bluuebunny/crossref_metadata_2025 huggingface dataset:
A hybrid genetic local and global search algorithm for solving no-wait flow shop problem with bi criteria
Authors: Keskin Kenan , Engin Orhan
Published: May 2021

This paper addresses them-machine no-wait Flow Shop Scheduling with Setup Times (NW-FSSWST). Two performance measures: total flow time and makespan are considered. The objective is to find a sequence that minimizing total flow time ($$\sum C_{j}$$∑Cj) and makespan ($$C_{j}$$Cj) simultaneously. A Hybrid Genetic Local and Global Search Algorithm (HGLGSA) is proposed to solve the NW-FSSWST for two performance criteria. The hybrid genetic algorithm is constructed by insert-search and self-repair algorithm with self-repair function. The proposed HGLGSA is tested on 192 benchmark problems of NW-FSSWST in the literature. A full factorial experimental design is made for determined the best parameter sets that improve the performance of the proposed algorithm. The computational results are compared with the benchmark solutions from the literature. The experimental results demonstrate the effectiveness and efficiency of the proposed HGLGSA for solving NW-FSSWST.
Enhancement of out-of-plane mechanical properties of carbon fiber reinforced epoxy resin composite by incorporating the multi-walled carbon nanotubes
Authors: Mirsalehi Seyed Ali , Youzbashi Amir Ali , Sazgar Amjad
Published: May 2021

In this study, epoxy hybrid nanocomposites reinforced by carbon fibers (CFs) were fabricated by a filament winding. To improve out-of-plane (transverse) mechanical properties, 0.5 and 1.0 Wt.% multi-walled carbon nanotubes (MWCNTs) were embedded into epoxy/CF composites. The MWCNTs were well dispersed into the epoxy resin without using any additives. The transverse mechanical properties of epoxy/MWCNT/CF hybrid nanocomposites were evaluated by the tensile test in the vertical direction to the CFs (90º tensile) and flexural tests. The fracture surfaces of composites were studied by scanning electron microscopy (SEM). The SEM observations showed that the bridging of the MWCNTs is one of the mechanisms of transverse mechanical properties enhancement in the epoxy/MWCNT/CF composites. The results of the 90º tensile test proved that the tensile strength and elongation at break of nanocomposite with 1.0 Wt.% MWCNTs improved up to 53% and 50% in comparison with epoxy/CF laminate composite, respectively. Furthermore, the flexural strength, secant modulus, and elongation of epoxy/1.0 Wt.% MWCNT/CF hybrid nanocomposite increased 15%, 7%, and 9% compared to epoxy/CF laminate composite, respectively.
Sphingolipid profiles and their relationship with inflammatory factors in asthmatic patients of different sexes
Authors: Song Zhu , Yan Wei , Abulikemu Mairipaiti , Wang Juan , Xing Yan , Zhou Qingtao , Ma Shaohua , Chang Chun
Published: May 2021

Background

Asthma is a heterogeneous disease with distinct prevalence and manifestation between sexes. This study was to identify sex‐specific features of asthma via metabolomic analysis of sphingolipids.

Methods

Forty‐two asthma patients (27 women and 15 men) admitted to the Peking University Third Hospital from January 2015 to December 2015 were enrolled. Peripheral venous blood was collected for metabolomic analysis by targeted liquid chromatography‐mass spectrometry. Sex hormones(estradiol, progesterone, testosterone, and androstenedione) and multiple inflammatory factors (periostin, leptin, IgE, IL‐4, IL‐5, IL‐10, IL‐13, IL‐17A, and IFN‐γ) were also assessed. The eosinophil percentage in induced sputum was also detected. All these data were applied to comparative analysis between sexes.

Results

Testosterone was negatively related to periostin (ρ = −0.420, P = 0.009) and IL‐5 (ρ = −0.540, P = 0.012), while estradiol was positively related to the blood eosinophil percentage (ρ = 0.384, P = 0.025). Among the eighteen species of sphingolipids detected in the 42 patients, five ceramide (Cer) species (Cer16:0, Cer:20:0, Cer22:0, Cer24:0, and Cer26:0) and one sphingomyelin (SM) species (SM38:0) were significantly higher in male than in female patients. Further investigation found that the correlation between Cer20:0 and IL‐5 was positive in males (ρ = 0.943, P = 0.005) but negative in females (ρ = −0.561, P = 0.030).

Conclusions

Testosterone was negatively correlated with eosinophil inflammatory factors, but estradiol was positively correlated. Male asthma patients had higher ceramide and sphingomyelin levels than female patients. Different sexes had opposite correlations with ceramide and IL‐5, respectively, suggesting that therapeutic strategies targeting ceramide should be different between sexes.
Assessing Measurement Invariance for Applied Research
Authors: Wells Craig S.
Published: May 2021

This book focuses on the practical application of statistical techniques for assessing measurement invariance with less emphasis on theoretical development or exposition. Instead, it describes the methods using a pedagogical framework followed by extensive illustrations that demonstrate how to use software to analyze real data. The chapters illustrate the practical methods to assess measurement invariance and shows how to apply them to a range of data. The computer syntax and data sets used in this book are available for download here: people.umass.edu/cswells.
Uruguay and Contemporary Theories of Wage Coordination: Origins and Stabilization of Segmented Neocorporatism, 2005–2019
Authors: Etchemendy Sebastián
Published: May 2021

