bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Mouse Models of Autism Spectrum Disorder Present Subtle Heterogenous Cardiac Abnormalities
Authors: Assimopoulos Stephania , Hammill Christopher , Fernandes Darren J. , Spencer Noakes Tara Leigh , Zhou Yu-Qing , Nutter Lauryl M. J. , Ellegood Jacob , Anagnostou Evdokia , Sled John G. , Lerch Jason P. 
Published: October 2021

AbstractBackgroundAutism Spectrum Disorder (ASD) and Congenital Heart Disease (CHD) are strongly linked on a functional and genetic level. Most work has been focused on neurodevelopmental abnormalities in CHD. Conversely, cardiac abnormalities in ASD have been less studied. In this work we investigate the prevalence of cardiac comorbidities relative to genetic contributors of ASD.MethodsUsing high frequency ultrasound imaging, we screened 9 mouse models with ASD-related genetic alterations (Arid1b(+/-),Chd8(+/-), 16p11.2 (deletion),Sgsh(+/-),Sgsh(-/-),Shank3 Δexon 4-9(+/-),Shank3 Δexon 4-9(-/-),Fmr1(-/-),Vps13b(+/-)), and pooled wild-type littermates (WT). Using a standardised imaging protocol, we measured heart rate (HR), aorta diameter (AoD), thickness and thickening of the left-ventricular (LV) anterior and posterior walls, LV chamber diameter, fractional shortening, stroke volume and cardiac output, Peak E and A velocity ratio of mitral inflow, Velocity Time Integral (VTI) through the ascending aorta.ResultsMutant groups presented small-scale alterations in cardiac structure and function compared to WTs. A greater number of significant differences was observed among mutant groups than between mutant groups and WTs. Mutant groups differed primarily in measures of structure (LV chamber diameter and anterior wall thickness, HR, AoD). When compared to WTs, they differed in both structure and function (LV anterior wall thickness and thickening, chamber diameter and fractional shortening, HR). The mutant groups with most differences to WTs were 16p11.2 (deletion),Fmrl(-/-),Arid1b(+/-). Among mutant groups, the groups differing most from others were 16p11.2 (deletion),Sgsh(+/-),Fmrl(-/-). Our results broadly recapitulate the associated clinical findings.LimitationsVarious genetically driven cardiac abnormalities occur early in life, so repeating this work in non-adult mice may be valuable. To identify possible sex differences, we must extend this work to female mice. The downsampling procedure used (total correlation calculation) must be verified. Only indirect comparison between our results and clinical literature is possible due to differing study designs.ConclusionsThe characteristic heterogeneity of ASD was recapitulated in the observed cardiac phenotype. The type of measures (morphological, functional) mutant groups differ in can highlight common underlying mechanisms. Clinically, knowledge of cardiac abnormalities in ASD can be essential as even non-lethal cardiac abnormalities can impact normal development.
Controlling Selectivity of Modular Microbial Biosynthesis of Butyryl-CoA-Derived Designer Esters
Authors: Lee Jong-Won , Trinh Cong T. 
Published: October 2021

