei Ansätze der Soundscape-Forschung vor und legt anschließend Ziele und Methodik des Pilotprojektes SALVE („akustische Qualität und Gesundheit in urbanen Räumen“) zum Thema akustische Qualität in urbanen Räumen dar. Insgesamt wird ein Einblick in das neue Forschungs- und Praxisfeld von urbaner Klangqualität, Soundscapes und Stadtgesundheit gegeben.
Functional modelling of complex multi-disciplinary systems using the enhanced sequence diagram
Authors: Yildirim Unal , Campean Felician
Published: July 2020

This paper introduces an Enhanced Sequence Diagram (ESD) as the basis for a structured framework for the functional analysis of complex multidisciplinary systems. The ESD extends the conventional sequence diagrams (SD) by introducing a rigorous functional flow-based modelling schemata to provide an enhanced basis for model-based functional requirements and architecture analysis in the early systems design stages. The proposed ESD heuristics include the representation of transactional and transformative functions required to deliver the use case sequence, and fork and join nodes to facilitate analysis of combining and bifurcating operations on flows. A case study of a personal mobility device is used to illustrate the deployment of the ESD methodology in relation to three common product development scenarios: (i) reverse engineering, (ii) the introduction of a specific technology to an existent system; and (iii) the introduction of a new feature as user-centric innovation for an existing system, at a logical design level, without reference to any solution. The case study analysis provides further insights into the effectiveness of the ESD to support function modelling and functional requirements capture, and architecture development. The significance of this paper is that it establishes a rigorous ESD-based functional analysis methodology to guide the practitioner with its deployment, facilitating its impact to both the engineering design and systems engineering communities, as well as the design practice in the industry.
Catalytically-active inclusion bodies for biotechnology—general concepts, optimization, and application
Authors: Jäger Vera D. , Lamm Robin , Küsters Kira , Ölçücü Gizem , Oldiges Marco , Jaeger Karl-Erich , Büchs Jochen , Krauss Ulrich
Published: July 2020

Bacterial inclusion bodies (IBs) have long been considered as inactive, unfolded waste material produced by heterologous overexpression of recombinant genes. In industrial applications, they are occasionally used as an alternative in cases where a protein cannot be expressed in soluble form and in high enough amounts. Then, however, refolding approaches are needed to transform inactive IBs into active soluble protein. While anecdotal reports about IBs themselves showing catalytic functionality/activity (CatIB) are found throughout literature, only recently, the use of protein engineering methods has facilitated the on-demand production of CatIBs. CatIB formation is induced usually by fusing short peptide tags or aggregation-inducing protein domains to a target protein. The resulting proteinaceous particles formed by heterologous expression of the respective genes can be regarded as a biologically produced bionanomaterial or, if enzymes are used as target protein, carrier-free enzyme immobilizates. In the present contribution, we review general concepts important for CatIB production, processing, and application.

Key points

• Catalytically active inclusion bodies (CatIBs) are promising bionanomaterials.

• Potential applications in biocatalysis, synthetic chemistry, and biotechnology.

• CatIB formation represents a generic approach for enzyme immobilization.

• CatIB formation efficiency depends on construct design and expression conditions.
Predictive Value of the Age‐Adjusted Charlson Comorbidity Index for Outcomes After Hepatic Resection of Hepatocellular Carcinoma
Authors: Shinkawa Hiroji , Tanaka Shogo , Takemura Shigekazu , Amano Ryosuke , Kimura Kenjiro , Nishioka Takayoshi , Miyazaki Toru , Kubo Shoji
Published: July 2020

Background

This study aimed to evaluate the impact of the age‐adjusted Charlson comorbidity index (ACCI) on outcomes after hepatic resection for hepatocellular carcinoma (HCC).

Methods

We assessed 763 patients who underwent hepatic resection for HCC. The ACCI scores were categorized as follows: ACCI ≤ 5, ACCI = 6, and ACCI ≥ 7.