This study seeks to explain the rise and performance of “segmented neocorporatism” in Uruguay in light of contemporary theories of wage coordination, largely framed by the Varieties of Capitalism school and its recent critics. First it argues that the legacy of a centralized labor law framework, and a unified union movement, combined with Frente Amplio’s decisive labor empowerment from above to launch neocorporatist wage coordination in the period 2005–10. Second, it analyzes the stabilization of the coordinated model in 2013–19, in times of sluggish growth and labor tensions, evinced in the control of inflation pressures and social conflict. The article concludes that the macroeconomic combination of supply-side and Keynesian policies and the inclusion of precarious workers shaped an egalitarian version of corporatism with important challenges ahead.
Rapid Monitoring of the Abundance and Spread of Exotic Annual Grasses in the Western United States Using Remote Sensing and Machine Learning
Authors: Pastick Neal J. , Wylie Bruce K. , Rigge Matthew B. , Dahal Devendra , Boyte Stephen P. , Jones Matthew O. , Allred Brady W. , Parajuli Sujan , Wu Zhuoting
Published: May 2021

Exotic annual grasses (EAG) are one of the most damaging agents of change in western North America. Despite known socio‐environmental effects of EAG there remains a need to enhance monitoring capabilities for better informing conservation and management practices. Here, we integrate field observations, remote sensing and climate data with machine‐learning techniques to estimate and assess patterns of historical (1985–2019; R2 = 0.86 ± 0.05; MAE = 6.7 ± 1.4%), present (2020), and future (2025–2040) EAG abundance (30‐m) across much of the western United States. Trend analysis revealed that ∼8% and 1% of the landscape experienced significant rises and declines in historical EAG cover, respectively, with hotspots of invasion generally occurring near roads and along low‐to‐mid elevation gradients with warmer and drier conditions. Accurate simulations of the response of EAG to changing environmental conditions, disturbances and management treatments indicate that ecosystem resistance to invasion is largely controlled by long‐term EAG abundance (surrogate for seed bank), time since and frequency of wildfire, and plant community interactions. Ecological thresholds associated with enhanced probabilities of wildfire occurrence and invasion rates indicate that relatively little (10%) EAG cover is needed to heighten these risks. Climate change is expected to push 8% of the landscape across invasion thresholds by 2040, impacting 6% of existing sage‐grouse habitat, and we identify where fuel breaks may be placed to reduce wildfire risks and invasion. Spatially detailed, timely, and accurate depictions of past, present, and future EAG abundance are vital for the protection of life and property and the continued stewardship of sagebrush ecosystems.
Self-reported knowledge about dental caries at young age and variations between dental practitioners in the Ministry of Health in Bahrain
Authors: Alrowaili Eman Flaihan
Published: May 2021

Objectives

To assess basic knowledge on dental caries and its prevention especially in young children and variation thereof between dental practitioners working for the Ministry of Health in Bahrain.

Materials and methods

Self-reported questionnaire was sent to all dentists and dental hygienists.

Results

One hundred and thirty-four dental practitioners responded. The mean knowledge and practice scores for association between diet and dental caries was 64.9 ± 20.1. Females scored higher than males (p = 0.011) and dentists scored higher than dental hygienists (p = 0.009). A low mean score 45.5 ± 19.6 was observed in preventing dental caries in toddlers. Those >40 years of age and those with >15 years of experience have significantly higher scores than other groups (p = 0.009 andp = 0.001), respectively. Mean score for caring for children’s teeth, which covered advice on fluoridated toothpaste, was 63.4 ± 20.9. Younger dentists had higher score than those >40 years of age (p = 0.003). Mean score for frequency of fluoride varnish application was 64.4 ± 15.8 with no significant variation between practitioners.

Conclusion

There is a need to reduce variations and update and improve dental practitioners’ knowledge in regard to risks and prevention of caries at young age.
Diversity and infectivity of the RNA virome among different cryptic species of an agriculturally important insect vector: whitefly Bemisia tabaci
Authors: Huang Hai-Jian , Ye Zhuang-Xin , Wang Xin , Yan Xiao-Tian , Zhang Yan , He Yu-Juan , Qi Yu-Hua , Zhang Xiao-Di , Zhuo Ji-Chong , Lu Gang , Lu Jia-Bao , Mao Qian-Zhuo , Sun Zong-Tao , Yan Fei , Chen Jian-Ping , Zhang Chuan-Xi , Li Jun-Min
Published: May 2021

A large number of insect-specific viruses (ISVs) have recently been discovered, mostly from hematophagous insect vectors because of their medical importance, but little attention has been paid to important plant virus vectors such as the whitefly Bemisia tabaci, which exists as a complex of cryptic species. Public SRA datasets of B. tabaci and newly generated transcriptomes of three Chinese populations are here comprehensively investigated to characterize the whitefly viromes of different cryptic species. Twenty novel ISVs were confidently identified, mostly associated with a particular cryptic species while different cryptic species harbored one or more core ISVs. Microinjection experiments showed that some ISVs might cross-infect between the two invasive whitefly cryptic species, Middle East Asia Minor 1 (MEAM1) and Mediterranean (MED), but others appeared to have a more restricted host range, reflecting the possibility of distinct long-term coevolution of these ISVs and whitefly hosts. Moreover, analysis of the profiles of virus-derived small-interfering RNAs indicated that some of the ISVs can successfully replicate in whitefly and the antiviral RNAi pathway of B. tabaci is actively involved in response to ISV infections. Our study provides a comprehensive analysis of the RNA virome, the distinct relationships and cross-cryptic species infectivity of ISVs in an agriculturally important insect vector.
Evaluating machine learning techniques for archaeological lithic sourcing: a case study of flint in Britain
Authors: Elliot Tom , Morse Robert , Smythe Duane , Norris Ashley
Published: May 2021