AbstractShort-chain esters have broad utility as flavors, fragrances, solvents, and biofuels. Controlling selectivity of ester microbial biosynthesis has been an outstanding metabolic engineering problem. Here, we present a generalizable framework to enable thede novofermentative microbial biosynthesis of butyryl-CoA-derived designer esters (e.g., butyl acetate, ethyl butyrate, butyl butyrate) with controllable selectivity. Using the modular design principles, we generated the butyryl-CoA-derived ester pathways as exchangeable production modules compatible with an engineered chassis cell for anaerobic production of designer esters. We designed these modules derived from an acyl-CoA submodule (e.g., acetyl-CoA, butyryl-CoA), an alcohol submodule (e.g., ethanol, butanol), a cofactor regeneration submodule (e.g., NADH), and an alcohol acetyltransferase (AAT) submodule (e.g., ATF1, SAAT) for rapid module construction and optimization by manipulating replication (e.g., plasmid copy number), transcription (e.g., promoters), translation (e.g., codon optimization), pathway enzymes, and pathway induction conditions. To further enhance production of designer esters with high selectivity, we systematically screened various strategies of protein solubilization using protein fusion tags and chaperones to improve the soluble expression of multiple pathway enzymes. Finally, our engineered ester-producing strains could achieve 19-fold increase in butyl acetate production (0.64 g/L, 96% selectivity), 6-fold increase in ethyl butyrate production (0.41 g/L, 86% selectivity), and 13-fold increase in butyl butyrate production (0.45 g/L, 54% selectivity) as compared to the initial strains. Overall, this study presented a generalizable framework to engineer modular microbial platforms for anaerobic production of butyryl-CoA-derived designer esters from renewable feedstocks.
Resolving the 3D rotational and translational dynamics of single molecules using radially and azimuthally polarized fluorescence
Authors: Zhang Oumeng , Zhou Weiyan , Lu Jin , Wu Tingting , Lew Matthew D. 
Published: October 2021

AbstractWe report a radially and azimuthally polarized (raPol) microscope for high detection and estimation performance in single-molecule orientation-localization microscopy (SMOLM). With 5000 photons detected from Nile red (NR) transiently bound within supported lipid bilayers (SLBs), raPol SMOLM achieves 2.9 nm localization precision, 1.5° orientation precision, and 0.17 sr precision in estimating rotational wobble. Within DPPC SLBs, SMOLM imaging reveals the existence of randomly oriented binding pockets that prevent NR from freely exploring all orientations. Treating the SLBs with cholesterol-loaded methyl-β-cyclodextrin (MβCD-chol) causes NR’s orientational diffusion to be dramatically reduced, but curiously, NR’s median lateral displacements drastically increase from 20.8 nm to 75.5 nm (200 ms time lag). These jump diffusion events overwhelmingly originate from cholesterol-rich nanodomains within the SLB. These detailed measurements of single-molecule rotational and translational dynamics are made possible by raPol’s high measurement precision and are not detectable in standard SMLM.
The miR-124-AMPAR pathway connects polygenic risks with behavioral changes shared between schizophrenia and bipolar disorder
Authors: Namkung Ho , Yukitake Hiroshi , Fukudome Daisuke , Lee Brian J. , Ursini Gianluca , Lam Shravika , Kannan Suvarnambiga , Saito Atsushi , Niwa Minae , Sharma Kamal , Zandi Peter , Jaaro-Peled Hanna , Ishizuka Koko , Chatterjee Nilanjan , Huganir Richard , Sawa Akira 
Published: October 2021

SUMMARYSchizophrenia (SZ) and bipolar disorder (BP) are highly heritable major psychiatric disorders that share a substantial portion of genetic risk as well as their clinical manifestations. This raises a fundamental question of whether, and how, common neurobiological pathways translate their shared polygenic risks into shared clinical manifestations. The present study shows the miR-124-AMPAR pathway as a key common neurobiological mediator that connects polygenic risks with behavioral changes shared between these two psychotic disorders. We discovered upregulation of miR-124 in biopsied neuronal cells and postmortem prefrontal cortex from both SZ and BP patients, implying its role not only as a biomarker, but also as a pathophysiological mediator. Intriguingly, the upregulation is associated with the polygenic risks shared between these two disorders. Seeking mechanistic dissection, we generated a mouse model that upregulates miR-124 in the medial prefrontal cortex, which includes brain regions homologous to sub-regions of the human prefrontal cortex. We demonstrated that upregulation of miR-124 increases GRIA2-lacking calcium permeable-AMPARs and perturbs AMPAR-mediated excitatory synaptic transmission, leading to deficits in the behavioral dimensions shared between SZ and BP.
Proteomic and functional comparison between human induced and embryonic stem cells
Authors: Brenes Alejandro J. , Griesser Eva , Sinclair Linda V. , Davidson Lindsay , Prescott Alan R. , Singh Francois , Hogg Elizabeth K.J. , Espejo-Serrano Carmen , Jiang Hao , Yoshikawa Harunori , Platani Melpomeni , Swedlow Jason , Findlay Greg M. , Cantrell Doreen A. , Lamond Angus I. 
Published: October 2021

