bluuebunny/crossref_metadata_2025_split huggingface dataset:
ASXL3 controls cortical neuron fate specification through extrinsic self-renewal pathways
Authors: McGrath BT , Wu P , Salvi S , Girgla N , Chen X , Zhu J , KC R , Tsan YC , Moccia A , Srivastava A , Zhou X , Bielas SL 
Published: July 2021

ABSTRACTDuring corticogenesis, transcription plasticity is fundamental to the restriction of neural progenitor cell (NPC) multipotency and production of cortical neuron heterogeneity. Human and mouse genetic studies have highlighted the role of Polycomb transcriptional regulation in this process.ASXL3, which encodes a component of the Polycomb repressive deubiquitination (PR-DUB) complex, has been identified as a high confidence autism spectrum disorder (ASD) risk gene. Genetic inactivation ofAsxl3,in a mouse model that carries a clinically relevantASXL3frameshift (Asxl3fs)variant, disrupts lateral expansion of NPCs and delays cortical neuron differentiation. Single-cell RNA sequencing analysis implicates Notch signaling, which alters the composition of excitatory neurons and fidelity of cortical layer deposition. Our data provides a new link between extrinsic signaling cues and intrinsic epigenetic regulation that together control the timing of cell fate programs. Furthermore, transcriptomic analysis revealed dysregulation of other known ASD risk genes indicating that a convergent developmental pathway is affected. Collectively our work provides important insights about developmental mechanisms that contribute to ASD neuropathology.
Tempo of degeneration across independently evolved non-recombining regions
Authors: Carpentier Fantin , Rodríguez de la Vega Ricardo C. , Jay Paul , Duhamel Marine , Shykoff Jacqui A. , Perlin Michael H. , Wallen R. Margaret , Hood Michael E. , Giraud Tatiana 
Published: July 2021

AbstractRecombination is beneficial over the long term, allowing more effective selection. Despite long-term advantages of recombination, local recombination suppression can evolve and lead to genomic degeneration, in particular on sex chromosomes. Here, we investigated the tempo of degeneration in non-recombining regions, i.e., the function curve for the accumulation of deleterious mutations over time, leveraging on 22 independent events of recombination suppression identified on mating-type chromosomes of anther-smut fungi, including newly identified ones. Using previously available and newly generated high-quality genome assemblies of alternative mating types of 13 Microbotryum species, we estimated degeneration levels in terms of accumulation of non-optimal codons and non-synonymous substitutions in non-recombining regions. We found a reduced frequency of optimal codons in the non-recombining regions compared to autosomes, that was not due to less frequent GC-biased gene conversion or lower ancestral expression levels compared to recombining regions. The frequency of optimal codons rapidly decreased following recombination suppression and reached an asymptote after ca 3 Mya. The strength of purifying selection remained virtually constant at dN/dS = 0.55, i.e. at an intermediate level between purifying selection and neutral evolution. Accordingly, non-synonymous differences between mating-type chromosomes increased linearly with stratum age, at a rate of 0.015 per MY. We thus develop a method for disentangling effects of reduced selection efficacy from GC-biased gene conversion in the evolution of codon usage and we quantify the tempo of degeneration in non-recombining regions, which is important for our knowledge on genomic evolution and on the maintenance of regions without recombination.
Metabolic turnover and dynamics of modified ribonucleosides by 13C labeling
Authors: Gameiro Paulo A. , Encheva Vesela , Dos Santos Mariana Silva , MacRae James I , Ule Jernej 
Published: July 2021