It is 50 years since Sieveking et al. published their pioneering research in Nature on the geochemical analysis of artefacts from Neolithic flint mines in southern Britain. In the decades since, geochemical techniques to source stone artefacts have flourished globally, with a renaissance in recent years from new instrumentation, data analysis, and machine learning techniques. Despite the interest over these latter approaches, there has been variation in the quality with which these methods have been applied. Using the case study of flint artefacts and geological samples from England, we present a robust and objective evaluation of three popular techniques, Random Forest, K-Nearest-Neighbour, and Support Vector Machines, and present a pipeline for their appropriate use. When evaluated correctly, the results establish high model classification performance, with Random Forest leading with an average accuracy of 85% (measured through F1 Scores), and with Support Vector Machines following closely. The methodology developed in this paper demonstrates the potential to significantly improve on previous approaches, particularly in removing bias, and providing greater means of evaluation than previously utilised.
The effects of climate change on the Pleistocene rock art of Sulawesi
Authors: Huntley J. , Aubert M. , Oktaviana A. A. , Lebe R. , Hakim B. , Burhan B. , Aksa L. Muhammad , Geria I. Made , Ramli M. , Siagian L. , Brand H. E. A. , Brumm A.
Published: May 2021

The equatorial tropics house some of the earliest rock art yet known, and it is weathering at an alarming rate. Here we present evidence for haloclasty (salt crystallisation) from Pleistocene-aged rock art panels at 11 sites in the Maros-Pangkep limestone karsts of southern Sulawesi. We show how quickly rock art panels have degraded in recent decades, contending that climate-catalysed salt efflorescence is responsible for increasing exfoliation of the limestone cave surfaces that house the ~ 45 to 20-thousand-year-old paintings. These artworks are located in the world’s most atmospherically dynamic region, the Australasian monsoon domain. The rising frequency and severity of El Niño-induced droughts from anthropogenic climate change (that is, higher ambient temperatures and more consecutive dry days), combined with seasonal moisture injected via monsoonal rains retained as standing water in the rice fields and aquaculture ponds of the region, increasingly provide ideal conditions for evaporation and haloclasty, accelerating rock art deterioration.
Longitudinal hippocampal volumetric changes in mice following brain infarction
Authors: Brait Vanessa H. , Wright David K. , Nategh Mohsen , Oman Alexander , Syeda Warda T. , Ermine Charlotte M. , O’Brien Katrina R. , Werden Emilio , Churilov Leonid , Johnston Leigh A. , Thompson Lachlan H. , Nithianantharajah Jess , Jackman Katherine A. , Brodtmann Amy
Published: May 2021

Hippocampal atrophy is increasingly described in many neurodegenerative syndromes in humans, including stroke and vascular cognitive impairment. However, the progression of brain volume changes after stroke in rodent models is poorly characterized. We aimed to monitor hippocampal atrophy occurring in mice up to 48-weeks post-stroke. Male C57BL/6J mice were subjected to an intraluminal filament-induced middle cerebral artery occlusion (MCAO). At baseline, 3-days, and 1-, 4-, 12-, 24-, 36- and 48-weeks post-surgery, we measured sensorimotor behavior and hippocampal volumes from T2-weighted MRI scans. Hippocampal volume—both ipsilateral and contralateral—increased over the life-span of sham-operated mice. In MCAO-subjected mice, different trajectories of ipsilateral hippocampal volume change were observed dependent on whether the hippocampus contained direct infarction, with a decrease in directly infarcted tissue and an increase in non-infarcted tissue. To further investigate these volume changes, neuronal and glial cell densities were assessed in histological brain sections from the subset of MCAO mice lacking hippocampal infarction. Our findings demonstrate previously uncharacterized changes in hippocampal volume and potentially brain parenchymal cell density up to 48-weeks in both sham- and MCAO-operated mice.
Spatio-temporal gait parameters obtained from foot-worn inertial sensors are reliable in healthy adults in single- and dual-task conditions
Authors: Soulard J. , Vaillant J. , Balaguier R. , Vuillerme N.
Published: May 2021

Inertial measurement units (IMUs) are increasingly popular and may be usable in clinical routine to assess gait. However, assessing their intra-session reliability is crucial and has not been tested with foot-worn sensors in healthy participants. The aim of this study was to assess the intra-session reliability of foot-worn IMUs for measuring gait parameters in healthy adults. Twenty healthy participants were enrolled in the study and performed the 10-m walk test in single- and dual-task ('carrying a full cup of water') conditions, three trials per condition. IMUs were used to assess spatiotemporal gait parameters, gait symmetry parameters (symmetry index (SI) and symmetry ratio (SR)), and dual task effects parameters. The relative and the absolute reliability were calculated for each gait parameter. Results showed that spatiotemporal gait parameters measured with foot-worn inertial sensors were reliable; symmetry gait parameters relative reliability was low, and SR showed better absolute reliability than SI; dual task effects were poorly reliable, and taking the mean of the second and the third trials was the most reliable. Foot-worn IMUs are reliable to assess spatiotemporal and symmetry ratio gait parameters but symmetry index and DTE gait parameters reliabilities were low and need to be interpreted with cautious by clinicians and researchers.
Smoking is associated with impaired verbal learning and memory performance in women more than men
Authors: Lewis C. R. , Talboom J. S. , De Both M. D. , Schmidt A. M. , Naymik M. A. , Håberg A. K. , Rundek T. , Levin B. E. , Hoscheidt S. , Bolla Y. , Brinton R. D. , Hay M. , Barnes C. A. , Glisky E. , Ryan L. , Huentelman M. J.
Published: May 2021