Results

A multivariate analysis showed that the odds ratios for postoperative complications in ACCI = 6 and ACCI ≥ 7 groups, with reference to ACCI ≤ 5 group, were 0.71 (p = 0.41) and 4.15 (p < 0.001), respectively. The hazard ratios for overall survival of ACCI = 6 and ACCI ≥ 7 groups, with reference to ACCI ≤ 5 group, were 1.52 (p = 0.023) and 2.45 (p < 0.001), respectively. The distribution of deaths due to HCC‐related, liver‐related, and other causes was 68.2%, 11.8%, and 20% in ACCI ≤ 5 group, 47.2%, 13.9%, and 38.9% in ACCI = 6 group, and 27.3%, 9.1%, and 63.6% in ACCI ≥ 7 group (p = 0.053; ACCI ≤ 5 vs. = 6, p = 0.19; ACCI = 6 vs. ≥ 7, p < 0.001; ACCI ≤ 5 vs. ≥ 7). In terms of the treatment for HCC recurrence in ACCI ≤ 5, ACCI = 6, and ACCI ≥ 7 groups, adaptation rate of surgical resection was 20.1%, 7.3%, and 11.1% and the rate of palliative therapy was 4.3%, 12.2%, and 22.2%, respectively.

Conclusions

The ACCI predicted the short‐term and long‐term outcomes after hepatic resection of HCC. These findings will help physicians establish a treatment strategy for HCC patients with comorbidities.
Molecular detection of Theileria species and Babesia caballi from horses in Nigeria
Authors: Mshelia Philip W. , Kappmeyer Lowell , Johnson Wendell C. , Kudi Caleb A. , Oluyinka Okubanjo O. , Balogun Emmanuel O. , Richard Edeh E. , Onoja Emmanuel , Sears Kelly P. , Ueti Massaro W.
Published: July 2020

Equine piroplasmosis (EP) is an infectious, tick-borne disease caused by the hemoprotozoan parasites, Theileria equi, Babesia caballi, and a recently reported new species, T. haneyi. Infections by these apicomplexan parasites limit performance and cause economic losses for the horse industry. Equine piroplasmosis is widespread in the northern regions of Nigeria, where an increasing portion of the animal population is composed of horses. This disease has remained epidemiologically challenging, especially as the movement of horses increases across Nigeria. In this study, blood samples from 300 horses were collected in three states of northwestern Nigeria. The presence of piroplasms was screened by nested PCR targeting 18S rDNA and positive samples were analyzed using species-specific-nested PCR-targeting genes including ema1 (T. equi), rap1 (B. caballi), and a gene coding a protein of unknown function (T. haneyi). Species-specific-nPCR results demonstrated that the prevalence of T. equi was 13.0% (39/300), B. caballi was 3.3% (10/300) and T. haneyi was 2.7% (8/300). Mixed infections with T. equi and B. caballi was 2.7% (8/300) while T. equi, B. caballi, and T. haneyi multiple infection prevalence was 0.6% (2/300). We used 18S rDNA sequences to determine close relationships between T. equi by phylogenetic analysis and demonstrated that among 57 sequences of Theileria parasites, 28 samples belonged to clade A (49%), 13 samples were found to be clade C (22%), and 16 were clade D (28%). These results demonstrate the genetic diversity of T. equi circulating in horses from Nigeria.
Live Imaging of embryogenic structures in Brassica napus microspore embryo cultures highlights the developmental plasticity of induced totipotent cells
Authors: Corral-Martínez Patricia , Siemons Charlotte , Horstman Anneke , Angenent Gerco C. , de Ruijter Norbert , Boutilier Kim
Published: July 2020

Key message

In vitro embryo development is highly plastic; embryo cell fate can be re-established in tissue culture through different pathways.