AbstractTandem mass spectrometry (MS/MS) is an accurate tool to assess modified ribonucleosides and their dynamics in mammalian cells. Yet, MS/MS quantification of lowly abundant modifications in non-ribosomal RNAs is unreliable, and the dynamic features of various modifications poorly understood. We developed a 13C labeling approach, 13C-dynamods, to quantify the turnover of base modifications in newly transcribed RNA. This turnover-based approach helped to resolve mRNA from ncRNA modifications in purified RNA or free ribonucleosides, and showed the distinct kinetics of N6-methyladenosine (m62A) versus 7-methylguanosine (m7G) in polyA+-purified RNA. We uncovered that N6,N6-dimethyladenosine (m62A) exhibits a distinct turnover in small RNAs and free ribonucleosides when compared to the known m6 A-modified large rRNAs. Finally, combined measurements of turnover and abundance informed on the transcriptional versus posttranscriptional sensitivity of modified ncRNAs and mRNAs, respectively, to stress conditions. Thus, 13C-dynamods enables studies of origin of modified RNAs at steady-state and their dynamics under non-stationary conditions.
Discovery of nanobodies against SARS-CoV-2 and an uncommon neutralizing mechanism
Authors: Li Tingting , Zhou Bingjie , Luo Zhipu , Lai Yanling , Huang Suqiong , Zhou Yuanze , Gautam Anupriya , Bourgeau Salome , Wang Shurui , Bao Juan , Tan Jingquan , Lavillette Dimitri , Li Dianfan 
Published: July 2021

ABSTRACTSARS-CoV-2 and its variants continue to threaten public health. The virus recognizes the host cell by attaching its Spike receptor-binding domain (RBD) to the host receptor ACE2. Therefore, RBD is a primary target for neutralizing antibodies and vaccines. Here we report the isolation, and biological and structural characterization of two single-chain antibodies (nanobodies, DL4 and DL28) from RBD-immunized alpaca. Both nanobodies bind Spike with affinities that exceeded the detection limit (picomolar) of the biolayer interferometry assay and neutralize the original SARS-CoV- 2 strain with IC50of 0.086 μg mL-1(DL4) and 0.385 μg mL-1(DL28). DL4 and a more potent, rationally designed mutant, neutralizes the Alpha variant as potently as the original strain but only displays marginal activity against the Beta variant. By contrast, the neutralizing activity of DL28, when in the Fc-fused divalent form, was less affected by the mutations in the Beta variant (IC50of 0.414 μg mL-1for Alpha, 1.060 μg mL-1for Beta). Crystal structure studies reveal that DL4 blocks ACE2-binding by direct competition, while DL28 neutralizes SARS-CoV-2 by an uncommon mechanism through which DL28 distorts the receptor-binding motif in RBD and hence prevents ACE2-binding. Our work provides two neutralizing nanobodies for potential therapeutic development and reveals an uncommon mechanism to design and screen novel neutralizing antibodies against SARS-CoV-2.
Discovery of genes that modulate flavivirus replication in an interferon-dependent manner
Authors: Lesage Sarah , Chazal Maxime , Beauclair Guillaume , Batalie Damien , Couderc Elodie , Lescure Aurianne , Del Nery Elaine , Tangy Frédéric , Martin Annette , Manel Nicolas , Jouvenet Nolwenn 
Published: July 2021

AbstractEstablishment of the interferon (IFN)-mediated antiviral state provides a crucial initial line of defense against viral infection. Numerous genes that contribute to this antiviral state remain to be identified. Using a loss-of-function strategy, we screened an original library of 1156 siRNAs targeting 386 individual curated human genes in stimulated microglial cells infected with Zika virus (ZIKV), an emerging RNA virus that belongs to the flavivirus genus. The screen recovered twenty-one potential host proteins that modulate ZIKV replication in an IFN-dependent manner, including the previously known IFITM3 and LY6E. Further characterization contributed to delineate the spectrum of action of these genes towards other pathogenic RNA viruses, including Hepatitis C virus and SARS-CoV-2. Our data revealed that APOL3 acts as a proviral factor for ZIKV and several other related and unrelated RNA viruses. In addition, we showed that MTA2, a chromatin remodeling factor, possesses potent flavivirus-specific antiviral functions. Our work identified previously unrecognized genes that modulate the replication of RNA viruses in an IFN-dependent way, opening new perspectives to target weakness points in the life cycle of these viruses.
Hierarchical clustering optimizes the tradeoff between compositionality and expressivity of task structures for flexible reinforcement learning
Authors: Liu Rex G , Frank Michael J 
Published: July 2021