Vascular contributions to cognitive impairment and dementia (VCID) include structural and functional blood vessel injuries linked to poor neurocognitive outcomes. Smoking might indirectly increase the likelihood of cognitive impairment by exacerbating vascular disease risks. Sex disparities in VCID have been reported, however, few studies have assessed the sex-specific relationships between smoking and memory performance and with contradictory results. We investigated the associations between sex, smoking, and cardiovascular disease with verbal learning and memory function. Using MindCrowd, an observational web-based cohort of ~ 70,000 people aged 18–85, we investigated whether sex modifies the relationship between smoking and cardiovascular disease with verbal memory performance. We found significant interactions in that smoking is associated with verbal learning performance more in women and cardiovascular disease more in men across a wide age range. These results suggest that smoking and cardiovascular disease may impact verbal learning and memory throughout adulthood differently for men and women.
Developments in data science solutions for carnivore tooth pit classification
Authors: Courtenay Lloyd A. , Herranz-Rodrigo Darío , González-Aguilera Diego , Yravedra José
Published: May 2021

Competition for resources is a key question in the study of our early human evolution. From the first hominin groups, carnivores have played a fundamental role in the ecosystem. From this perspective, understanding the trophic pressure between hominins and carnivores can provide valuable insights into the context in which humans survived, interacted with their surroundings, and consequently evolved. While numerous techniques already exist for the detection of carnivore activity in archaeological and palaeontological sites, many of these techniques present important limitations. The present study builds on a number of advanced data science techniques to confront these issues, defining methods for the identification of the precise agents involved in carcass consumption and manipulation. For the purpose of this study, a large sample of 620 carnivore tooth pits is presented, including samples from bears, hyenas, jaguars, leopards, lions, wolves, foxes and African wild dogs. Using 3D modelling, geometric morphometrics, robust data modelling, and artificial intelligence algorithms, the present study obtains between 88 and 98% accuracy, with balanced overall evaluation metrics across all datasets. From this perspective, and when combined with other sources of taphonomic evidence, these results show that advanced data science techniques can be considered a valuable addition to the taphonomist’s toolkit for the identification of precise carnivore agents via tooth pit morphology.
Long-term results of sirolimus treatment in lymphangioleiomyomatosis: a single referral centre experience
Authors: Revilla-López Eva , Berastegui Cristina , Méndez Alejandra , Sáez-Giménez Berta , Ruiz de Miguel Victoria , López-Meseguer Manuel , Monforte Victor , Bravo Carlos , Pujana Miguel Angel , Ramon Maria Antonia , Gómez-Ollés Susana , Roman Antonio ,   The Vall d’Hebron Multidisciplinary Cystic Lung Disease Group, Bello Irene , Burgos Rosa , Escobar Roser , Ferrándiz-Pulido Carla , Gómez Alba , Pallisa Esther , Palomares Gloria , Salicrú Sabina , Sánchez Martínez Ana Lucía , Sansano Irene , Sellarés Joana
Published: May 2021

There are few published data on long-term treatment with sirolimus in lymphangioleiomyomatosis (LAM). The objective of this study was to describe the long-term effect of sirolimus in a series of LAM patients followed up in a referral centre, focusing on pulmonary function. We retrospectively reviewed a series of 48 patients with LAM diagnosed, followed up and treated with sirolimus in a single centre. Response to sirolimus was evaluated at 1 and 5 years. A negative sirolimus response was defined as an FEV1 decline greater than − 75 ml/year. A mixed-effects model was used to estimate the longitudinal changes in FEV1 (average slope), both as absolute (ml/year) and as predicted values (%predicted/year). From a total of 48 patients, 9 patients underwent lung transplantation and 4 died during the study. Mean (95% CI) FEV1 slope over 5 years was − 0.14 (− 26.13 to 25.85) ml/year in the whole LAM group, 42.55 (14.87 to 70.22) ml/year in the responder group, − 54.00 (− 71.60 to − 36.39) ml/year in the partial responder group and − 84.19 (− 113.5 to − 54.0) ml/year in the non-responder group. After 5 years of sirolimus treatment 59% had a positive response, 30% had a partial response and 11% had a negative response. Our study found that sirolimus treatment had a positive long-term effect on most LAM patients.
Joint angle estimation with wavelet neural networks
Authors: Sivakumar Saaveethya , Gopalai Alpha Agape , Lim King Hann , Gouwanda Darwin , Chauhan Sunita
Published: May 2021

This paper presents a wavelet neural network (WNN) based method to reduce reliance on wearable kinematic sensors in gait analysis. Wearable kinematic sensors hinder real-time outdoor gait monitoring applications due to drawbacks caused by multiple sensor placements and sensor offset errors. The proposed WNN method uses vertical Ground Reaction Forces (vGRFs) measured from foot kinetic sensors as inputs to estimate ankle, knee, and hip joint angles. Salient vGRF inputs are extracted from primary gait event intervals. These selected gait inputs facilitate future integration with smart insoles for real-time outdoor gait studies. The proposed concept potentially reduces the number of body-mounted kinematics sensors used in gait analysis applications, hence leading to a simplified sensor placement and control circuitry without deteriorating the overall performance.
In silico analysis suggests the RNAi-enhancing antibiotic enoxacin as a potential inhibitor of SARS-CoV-2 infection
Authors: Ahmadi Amirhossein , Moradi Sharif
Published: May 2021