AbstractHuman induced pluripotent stem cells (hiPSCs) have great potential to be used as alternatives to embryonic stem cells (hESCs) in regenerative medicine and disease modelling, thereby avoiding many of the ethical issues arising from the use of embryo-derived cells. However, despite clear similarities between the two cell types, it is likely they are not identical. In this study, we characterise the proteomes of multiple hiPSC and hESC lines derived from independent donors. We find that while hESCs and hiPSCs express a near identical set of proteins, they show consistent quantitative differences in the expression levels of a wide subset of proteins.hiPSCs have increased total protein content, while maintaining a comparable cell cycle profile to hESCs. The proteomic data show hiPSCs have significantly increased abundance of vital cytoplasmic and mitochondrial proteins required to sustain high growth rates, including nutrient transporters and metabolic proteins, which correlated with phenotypic differences between hiPSCs and hESCs. Thus, higher levels of glutamine transporters correlated with increased glutamine uptake, while higher levels of proteins involved in lipid synthesis correlated with increased lipid droplet formation. Some of the biggest metabolic changes were seen in proteins involved in mitochondrial metabolism, with corresponding enhanced mitochondrial potential, shown experimentally using high-resolution respirometry. hiPSCs also produced higher levels of secreted proteins, including ECM components and growth factors, some with known tumorigenic properties, as well as proteins involved in the inhibition of the immune system. Our data indicate that reprogramming of human fibroblasts to iPSCs effectively restores protein expression in cell nuclei to a state comparable to hESCs, but does not similarly restore the profile of cytoplasmic and mitochondrial proteins, with consequences for cell phenotypes affecting growth and metabolism. The data improve understanding of the molecular differences between induced and embryonic stem cells, with implications for potential risks and benefits for their use in future disease modelling and therapeutic applications.
Identifying the oncogenic potential of gene fusions exploiting miRNAs
Authors: Barrese Venere S , Montemurro Marilisa , Lovino Marta , Ficarra Elisa 
Published: October 2021

AbstractBackgroundIt is estimated that oncogenic gene fusions cause about 20% of human cancer morbidity. Identifying potentially oncogenic gene fusions may improve affected patients’ diagnosis and treatment. Previous approaches to this issue included exploiting specific gene-related information, such as gene function and regulation. Here we propose a model that profits from the previous findings and includes the microRNAs in the oncogenic assessment. We present a classifier called ChimerDriver for the classification of gene fusions as oncogenic or not oncogenic. ChimerDriver is based on a specifically designed neural network and trained on genetic and post-transcriptional information to obtain a reliable classification.Results and discussionThe designed neural network integrates information related to transcription factors, gene ontologies, microRNAs and other detailed information related to the functions of the genes involved in the fusion and the gene fusion structure. As a result, the performances on the test set reached 0.83 f1-score and 96% recall. The comparison with state-of-the-art tools returned comparable or higher results. Moreover, ChimerDriver performed well in a real-world case where 21 out of 24 validated gene fusion samples were detected by the gene fusion detection tool Starfusion.ConclusionsChimerDriver integrated transcriptional and post-transcriptional information in an ad-hoc designed neural network to effectively discriminate oncogenic gene fusions from passenger ones.
Identifying the latent shortcomings of force account projects in Tanzania: the case of construction projects in the education sector
Authors: Matto Mordecai Chrysostom 
Published: October 2021