AbstractA hallmark of human intelligence, but challenging for reinforcement learning (RL) agents, is the ability to compositionally generalise, that is, to recompose familiar knowledge components in novel ways to solve new problems. For instance, when navigating in a city, one needs to know the location of the destination and how to operate a vehicle to get there, whether it be pedalling a bike or operating a car. In RL, these correspond to the reward function and transition function, respectively. To compositionally generalize, these two components need to be transferable independently of each other: multiple modes of transport can reach the same goal, and any given mode can be used to reach multiple destinations. Yet there are also instances where it can be helpful to learn and transfer entire structures, jointly representing goals and transitions, particularly whenever these recur in natural tasks (e.g., given a suggestion to get ice cream, one might prefer to bike, even in new towns). Prior theoretical work has explored how, in model-based RL, agents can learn and generalize task components (transition and reward functions). But a satisfactory account for how a single agent can simultaneously satisfy the two competing demands is still lacking. Here, we propose a hierarchical RL agent that learns and transfers individual task components as well as entire structures (particular compositions of components) by inferring both through a non-parametric Bayesian model of the task. It maintains a factorised representation of task components through a hierarchical Dirichlet process, but it also represents different possible covariances between these components through a standard Dirichlet process. We validate our approach on a variety of navigation tasks covering a wide range of statistical correlations between task components and show that it can also improve generalisation and transfer in more complex, hierarchical tasks with goal/subgoal structures. Finally, we end with a discussion of our work including how this clustering algorithm could conceivably be implemented by cortico-striatal gating circuits in the brain.
Multi-Elemental Isotope And Analog Tracer Application To Measure Nutrient Uptake And Distribution In Malus × Domestica Borkh
Authors: Gomez Raquel , Kalcsits Lee 
Published: July 2021

ABSTRACTPlant nutrient uptake is critical to maintain an optimum balance between vegetative and reproductive growth and fruit quality. Nutrient imbalances, and more specifically the relationship of potassium, magnesium and nitrogen to calcium, can be critical for fruit quality in apple (Malus x domestica Borkh.). In perennial plants, it is difficult to conduct short-term experiments to measure plant uptake and distribution in response to either cultivar or treatment because of substantial preexisting nutrient pools already present. The use of isotopically labeled nitrogen, and nutrient analogs such as strontium and rubidium allow for the quantification of uptake and distribution that is often not possible with bulk mineral analysis. Here, the objective was to understand how scion genotype influences nutrient uptake and partitioning between aboveground and below ground parts of the tree. In this experiment, 10 atom% 15N, Strontium (Sr), and Rubidium (Rb) were applied to three different potted apple cultivars that were either treated with ABA 250 mg/L or 500 mg/L or an untreated control. After 70 days of growth, overall recovery rates of each tracer reflected the mobility of their nutrient analog. Strontium had an average tracer recovery rate of 3.9%, followed by 15N with 14.6% recovery and finally Rb with 15.1%. Independent of treatment, ‘Gala’ significantly absorbed more tracer followed by Granny Smith and Honeycrisp for Rb and Sr but not 15N. These results have implications in understanding the association between aboveground factors like transpiration and nutrient uptake and distribution in apple.
The relationship between the level of a corporation’s public disclosure of its managerial values and its level of organizational authenticity
Authors: Neher Alain , Wong Alfred , Miles Morgan P. 
Published: July 2021

Purpose
This study aims to explore if corporations that publicly disclose more information about their managerial values are also more organizationally authentic in enacting these values.

Design/methodology/approach
A maturity model of managerial values is used that ordinally ranks a corporation’s level of managerial values enactment using corporate annual reports. The samples of corporations’ corporate reports are qualitatively content analyzed, and the outcomes are statistically tested.

Findings
The findings indicate that as an organization voluntarily discloses more information about its corporate values, it tends to be more likely to enact their espoused values, and their corporation’s level of organizational authenticity increases.