COVID-19 has currently become the biggest challenge in the world. There is still no specific medicine for COVID-19, which leaves a critical gap for the identification of new drug candidates for the disease. Recent studies have reported that the small-molecule enoxacin exerts an antiviral activity by enhancing the RNAi pathway. The aim of this study is to analyze if enoxacin can exert anti-SARS-CoV-2 effects. We exploit multiple computational tools and databases to examine (i) whether the RNAi mechanism, as the target pathway of enoxacin, could act on the SARS-CoV-2 genome, and (ii) microRNAs induced by enoxacin might directly silence viral components as well as the host cell proteins mediating the viral entry and replication. We find that the RNA genome of SARS-CoV-2 might be a suitable substrate for DICER activity. We also highlight several enoxacin-enhanced microRNAs which could target SARS-CoV-2 components, pro-inflammatory cytokines, host cell components facilitating viral replication, and transcription factors enriched in lung stem cells, thereby promoting their differentiation and lung regeneration. Finally, our analyses identify several enoxacin-targeted regulatory modules that were critically associated with exacerbation of the SARS-CoV-2 infection. Overall, our analysis suggests that enoxacin could be a promising candidate for COVID-19 treatment through enhancing the RNAi pathway.
Easy ultrastructural insight into the internal morphology of biological specimens by Atomic Force Microscopy
Authors: Herrmann Fabian Christopher
Published: May 2021

As a topographical technique, Atomic Force Microscopy (AFM) needs to establish direct interactions between a given sample and the measurement probe in order to create imaging information. The elucidation of internal features of organisms, tissues and cells by AFM has therefore been a challenging process in the past. To overcome this hindrance, simple and fast embedding, sectioning and dehydration techniques are presented, allowing the easy access to the internal morphology of virtually any organism, tissue or cell by AFM. The study at hand shows the applicability of the proposed protocol to exemplary biological samples, the resolution currently allowed by the approach as well as advantages and shortcomings compared to classical ultrastructural microscopic techniques like electron microscopy. The presented cheap, facile, fast and non-toxic experimental protocol might introduce AFM as a universal tool for the elucidation of internal ultrastructural detail of virtually any given organism, tissue or cell.
Enhancement of cerebrovascular 4D flow MRI velocity fields using machine learning and computational fluid dynamics simulation data
Authors: Rutkowski David R. , Roldán-Alzate Alejandro , Johnson Kevin M.
Published: May 2021

Blood flow metrics obtained with four-dimensional (4D) flow phase contrast (PC) magnetic resonance imaging (MRI) can be of great value in clinical and experimental cerebrovascular analysis. However, limitations in both quantitative and qualitative analyses can result from errors inherent to PC MRI. One method that excels in creating low-error, physics-based, velocity fields is computational fluid dynamics (CFD). Augmentation of cerebral 4D flow MRI data with CFD-informed neural networks may provide a method to produce highly accurate physiological flow fields. In this preliminary study, the potential utility of such a method was demonstrated by using high resolution patient-specific CFD data to train a convolutional neural network, and then using the trained network to enhance MRI-derived velocity fields in cerebral blood vessel data sets. Through testing on simulated images, phantom data, and cerebrovascular 4D flow data from 20 patients, the trained network successfully de-noised flow images, decreased velocity error, and enhanced near-vessel-wall velocity quantification and visualization. Such image enhancement can improve experimental and clinical qualitative and quantitative cerebrovascular PC MRI analysis.
TBC1D24 emerges as an important contributor to progressive postlingual dominant hearing loss
Authors: Oziębło Dominika , Leja Marcin L. , Lazniewski Michal , Sarosiak Anna , Tacikowska Grażyna , Kochanek Krzysztof , Plewczynski Dariusz , Skarżyński Henryk , Ołdak Monika
Published: May 2021

Several TBC1D24 variants are causally involved in the development of profound, prelingual hearing loss (HL) and different epilepsy syndromes inherited in an autosomal recessive manner. Only two TBC1D24 pathogenic variants have been linked with postlingual progressive autosomal dominant HL (ADHL). To determine the role of TBC1D24 in the development of ADHL and to characterize the TBC1D24-related ADHL, clinical exome sequencing or targeted multigene (n = 237) panel were performed for probands (n = 102) from multigenerational ADHL families. In four families, TBC1D24-related HL was found based on the identification of three novel, likely pathogenic (c.553G>A, p.Asp185Asn; c.1460A>T, p. His487Leu or c.1461C>G, p.His487Gln) and one known (c.533C>T, p.Ser178Leu) TBC1D24 variant. Functional consequences of these variants were characterized by analyzing the proposed homology models of the human TBC1D24 protein. Variants not only in the TBC (p.Ser178Leu, p.Asp185Asn) but also in the TLDc domain (p.His487Gln, p.His487Leu) are involved in ADHL development, the latter two mutations probably affecting interactions between the domains. Clinically, progressive HL involving mainly mid and high frequencies was observed in the patients (n = 29). The progression of HL was calculated by constructing age-related typical audiograms. TBC1D24-related ADHL originates from the cochlear component of the auditory system, becomes apparent usually in the second decade of life and accounts for approximately 4% of ADHL cases. Given the high genetic heterogeneity of ADHL, TBC1D24 emerges as an important contributor to this type of HL.
Repurposing ketoconazole as an exosome directed adjunct to sunitinib in treating renal cell carcinoma
Authors: Greenberg Jacob W. , Kim Hogyoung , Moustafa Ahmed A. , Datta Amrita , Barata Pedro C. , Boulares A. Hamid , Abdel-Mageed Asim B. , Krane Louis S.
Published: May 2021