In most angiosperms, embryo development from the single-celled zygote follows a defined pattern of cell divisions in which apical (embryo proper) and basal (root and suspensor) cell fates are established within the first cell divisions. By contrast, embryos that are induced in vitro in the absence of fertilization show a less regular initial cell division pattern yet develop into histodifferentiated embryos that can be converted into seedlings. We used the Brassica napus microspore embryogenesis system, in which the male gametophyte is reprogrammed in vitro to form haploid embryos, to identify the developmental fates of the different types of embryogenic structures found in culture. Using time-lapse imaging of LEAFY COTYLEDON1-expressing cells, we show that embryogenic cell clusters with very different morphologies are able to form haploid embryos. The timing of surrounding pollen wall (exine) rupture is a major determinant of cell fate in these clusters, with early exine rupture leading to the formation of suspensor-bearing embryos and late rupture to suspensorless embryos. In addition, we show that embryogenic callus, which develops into suspensor-bearing embryos, initially expresses transcripts associated with both basal- and apical-embryo cell fates, suggesting that these two cell fates are fixed later in development. This study reveals the inherent plasticity of in vitro embryo development and identifies new pathways by which embryo cell fate can be established.
The IDEAL framework in neurosurgery: a bibliometric analysis
Authors: Ota Helen C. U. , Smith Brandon G. , Alamri Alexander , Robertson Faith C. , Marcus Hani , Hirst Allison , Broekman Marike , Hutchinson Peter , McCulloch Peter , Kolias Angelos
Published: July 2020

Background

The Idea, Development, Exploration, Assessment and Long-term study (IDEAL) framework was created to provide a structured way for assessing and evaluating novel surgical techniques and devices.

Objectives

The aim of this paper was to investigate the utilization of the IDEAL framework within neurosurgery, and to identify factors influencing implementation.

Methods

A bibliometric analysis of the 7 key IDEAL papers on Scopus, PubMed, Embase, Web of Science, and Google Scholar databases (2009–2019) was performed. A second journal-specific search then identified additional papers citing the IDEAL framework. Publications identified were screened by two independent reviewers to select neurosurgery-specific articles.

Results

The citation search identified 1336 articles. The journal search identified another 16 articles. Following deduplication and review, 51 relevant articles remained; 14 primary papers (27%) and 37 secondary papers (73%). Of the primary papers, 5 (36%) papers applied the IDEAL framework to their research correctly; two were aligned to the pre-IDEAL stage, one to the Idea and Development stages, and two to the Exploration stage. Of the secondary papers, 21 (57%) explicitly discussed the IDEAL framework. Eighteen (86%) of these were supportive of implementing the framework, while one was not, and two were neutral.

Conclusion

The adoption of the IDEAL framework in neurosurgery has been slow, particularly for early-stage neurosurgical techniques and inventions. However, the largely positive reviews in secondary literature suggest potential for increased use that may be achieved with education and publicity.
Do males and females respond differently to ocean acidification? An experimental study with the sea urchin Paracentrotus lividus
Authors: Marčeta Tihana , Matozzo Valerio , Alban Silvia , Badocco Denis , Pastore Paolo , Marin Maria Gabriella
Published: July 2020

Seawater pH lowering, known as ocean acidification, is considered among the major threats to marine environment. In this study, post-spawning adults of the sea urchin Paracentrotus lividus were maintained at three pH values (8.0, 7.7, 7.4) for 60 days. Physiological, biochemical, cellular, behavioural and reproductive responses were evaluated in males and females. Significant differences between sexes were observed, with higher ammonia excretion and lower catalase activity in males. Respiration rate (after 21 days), catalase activity in gonads and total coelomocyte count showed the same increasing trend in males and females under low pH. Ammonia excretion, gonadosomatic index and lysozyme activity exhibited opposite responses to low pH, with an increasing trend in males and decreasing in females. Results demonstrated that exposure to low pH could result in different response strategies of male and female sea urchins at a physiological, biochemical and immunological level. Reduced female gonadosomatic index under low pH suggested decreased energy investment in reproduction.
Revealing the Subsurface Basal 〈a〉 Dislocation Activity in Magnesium Through Lattice Rotation Analysis
Authors: Zhou Bijin , Wang Leyun , Liu Wenjun , Zeng Xiaoqin , Li Yanjun
Published: July 2020

A method was proposed in this study to reveal the subsurface basal dislocation activity in Mg-Y alloy and determine the corresponding Burgers vector. This is achieved by correlating the slip directions of dislocations to the lattice rotation represented by the {0001} pole figure. The identified basal slip system by this approach was verified by micro-Laue diffraction. This method can be applied as a complementary method to the conventional slip trace analysis to study the dislocation behavior of Mg alloys.
Rückfallbegünstigende und rückfallprotektive Faktoren nach der Entlassung aus dem Maßregelvollzug
Authors: Walde Peggy , Lungwitz Vivien
Published: July 2020