Originality/value
This study suggests an approach to benchmark a corporation’s level of organizational authenticity using public information, and by doing so, contributes to both policy and practice by offering a framework to compare organizational authenticity between public corporations by their sector, size or the age of the corporation.
Work environment and performance among nurses: a significant way to overcome violation of human rights in the health sector
Authors: Bhatti Mitho Khan , Soomro Bahadur Ali , Shah Naimatullah 
Published: July 2021

Purpose
The study aims to purpose the role of the work environment (WE) towards employees’ performance (EP) in Pakistan’s health sector.

Design/methodology/approach
Data-wise, the study is cross-sectional and random sampling was used to glean the response from the trained health nurses in Pakistan. The survey questionnaire was used as a primary tool to collect the data. In total, 306 usable samples as used to infer the final consequences.

Findings
The structural equation modeling through AMOS 26.0 for windows resulted in a positive and significant effect of an organizational learning culture, supervisor support on EP. On the other hand, the impact of peer support on EP is not significant among the nurses in Pakistan.

Practical implications
The policymakers and planners in the health sector and government may address unemployment – are willing to join the health sector. Better performance through the WE would provide equity in health and would not violate fundamental human rights. This work may help human resource management bring advancement in organizational and social determinants of health equity and practical interventions to overwhelm health-care barriers.

Originality/value
The study overcomes the gaps in terms of the cross-sectional survey to measure nurses’ performance in Pakistan.
Analysis of lubrication and sealing performance on textured piston pair with multi-factor coupling
Authors: Quan Song , Guo Yong , Liu Xuedong , Chen Zhewu , Liu Yudi 
Published: July 2021

Purpose
This paper aims to study the lubrication and sealing performance on the textured piston pair under the cross action of the shape and structure parameters. This paper further carries out the optimization design of low energy consumption hydraulic impact piston pair.

Design/methodology/approach
Based on the characteristics of the ring gap seal piston pair, the flow field analysis model of the whole film gap is established for its periodic treatment. The friction power loss of the piston pair is defined as the evaluation index of the lubrication performance and the leakage power loss as the evaluation index of the sealing performance. The orthogonal test design and CFD software were used to analyze the lubrication and sealing performance of the textured piston pair.

Findings
The cross action of shape and structure factors has a great influence of the lubrication and sealing performance on the textured piston pair. Clearance and shape parameters have great influence on it, while seal length and depth diameter ratio have little influence. The sealing performance of conical textured piston pair is good, while the lubrication performance of square textured piston pair is good. The primary and secondary order of influence of shape and structure on energy consumption on piston pair is B (seal clearance) > C (texture shape) > D (area ratio) > A (seal length) > E (depth diameter ratio).

Originality/value
Breaking the defect of local optimization design on traditional piston pair structure, then find the matching relationship of structural parameters on textured piston pair. Further improve the lubrication and sealing performance of the piston pair, and provide reference for the global optimization design of the low energy consumption hydraulic impact piston pair.
A simulation-based binomial model for building development appraisal
Authors: Lawal Yarima Sallau , Ibrahim Aliyu Makarfi , Abubakar Mu'awiya , Ishaq Ziyadul Hassan , Sa'ad Mohammed Mustapha 
Published: July 2021

Purpose
Building developments are often capital intensive, have a long payback period and many associated risks and uncertainties. This makes investments in building projects to be a big challenge. This study aims to develop a computerized simulation-based binomial model (CSBBM) for building investment appraisal with a view to improving the economic sustainability of proposed building projects.

Design/methodology/approach
Mathematical equations and algorithms were developed based on the binomial method (BM) of real options analysis and then implemented on a computer system. A hybrid algorithm that integrates Monte Carlo simulation (MCS) and BM was also developed. A real-life project was used to test the model. Sensitivity analysis was also conducted to explore the influence of input variables on development option value (DOV).

Findings
The test result shows that the model developed provides a better estimate of the value of an investment when compared with traditional net present value technique, which underestimate the value. Moreover, inflation rate (i) and rental value (Ri) are the most sensitive variables for DOV. An increase in i and Ri by just 5% causes a corresponding increase in DOV by 202% and 132%, respectively. While the least sensitive variable is the discount rate (r), as an increase in r by 5% causes a corresponding decrease in DOV by just 9%. The CSBBM is capable of determining the optimal time of development of buildings with an accuracy of 80.77%.