Renal Cell Carcinoma (RCC) is the most common form of kidney cancer, with clear cell RCC (ccRCC) representing about 85% of all RCC tumors. There are limited curable treatments available for metastatic ccRCC because this disease is unresponsive to conventional targeted systemic pharmacotherapy. Exosomes (Exo) are small extracellular vesicles (EVs) secreted from cancer cells with marked roles in tumoral signaling and pharmacological resistance. Ketoconazole (KTZ) is an FDA approved anti-fungal medication which has been shown to suppress exosome biogenesis and secretion, yet its role in ccRCC has not been identified. A time-course, dose-dependent analysis revealed that KTZ selectively decreased secreted Exo in tumoral cell lines. Augmented Exo secretion was further evident by decreased expression of Exo biogenesis (Alix and nSMase) and secretion (Rab27a) markers. Interestingly, KTZ-mediated inhibition of Exo biogenesis was coupled with inhibition of ERK1/2 activation. Next, selective inhibitors were employed and showed ERK signaling had a direct role in mediating KTZ’s inhibition of exosomes. In sunitinib resistant 786-O cells lines, the addition of KTZ potentiates the efficacy of sunitinib by causing Exo inhibition, decreased tumor proliferation, and diminished clonogenic ability of RCC cells. Our findings suggest that KTZ should be explored as an adjunct to current RCC therapies.
Moral labels increase cooperation and costly punishment in a Prisoner’s Dilemma game with punishment option
Authors: Mieth Laura , Buchner Axel , Bell Raoul
Published: May 2021

To determine the role of moral norms in cooperation and punishment, we examined the effects of a moral-framing manipulation in a Prisoner’s Dilemma game with a costly punishment option. In each round of the game, participants decided whether to cooperate or to defect. The Prisoner’s Dilemma game was identical for all participants with the exception that the behavioral options were paired with moral labels (“I cooperate” and “I cheat”) in the moral-framing condition and with neutral labels (“A” and “B”) in the neutral-framing condition. After each round of the Prisoner’s Dilemma game, participants had the opportunity to invest some of their money to punish their partners. In two experiments, moral framing increased moral and hypocritical punishment: participants were more likely to punish partners for defection when moral labels were used than when neutral labels were used. When the participants’ cooperation was enforced by their partners’ moral punishment, moral framing did not only increase moral and hypocritical punishment but also cooperation. The results suggest that moral framing activates a cooperative norm that specifically increases moral and hypocritical punishment. Furthermore, the experience of moral punishment by the partners may increase the importance of social norms for cooperation, which may explain why moral framing effects on cooperation were found only when participants were subject to moral punishment.
Crossover point of the field effect transistor and interconnect applications in turbostratic multilayer graphene nanoribbon channel
Authors: Negishi Ryota , Yamamoto Katsuma , Tanaka Hirofumi , Mojtahedzadeh Seyed Ali , Mori Nobuya , Kobayashi Yoshihiro
Published: May 2021

The electrical transport properties of a turbostratic multilayer graphene nanoribbon (GNR) with various number of layers (1–8 layers) were investigated using a field effect transistor with a single GNR channel. In the turbostratic multilayer GNR with 5 layers or less, the carrier mobility and Ion/Ioff ratio in the FETs were improved by slightly increasing the conductance with increasing the number of layers, meaning that the excellent semiconducting characteristic. The improvement of the carrier transport properties promotes by the turbostratic stacking structure. In the turbostratic multilayer GNR with 6 layers or more, although the Ion/Ioff ratio degraded, the conductance extremely improved with increasing the number of layers. This indicates that the turbostratic multilayer GNR with thicker number of layers becomes the significantly lower resistivity wire as a metallic characteristic. We revealed that the crossover point of the physical properties between the semiconducting and metallic characteristics is determined by the strength to screen the surrounding environment effects such as charged impurity on the substrate. Our comprehensive investigation provides a design guidance for the various electrical device applications of GNR materials.
Repurposing potential of posaconazole and grazoprevir as inhibitors of SARS-CoV-2 helicase
Authors: Abidi Syed Hani , Almansour Nahlah Makki , Amerzhanov Daulet , Allemailem Khaled S. , Rafaqat Wardah , Ibrahim Mahmoud A. A. , la Fleur Philip , Lukac Martin , Ali Syed
Published: May 2021

