bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-related changes in Tau and Autophagy in human brain in the absence of neurodegeneration
Authors: Chatterjee Shreyasi , Sealey Megan , Ruiz Eva , Pegasiou Chrysia M. , Green Sam , Crisford Anna , Vasquez Michael Duque , Luckett Emma , Robertson Rebecca , Richardson Philippa , Vajramani Girish , Grundy Paul , Bulters Diederik , Proud Christopher , Vargas-Caballero Mariana , Mudher Amritpal 
Published: August 2021

AbstractTau becomes abnormally hyper-phosphorylated and aggregated in tauopathies like Alzheimers disease (AD). As age is the greatest risk factor for developing AD, it is important to understand how tau protein itself, and the pathways implicated in its turnover, change during aging. We investigated age-related changes in total and phosphorylated tau in brain samples from two cohorts of cognitively normal individuals spanning 19-74 years, without overt neurodegeneration. One cohort utilised resected tissue and the other used post-mortem tissue. Total soluble tau levels declined with age in both cohorts. Phosphorylated tau was undetectable in the post-mortem tissue but was clearly evident in the resected tissue and did not undergo significant age-related change. To ascertain if the decline in soluble tau was correlated with age-related changes in autophagy, three markers of autophagy were tested but only two appeared to increase with age and the third was unchanged. This implies that in individuals who do not develop neurodegeneration, there is an age-related reduction in soluble tau which could potentially be due to age-related changes in autophagy. Thus, to explore how an age-related increase in autophagy might influence tau-mediated dysfunctions in vivo, autophagy was enhanced in a Drosophila model and all age-related tau phenotypes were significantly ameliorated. These data shed light on age-related physiological changes in proteins implicated in AD and highlights the need to study pathways that may be responsible for these changes. It also demonstrates the therapeutic potential of interventions that upregulate turnover of aggregate-prone proteins during aging.
Identification and targeting of a pan-genotypic influenza A virus RNA structure that mediates packaging and disease
Authors: Hagey Rachel J. , Elazar Menashe , Tian Siqi , Pham Edward A. , Kladwang Wipapat , Ben-Avi Lily , Nguyen Khanh , Xiong Anming , Rabinovich Meirav , Schaffert Steven , Avisar Talia , Fram Benjamin , Liu Ping , Khatri Purvesh , Taubenberger Jeffery K. , Das Rhiju , Glenn Jeffrey S. 
Published: August 2021

AbstractCurrently approved anti-influenza drugs target viral proteins, are subtype limited, and are challenged by rising antiviral resistance. To overcome these limitations, we sought to identify a conserved essential RNA secondary structure within the genomic RNA predicted to have greater constraints on mutation in response to therapeutics targeting this structure. Here, we identified and genetically validated an RNA stemloop structure we termed PSL2, which serves as a packaging signal for genome segment PB2 and is highly conserved across influenza A virus (IAV) isolates. RNA structural modeling rationalized known packaging-defective mutations and allowed for predictive mutagenesis tests. Disrupting and compensating mutations of PSL2’s structure give striking attenuation and restoration, respectively, of in vitro virus packaging and mortality in mice. Antisense Locked Nucleic Acid oligonucleotides (LNAs) designed against PSL2 dramatically inhibit IAV in vitro against viruses of different strains and subtypes, possess a high barrier to the development of antiviral resistance, and are equally effective against oseltamivir carboxylate-resistant virus. A single dose of LNA administered 3 days after, or 14 days before, a lethal IAV inoculum provides 100% survival. Moreover, such treatment led to the development of strong immunity to rechallenge with a ten-fold lethal inoculum. Together, these results have exciting implications for the development of a versatile novel class of antiviral therapeutics capable of prophylaxis, post-exposure treatment, and “just-in-time” universal vaccination against all IAV strains, including drug-resistant pandemics.One Sentence SummaryTargeting a newly identified conserved RNA structure in the packaging signal region of influenza segment PB2 abrogates virus production in vitro and dramatically attenuates disease in vivo.
Evidence of long-term purging of mutation load in killer whale genomes
Authors: Foote Andrew D. , Gilbert M. Thomas P. , Gopalakrishnan Shyam , Louis Marie , Martin Michael D. , Morin Phillip A. , Nykänen Milaja , Scharff-Olsen Camilla Hjorth , Excoffier Laurent 
Published: August 2021