Im vorliegenden systematischen Review werden Faktoren zusammengetragen, welche den Erfolg der Legalbewährung bei entlassenen Patienten des Maßregelvollzugs (§§ 63 und 64 StGB) positiv oder negativ beeinflussen können. Als Ergebnis einer Literaturrecherche konnten 7 häufig untersuchte Bereiche identifiziert werden: Wohnumgebung, Erwerbstätigkeit, Familie/Partnerschaft, Freizeit/soziale Kontakte, Substanzkonsum, Nachsorge und psychologische Variablen. Aus den Ergebnissen wurden, wo möglich, Daten zur Quantifizierung von Größe und Richtung der Effekte berechnet. Diese zeigen für Patienten des psychiatrischen Maßregelvollzugs ein erhöhtes Rückfallrisiko bei Substanzmissbrauch und häufigem Wechsel von Wohnort und Arbeitsplatz. Protektiv wirken dagegen ein psychisch stabiler Zustand und ein zumindest während der ersten Zeit nach der Entlassung institutionalisiertes Wohnumfeld. Für Patienten, die nach § 64 StGB untergebracht sind, können keine eindeutigen Aussagen getroffen werden. Auch hier scheint jedoch erneuter Suchtmittelkonsum das Risiko für Rückfälle zu erhöhen.
Social Robots to Test Flexibility of Human Social Cognition
Authors: Wykowska Agnieszka
Published: July 2020

As the field of social robotics has been dynamically growing and expanding over various areas of research and application, in which robots can be of assistance and companionship for humans, this paper offers a different perspective on a role that social robots can also play, namely the role of informing us about flexibility of human mechanisms of social cognition. The paper focuses on studies in which robots have been used as a new type of “stimuli” in psychological experiments to examine whether similar mechanisms of social cognition would be activated in interaction with a robot, as would be elicited in interaction with another human. Analysing studies in which a direct comparison has been made between a robot and a human agent, the paper examines whether for robot agents, the brain re-uses the same mechanisms that have been developed for interaction with other humans in terms of perception, action representation, attention and higher-order social cognition. Based on this analysis, the paper concludes that the human socio-cognitive mechanisms, in adult brains, are sufficiently flexible to be re-used for robotic agents, at least for those that have some level of resemblance to humans.
Hermitian Toeplitz determinants of the second and third-order for classes of close-to-star functions
Authors: Jastrzȩbski Piotr , Kowalczyk Bogumiła , Kwon Oh Sang , Lecko Adam , Sim Young Jae
Published: July 2020

For some subclasses of close-to-star functions the sharp upper and lower bounds of the second and third-order Hermitian Toeplitz determinants are computed.
Intensive Versus Extensive Events? Insights from Cumulative Flood-Induced Mortality Over the Globe, 1976–2016
Authors: Chen Bo , Shi Fanya , Lin Tingting , Shi Peijun , Zheng Jing
Published: July 2020

More attention has been paid to the cost of intensive but sporadic floods than the cost of extensive but frequent events. To examine the impacts of intensive versus extensive events, we investigated the loss structure of global flood-induced mortality by using the cumulative loss ratio, marginal benefit chart, and cumulative loss plot. Drawing on the flood-induced mortality data for four decades (1976–2016) from the international disaster database EM-DAT, we defined the levels of flood loss according to the frequency of flood-induced deaths, and calculated the cumulative mortality and the marginal benefits of flood loss prevention practices at different levels. Our analysis showed that for the world’s leading 30 countries with large flood-induced mortality and different levels of development: (1) 70% of them have the cumulative deaths from extensive floods exceeding half of those caused by intensive floods in the study’s four data decades; and (2) 80% of them tend to gain less marginal benefit with increasing levels of flood prevention, with their marginal benefits peaking at loss prevention levels of 2-year or 5-year flood-induced mortality. These results indicate that, in the long run, the cumulative deaths of extensive floods are comparable to that of intensive events, and prevention of loss from extensive events can be an efficient way to reduce the total loss. For flood risk management under conditions of climate change, extensive loss events deserve more consideration.
Megaphones hiding in trees: civic instruction via mediated soundscapes in places of natural beauty in China
Authors: Tan Shzr Ee
Published: July 2020