As the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic engulfs millions worldwide, the quest for vaccines or drugs against the virus continues. The helicase protein of SARS-CoV-2 represents an attractive target for drug discovery since inhibition of helicase activity can suppress viral replication. Using in silico approaches, we have identified drugs that interact with SARS-CoV-2 helicase based on the presence of amino acid arrangements matching binding sites of drugs in previously annotated protein structures. The drugs exhibiting an RMSD of ≤ 3.0 Å were further analyzed using molecular docking, molecular dynamics (MD) simulation, and post-MD analyses. Using these approaches, we found 12 drugs that showed strong interactions with SARS-CoV-2 helicase amino acids. The analyses were performed using the recently available SARS-CoV-2 helicase structure (PDB ID: 5RL6). Based on the MM-GBSA approach, out of the 12 drugs, two drugs, namely posaconazole and grazoprevir, showed the most favorable binding energy, − 54.8 and − 49.1 kcal/mol, respectively. Furthermore, of the amino acids found conserved among all human coronaviruses, 10/11 and 10/12 were targeted by, respectively, grazoprevir and posaconazole. These residues are part of the crucial DEAD-like helicase C and DEXXQc_Upf1-like/ DEAD-like helicase domains. Strong interactions of posaconazole and grazoprevir with conserved amino acids indicate that the drugs can be potent against SARS-CoV-2. Since the amino acids are conserved among the human coronaviruses, the virus is unlikely to develop resistance mutations against these drugs. Since these drugs are already in use, they may be immediately repurposed for SARS-CoV-2 therapy.
Behavioural and oceanographic isolation of an island-based jellyfish (Copula sivickisi, Class Cubozoa) population
Authors: Schlaefer Jodie A. , Wolanski Eric , Lambrechts Jonathan , Kingsford Michael J.
Published: May 2021

Cubozoan jellyfish are classified as plankton despite the strong swimming and orientation abilities of cubomedusae. How these capabilities could affect cubozoan population structures is poorly understood. Medusae of the cubozoan Copula sivickisi can uniquely attach to surfaces with the sticky pads on their bells. Biophysical modelling was used to investigate the spatial scales of connectivity in a C. sivickisi population. When the medusae were active at night they could maintain their observed distribution on fringing reef if they attached to the reef when the current speed exceeded a moderate threshold. This behaviour facilitated the isolation of a C. sivickisi population on reefs fringing Magnetic Island, Queensland, Australia. Within this distribution, there was considerable within bay retention and medusae rarely travelled > 3 km. The few (< 0.1%) medusae lost from the island habitat were largely advected into open water and away from the mainland coast which lies 8 km from the island. Given that successful emigration is unlikely, the island population probably represents a stock that is ecologically distinct from any mainland populations. The cosmopolitan distribution of C. sivickisi could contain incipient or cryptic species given the small scales of connectivity demonstrated here.
Using artificial intelligence and longitudinal location data to differentiate persons who develop posttraumatic stress disorder following childhood trauma
Authors: Lekkas Damien , Jacobson Nicholas C.
Published: May 2021

Post-traumatic stress disorder (PTSD) is characterized by complex, heterogeneous symptomology, thus detection outside traditional clinical contexts is difficult. Fortunately, advances in mobile technology, passive sensing, and analytics offer promising avenues for research and development. The present study examined the ability to utilize Global Positioning System (GPS) data, derived passively from a smartphone across seven days, to detect PTSD diagnostic status among a cohort (N = 185) of high-risk, previously traumatized women. Using daily time spent away and maximum distance traveled from home as a basis for model feature engineering, the results suggested that diagnostic group status can be predicted out-of-fold with high performance (AUC = 0.816, balanced sensitivity = 0.743, balanced specificity = 0.8, balanced accuracy = 0.771). Results further implicate the potential utility of GPS information as a digital biomarker of the PTSD behavioral repertoire. Future PTSD research will benefit from application of GPS data within larger, more diverse populations.
Genomic selection signatures in autism spectrum disorder identifies cognitive genomic tradeoff and its relevance in paradoxical phenotypes of deficits versus potentialities
Authors: Prakash Anil , Banerjee Moinak
Published: May 2021

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by paradoxical phenotypes of deficits as well as gain in brain function. To address this a genomic tradeoff hypothesis was tested and followed up with the biological interaction and evolutionary significance of positively selected ASD risk genes. SFARI database was used to retrieve the ASD risk genes while for population datasets 1000 genome data was used. Common risk SNPs were subjected to machine learning as well as independent tests for selection, followed by Bayesian analysis to identify the cumulative effect of selection on risk SNPs. Functional implication of these positively selected risk SNPs was assessed and subjected to ontology analysis, pertaining to their interaction and enrichment of biological and cellular functions. This was followed by comparative analysis with the ancient genomes to identify their evolutionary patterns. Our results identified significant positive selection signals in 18 ASD risk SNPs. Functional and ontology analysis indicate the role of biological and cellular processes associated with various brain functions. The core of the biological interaction network constitutes genes for cognition and learning while genes in the periphery of the network had direct or indirect impact on brain function. Ancient genome analysis identified de novo and conserved evolutionary selection clusters. The de-novo evolutionary cluster represented genes involved in cognitive function. Relative enrichment of the ASD risk SNPs from the respective evolutionary cluster or biological interaction networks may help in addressing the phenotypic diversity in ASD. This cognitive genomic tradeoff signatures impacting the biological networks can explain the paradoxical phenotypes in ASD.
Development and comparison of novel bioluminescent mouse models of pancreatic neuroendocrine neoplasm metastasis
Authors: Kaemmer Courtney A. , Umesalma Shaikamjad , Maharjan Chandra K. , Moose Devon L. , Narla Goutham , Mott Sarah L. , Zamba Gideon K. D. , Breheny Patrick , Darbro Benjamin W. , Bellizzi Andrew M. , Henry Michael D. , Quelle Dawn E.
Published: May 2021