Practical implications
The hybrid model produces higher DOV than that of only the BM because MCS considers randomness in uncontrollable variables. Thus, building investment decision-makers should always use MCS to complement the BM in an investment analysis.

Originality/value
There is limited evidence on the use of this kind of hybrid model for determining DOV in practice.
Coordination of similar days and multi-objective posterior process to predict energy of transmission substation
Authors: Abdolrezaei Hassan , Siahkali Hassan , Olamaei Javad 
Published: July 2021

Purpose
This paper aims to present a hybrid model to mid-term forecast the load of transmission substations based on the knowledge of expert site and multi-objective posterior framework. The main important challenges in load forecasting are the different behavior of load in specific days. Regular days, holidays and special holidays, days after a holidays and days of load shifting are characterized by abnormal load profiles. The knowledge of these days is verified by expert operators in regional dispatching centers.

Design/methodology/approach
In this paper, a hybrid model for power prediction of transmission substations based on the combination of similar day selection and multi-objective posterior technique has been proposed. In the first step, the important data for prediction is provided. Posterior method is used in the second step for prediction that it is based on kernel functions. A multi-objective optimization has been formulated with three type of output accuracy measurement function that it is solved by non-dominated sorting genetic technique II (NSGT-II) method. TOPSIS way is used to find the best point of Pareto.

Findings
The presented method has been tested in four scenarios for three different transmission stations, and the test results have been compared. The presented results indicate that the presentation method has better results and is robust to different load characteristics, which can be used for better forecasting of different stations for better planning of repairs and network operation.

Originality/value
The main contributions of this paper can be categorized as follows: A hybrid model based on similar days selection and multi-objective framework posterior is presented. Similar day selection is done by expert site that the day type and days with scheduled repair are considered. Hyperparameters of posterior process are found by NSGT-II based on TOPSIS method.
Effect of non-linear thermal radiation on the stagnation point flow of double diffusive free convection due to movingvertical plate
Authors: Nandeppanavar Mahantesh M. , M.C. Kemparaju , N. Raveendra 
Published: July 2021

Purpose
This paper aims to find the influence of convective heat transfer, buoyancy proportions, nonlinear thermal radiation, Prandtl number, Rayleigh number and Schmidt number on velocity, temperature and concentration profiles.

Design/methodology/approach
This paper explores the heat and mass transfer of a stagnation point stream of free convective Casson fluid over a moving vertical plate with nonlinear thermal radiation and convective boundary restrictions. The governing PDEs of stream, heat and concentration profiles were reformed into an arrangement of nonlinear ODEs by using similarity transformation. This framework was then tackled numerically by applying forth-order RK shooting strategy.

Findings
Distribution of flow, velocity and temperature profiles for different values of governing parameters are analyzed.

Originality/value
The original results are depicted in terms of plots.
Migrant entrepreneurs from an advanced economy in a developing country: the case of Korean entrepreneurs in Malaysia
Authors: Abd Hamid Hamizah , Everett André M. 
Published: July 2021

Purpose
This study aims to explore the co-ethnic relations of migrant entrepreneurs (MEs) from advanced economies in a developing country, specifically in the context of co-ethnic ties among Korean migrant entrepreneurs (KMEs) operating business ventures in Malaysia.

Design/methodology/approach
This research is outlined by an embeddedness view and uses a qualitative approach using a single case study design.

Findings
For KMEs, in-group co-ethnic ties are mobilised in a relatively more structured manner coalescing personal and entrepreneurial endeavours, particularly demonstrating the dynamics of co-ethnic ties and the home country’s development levels. The findings lead to a model of migrant entrepreneurship for MEs from a more developed nation.

Originality/value
The theoretical value of this study lies in its clarification of the role of in-group ties in the setting of changing economic development levels and migration. Practice-wise, the findings on the adoption of co-ethnic ties that span formal, informal and transnational boundaries may inform migrants who are considering opportunities in less developed host countries, and assist stakeholders in developing policies concerning migrant communities and their ventures.