PurposeThe study investigates the latent shortcomings of projects implemented under the force account approach. The study offers implications to the policymakers, practitioners and society at large for the effective and efficient application of the force account method in construction projects.Design/methodology/approachThe study adopted an explanatory sequential mixed method of which the quantitative data were collected first and then analysis was performed. Then, the results of quantitative data were used to plan for the collection of qualitative data. The quantitative data were collected from performance audit report while the qualitative data were collected using semi-structured interviews.FindingsThe study identified six (6) general latent shortcomings and twenty-one (21) detailed latent shortcomings. The general latent shortcomings were inadequate planning and designing of the project; inappropriate adhering to the procurement procedures for materials; inadequate contract supervision; lack of qualified personnel to execute and supervise the works; lack of appropriate equipment and tools; and improper recording of cost of materials, labour and overheads in the books of accounts.Research limitations/implicationsThe research focused on the force account construction approach as applied in the Tanzania context.Practical implicationsThe research stresses that policymakers and practitioners are required to evaluate critically the scope and application of the force account mechanism. The force account procedures should be made based on the nature, scope, magnitude and thresholds of the project. The procuring organisations should ensure that the cost–benefit analysis is undertaken before implementing the force account projects. The findings of this study can be used as inputs to the present laws, regulations and guidelines related to the force account projects.Social implicationsThe present study has the potentials to the communities of which force account projects are undertaken. It stresses that the force account method offers employments opportunity to the social communities.Originality/valueThe study has identified the latent shortcomings of the projects implemented under the force account method. This topic has received attention in Tanzania and developing countries. The study can be credited for its implications to policymakers, practitioners and communities including its emphasis on conducting a cost–benefit analysis.
The development of posture supporting soft exosuit design for adolescent idiopathic scoliosis
Authors: Cakmak Sukran , Cegindir Nese Yasar , Yilmaz Hurriyet Gursel 
Published: October 2021

PurposeAdolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine. Orthoses are the most commonly used treatment material in AIS. However, the physiological and psychological problems that arise due to these orthoses' rigid structures prevent their use by patients. Due to these problems, the authors have developed a posture supporting garment (soft exosuit) design for individuals aged 10–18, with Cobb angles of 25°–40°, which is the most rapidly progressing stage of the disease.Design/methodology/approachSoft exosuit prepared with experimental research method and user-centered design approach. The posture supporting effect is achieved by pattern engineering using fabric, belts, baleens and a gradual zipper system for to increase functionality, ease of use and fit.FindingsThe first six-month clinical trial in prototype use was carried out with a female patient with a 29° scoliosis Cobb angle and suitable wearing a rigid corset due to AIS. The patient was satisfied with the prototype and its functionality, ease of use, fit and comfort. Cosmetic body deformity due to scoliosis was not observed, and the Cobb angle was decreased by 10.7% at the end of the sixth month. Soft exosuit has been found effective in supporting the posture of individuals who had ongoing spinal growth.Research limitations/implicationsThe most important limitation of this study is that, despite a large number of prototype and prototype studies, trials could not be conducted on a large number of patients with different characteristics due to the COVID-19 pandemic. More experimental studies are needed to generalize the product to large audiences. The first goal is to investigate more patients with different spinal deformities in the future. The second goal is to measure the materials used and the quantitative measurement of body responses with the biomechanics field. It is planned to increase the soft exosuit functionality with smart textiles by adding wearable devices with future research.Practical implicationsThis study is important because it constitutes the basis for future studies on pattern cutting soft materials' positioning.Social implicationsIt is thought that the study will contribute to functional solutions for different spinal deformities.Originality/valueIt is an entire functional soft garment without an actuator. It is customizable and modular for patients with spinal deformities. It is thought that the study will contribute to functional solutions for spinal deformities.
Web analytics: more than website performance evaluation?
Authors: Önder Irem , Berbekova Adiyukh 
Published: October 2021

Purpose
The purpose of this study is to understand the status quo of the use of Web analytics tools by European destination management organizations (DMOs) and to provide guidelines in using these metrics for business intelligence and tourism design. In addition, the goal is to improve destination management at the city level using Web analytics data.