Places of ‘scenic beauty’ in China—national parks, panda enclosures, holy mountains, private gardens—have been sites where encounters with nature have been constructed through idealisations of particular ecologies. Often, in these environments, the sonic design of space predicates as much on ‘organic’ elements as on deliberately-engineered and broadcast ‘artificial’ sounds. Loudspeakers are hidden in trees and rocks. Broadcasting ambient sounds throughout the course of the day, they send signals ranging from Chinese classical music to spoken descriptions of local objects of interest, to exhortations to walk in an orderly fashion, to religions chants. Sometimes, the broadcasts are presented in overt articulations in invocation of public service announcements or tourist information posts. Based on multi-sited fieldwork in Northern, Eastern and Southern China, this paper considers such mediated soundscapes along four axes of analysis. First, I contextualise such sonic ‘atmospheres’ within surveillance culture in China and civic instruction through public address. Second, I examine them within a longer, well-known history of Taoist philosophy that positions man in relationship to the cosmos through a perspective of ‘artifice’ embedded in oppositional co-existence with ‘nature’. Third, I explore these articulations as multisensorial experiences found in ecotouristic brands. Finally, I critique these sonic mediations in interaction with perceived ‘natural’ sounds within broader theorizations of ecomusicology developed by Guy (Ethnomusicology 53(2):218–248, 2009) and Rees (Ethnomusicology 60(1):53–88, 2016), coming to conclusions on national vs local acoustic ecologies of the ‘natural’ Chinese world.
Pandemic pushes polarisation: the Corona crisis and macroeconomic divergence in the Eurozone
Authors: Gräbner Claudius , Heimberger Philipp , Kapeller Jakob
Published: July 2020

This paper discusses the uneven consequences of the macroeconomic fallout from the Coronavirus and related economic policy responses against the background of an analysis of longer-term macroeconomic divergence in the Eurozone. We show that the macroeconomic impact of the Corona crisis is estimated to be more severe in Southern Eurozone countries than in Northern Eurozone countries, which further reinforces the tendency of an increasing economic polarisation. This polarisation process can be traced back to existing differences in production structures and uneven vulnerabilities of the underlying growth models. As a consequence, any policy response to the Corona crisis that does not take the deeper problems of structural polarisation into account will suffer from limited impact in the medium to long run.
In-silico Molecular Docking and ADME/Pharmacokinetic Prediction Studies of Some Novel Carboxamide Derivatives as Anti-tubercular Agents
Authors: Abdullahi Mustapha , Adeniji Shola Elijah
Published: July 2020

Molecular docking simulation of thirty-five (35) molecules ofN-(2-phenoxy)ethyl imidazo[1,2-a]pyridine-3-carboxamide (IPA) withMycobacterium tuberculosistarget (DNA gyrase) was carried out so as to evaluate their theoretical binding affinities. The chemical structure of the molecules was accurately drawn using ChemDraw Ultra software, then optimized at density functional theory (DFT) using Becke’s three-parameter Lee–Yang–Parr hybrid functional (B3LYP/6-311**) basis set in a vacuum of Spartan 14 software. Subsequently, the docking operation was carried out using PyRx virtual screening software. Molecule 35 (M35) with the highest binding affinity of − 7.2 kcal/mol was selected as the lead molecule for structural modification which led to the development of four (4) newly hypothetical molecules D1, D2, D3 and D4. In addition, the D4 molecule with the highest binding affinity value of − 9.4 kcal/mol formed more H-bond interactions signifying better orientation of the ligand in the binding site compared to M35 and isoniazid standard drug. In-silico ADME and drug-likeness prediction of the molecules showed good pharmacokinetic properties having high gastrointestinal absorption, orally bioavailable, and less toxic. The outcome of the present research strengthens the relevance of these compounds as promising lead candidates for the treatment of multidrug-resistant tuberculosis which could help the medicinal chemists and pharmaceutical professionals in further designing and synthesis of more potent drug candidates. Moreover, the research also encouraged the in vivo and in vitro evaluation study for the proposed designed compounds to validate the computational findings.