Pancreatic neuroendocrine neoplasms (pNENs) are slow growing cancers of increasing incidence that lack effective treatments once they become metastatic. Unfortunately, nearly half of pNEN patients present with metastatic liver tumors at diagnosis and current therapies fail to improve overall survival. Pre-clinical models of pNEN metastasis are needed to advance our understanding of the mechanisms driving the metastatic process and for the development of novel, targeted therapeutic interventions. To model metastatic dissemination of tumor cells, human pNEN cell lines (BON1 and Qgp1) stably expressing firefly luciferase (luc) were generated and introduced into NSG immunodeficient mice by intracardiac (IC) or intravenous (IV) injection. The efficiency, kinetics and distribution of tumor growth was evaluated weekly by non-invasive bioluminescent imaging (BLI). Tumors formed in all animals in both the IC and IV models. Bioluminescent Qgp1.luc cells preferentially metastasized to the liver regardless of delivery route, mimicking the predominant site of pNEN metastasis in patients. By comparison, BON1.luc cells most commonly formed lung tumors following either IV or IC administration and colonized a wider variety of tissues than Qgp1.luc cells. These models provide a unique platform for testing candidate metastasis genes and anti-metastatic therapies for pNENs.
Mechanistic insights into dehydrocoupling of amine boranes using dinuclear zirconocene complexes
Authors: Lindenau Kevin , Jannsen Nora , Rippke Mirko , Al Hamwi Hanan , Selle Carmen , Drexler Hans-Joachim , Spannenberg Anke , Sawall Mathias , Neymeyr Klaus , Heller Detlef , Reiß Fabian , Beweries Torsten
Published: May 2021

Catalytic dehydrocoupling of H3B·NMe2H using Cp2Zr(Cl)(μ-Me3SiC3SiMe3)Zr(Cl)Cp2(1)/MeLi was studied. Spectroscopic monitoring and stoichiometric experiments show the formation and interconversion of several catalytically active Zr species.
High degradation efficiency of sulfamethazine with the dual-reaction-center Fe–Mn–SiO2 Fenton-like nanocatalyst in a wide pH range
Authors: Panjwani Manoj Kumar , Wang Qing , Ma Yueming , Lin Yuxuan , Xiao Feng , Yang Shaoxia
Published: May 2021

The development of a heterogeneous Fenton-like catalyst, possessing a high degradation efficiency in a wide pH range, is crucial for wastewater treatment.
Recent advances in urea- and thiourea-containing compounds: focus on innovative approaches in medicinal chemistry and organic synthesis
Authors: Ronchetti Riccardo , Moroni Giada , Carotti Andrea , Gioiello Antimo , Camaioni Emidio
Published: May 2021

Urea and thiourea represent privileged structures in medicinal chemistry.
A noncovalent hybrid of [Pd(phen)(OAc)2] and st-DNA for the enantioselective hydroamination of β-nitrostyrene with methoxyamine
Authors: Pal Mrityunjoy , Musib Dulal , Pal Maynak , Rana Gopal , Bag Gobinda , Dutta Subrata , Roy Mithun
Published: May 2021

A DNA-based palladium catalyst was used as a strategic tool for the sustainable and enantioselective Markonicov hydroamination of β-nitrostyrene with methoxyamine in aqueous medium at room temperature.
Ultra-stretchable and healable hydrogel-based triboelectric nanogenerators for energy harvesting and self-powered sensing
Authors: Li Guoxia , Li Longwei , Zhang Panpan , Chang Caiyun , Xu Fan , Pu Xiong
Published: May 2021

An ultra-stretchable and self-healing hydrogel is developed with graphene oxide and Laponite as collaborative physical crosslinking points, which is utilized in triboelectric nanogenerators for mechanical energy harvesting and self-powered sensing.
A ratiometric fluorescent sensor for rapid detection of the pyroglutamate aminopeptidase-1 in mouse tumors
Authors: Cao Ting , Zhang Liang , Zheng Lei , Qian Jing , Iqbal Anam , Iqbal Kanwal , Qin Wenwu , Liu Yun
Published: May 2021

A long-emission ratiometric fluorescence sensor (DP-1) for the specific detection of PGP-1in vivoandin vitrowas first designed and synthesized.
From radical to triradical thin film processes: the Blatter radical derivatives
Authors: Calzolari Arrigo , Rajca Andrzej , Casu Maria Benedetta
Published: May 2021

Thermal evaporation of (poly)radicals is possible. More than one radical site in a molecule makes it more reactive, narrowing the windows left for thin film evaporation, and favouring island formation rather than two-dimensional growth.
Intraspecific variation in diel patterns of rocky reef use suggests temporal partitioning in Port Jackson sharks
Authors: Bass Nathan Charles , Day Joanna , Guttridge Tristan L. , Knott Nathan A. , Brown Culum
Published: May 2021

Limited information exists about the temporal residency patterns of marine predators, especially at the individual level. Temporal partitioning of resources can reduce intra-specific competition, but this has seldom been examined in predators in marine ecosystems. Here, we used 8 years of acoustic telemetry data from 27 receivers deployed in a large coastal embayment to examine the temporal residency of 51 Port Jackson sharks (Heterodontus portusjacksoni), during their breeding season. We found that the residency lengths of male and female Port Jackson sharks on breeding reefs differed throughout the breeding season, with males showing longer residency at the start of the season and females showing longer residency at the end of the season. Port Jackson sharks also showed a 24-h or diel periodicity in their detection patterns. Although the majority of individuals were nocturnal, a small proportion of sharks was detected more frequently during the day, possibly to reduce competition for resources. Surprisingly, there was no difference in the sex ratio nor the size of diurnal and nocturnal individuals. This study provides long-term insight into the temporal residency patterns of mesopredatory sharks at a breeding site and, more broadly, our results highlight the importance of studying temporal variation at the individual level in movement ecology studies.