Design/methodology/approach
In this exploratory study, the authors analyze how European DMOs view Web analytics data through the lens of the “data to knowledge to results” framework. The authors analyze the use of Web analytics tools by DMOs through the theory of affordances and “data-to-knowledge framework” developed by Davenport et al., which incorporates several factors that contribute to a successful transformation of data available to an organization to knowledge, desirable results and ultimately to building an analytical capability.

Findings
The results show that European DMOs mainly use Web analytics data for website quality assurance, but that some are also using them to drive marketing programs. The study concludes by providing several suggestions for ways in which DMOs might optimize the use of Web analytics data, which will also improve the management of destinations.

Originality/value
Web analytics tools are used by many organizations such as DMOs to collect traffic data, to evaluate and optimize websites. However, these metrics can also be combined with other data such as bednights numbers and used for forecasting or other managerial decisions for destination management at the city level. There is a research gap in this area that focuses on using Web analytics data for business intelligence in the tourism industry and this research aims to fill this gap.
Numerical and experimental study on dynamic characteristics of tilting-pad journal bearings considering pivot stiffness in a vertical rotor system
Authors: Zhang Fan , Yin Peng , Liu Yuyang , Wang Jianmei 
Published: October 2021

Purpose
The purpose of this paper is to study the influence of pivot stiffness on the dynamic characteristics of tilting-pad journal bearings (TPJBs) and the stability of the bearing-rotor system.

Design/methodology/approach
A theoretical numerical model is established, and the influences of pivot stiffness on TPJBs and a bearing-rotor system are analyzed. Then, two kinds of pivot structures with different stiffness are designed and the vibration characteristics are tested on the vertical rotor bearing test bench.

Findings
The pivot stiffness has an obvious effect on the dynamic characteristics of the TPJBs and the stability of the bearing-rotor system. As a result of appropriate pivot stiffness, the critical speed and the vibration amplification factor can be reduced, the logarithmic decay rate and the stability of the rotor system can be effectively increased. While the journal whirl orbit is smoother and the rubbing is obviously reduced when the bearings have flexible pivots.

Originality/value
The influence of pivot stiffness on TPJBs and a vertical rotor-bearing system is studied by theoretical and experimental methods.
Effects of Al2O3 mass fraction on microstructure and friction–wear performance of laser cladded Fe90 alloy coating
Authors: Hu Yan , Kong Dejun 
Published: October 2021

Purpose
This paper aims to improve the friction reduction and wear resistance of Fe90 alloy coating by the addition of Al2O3.

Design/methodology/approach
Fe90 alloy coatings with the different Al2O3 mass fractions were prepared on Q235 steel by laser cladding (LC). The morphologies, phases and hardness of Fe90 alloy coating were analyzed using a scanning electron microscope (SEM), X-ray diffraction (XRD) and microhardness tester, respectively. The effects of Al2O3 mass fraction on the coefficient of friction (COF) and wear rates of Fe90 alloy coating were investigated using a friction tester, and the wear model was built to discuss the wear mechanism of Al2O3-reinforced Fe90 alloy coating.

Findings
The results show that the large number of Fe carbides is generated on the Fe90–Al2O3 coatings by the effect of laser high energy, and the hardness of Fe90–coating is 806 HV0.5, which is 4.48 times of substrate. The average COFs of Fe90–Al2O3 alloy coatings decrease from 0.73 to 0.55, and the wear rates are also reduced from 447.78 to 274.63 µm3•s–1•N–1 by the addition of Al2O3. The Fe90–6% Al2O3 coating presents the highest wear resistance among the three kinds of coatings, and the wear mechanism is abrasive wear and micro-cutting wear.

Originality/value
The Al2O3-reinforced Fe90 alloy coating was first fabricated by laser cladding, and the effect of Al2O3 on the friction-wear performance of Fe90 alloy coating was investigated.