AbstractGenomes of high latitude killer whales harbour signatures of post-glacial founding and expansion. Here, we investigate whether reduced efficacy of selection increased mutation load in founder populations, or whether recessive deleterious mutations exposed to selection in homozygous genotypes were purged. Comparing the accumulation of synonymous and non-synonymous mutations across pairs of globally sampled genomes reveals that the most significant outliers are high latitude North Atlantic genomes, which have accumulated significantly fewer non-synonymous mutations than all other populations. Comparisons with the genome of a 7.5-Kyr-old North Atlantic killer whale, inferred to be closely related to the population directly ancestral to present-day Icelandic and Norwegian populations, calibrates the timing of the action of selection on non-synonymous mutations predominantly to the mid-late Holocene. Non-synonymous mutations purged in modern Norwegian killer whale genomes are found as globally shared standing variation in heterozygote genotypes more often than expected, suggesting overdominance. Taken together, our findings are consistent with purging of recessive non-synonymous mutations exposed to selection in founder-associated homozygous genotypes.
Integration of whole genome sequencing and transcriptomics reveals a complex picture of insecticide resistance in the major malaria vector Anopheles coluzzii
Authors: Ingham VA , Tennessen JA , Lucas ER , Elg S , Carrington-Yates H , Carson J , Guelbeogo WM , Sagnon N , Hughes G , Heinz E , Neafsey DE , Ranson H 
Published: August 2021

AbstractInsecticide resistance is a major threat to gains in malaria control, which have been stalling and potentially reversing since 2015. Studies into the causal mechanisms of insecticide resistance are painting an increasingly complicated picture, underlining the need to design and implement targeted studies on this phenotype. In this study, we compare three populations of the major malaria vector An. coluzzii: a susceptible and two resistant colonies with the same genetic background. The original colonised resistant population rapidly lost resistance over a 6-month period, a subset of this population was reselected with pyrethroids a third population of this colony that did not lose resistance was also available. The original resistant, susceptible and re-selected colonies were subject to RNAseq and whole genome sequencing, which identified a number of changes across the transcriptome and genome linked with resistance. Firstly, an increase in the expression of genes within the oxidative phosphorylation pathway were seen in both resistant populations compared to the susceptible control; this translated phenotypically through an increased respiratory rate, indicating that elevated metabolism is linked directly with resistance. Genome sequencing highlighted several blocks clearly associated with resistance, including the 2Rb inversion. Finally, changes in the microbiome profile were seen, indicating that the microbial composition may play a role in the resistance phenotype. Taken together, this study reveals a highly complicated phenotype in which multiple transcriptomic, genomic and microbiome changes combine to result in insecticide resistance.
Why be thrifty? Sex-specific heterothermic patterns in wintering captive Microcebus murinus do not translate into differences in energy balance
Authors: Noiret Aude , Karanewsky Caitlin , Aujard Fabienne , Terrien Jeremy 
Published: August 2021

SummaryThe physiological mechanisms of the responses toward stressors are the core of ecophysiology studies to understand the limits of an organism’s flexibility and better predict the impact of environmental degradation on natural populations. However, little information is available when we question inter-individual variability of these physiological responses, even though they can be particularly important. Some observations of intersexual differences in heterothermy raised the question of a difference in energy management between sexes. Here we assess male and female differences in a mouse lemur model (Microcebus murinus), a highly seasonal Malagasy primate, studying their physiological flexibility toward caloric restriction, and examining the impact on their reproductive success. These animals are adapted for naturally changing food availability and climate conditions, and can express deep torpor, allowing them to spare their energy expenses over the dry and cold season. We monitored body mass and body temperature on 12 males and 12 females over winter, applying a chronic 40% caloric restriction to 6 individuals of each group. Our results showed variability of Tb modulations throughout winter and in response to caloric treatment depending on the sex, as females entered deep torpor regardless of food restriction, while only CR males had a similar response. The use of deep torpor, however, did not translate into better body condition either in females, or in response to CR, and did not clearly affect reproductive success. The favorable captive context potentially buffered the depth of torpor and minimized the positive effects of using torpor on energy savings. However, our results may emphasize the existence of other benefits of heterothermic responses than fat reserves.
Beyond dimension reduction: Stable electric fields emerge from and allow representational drift
Authors: Pinotsis Dimitris A. , Miller Earl K. 
Published: August 2021

AbstractIt is known that the exact neurons maintaining a given memory (the neural ensemble) change from trial to trial. This raises the question of how the brain achieves stability in the face of this representational drift. Here, we demonstrate that this stability emerges at the level of the electric fields that arise from neural activity. We show that electric fields carry information about working memory content. The electric fields, in turn, can act as “guard rails” that funnel higher dimensional variable neural activity along stable lower dimensional routes. We obtained the latent space associated with each memory. We then confirmed the stability of the electric field by mapping the latent space to different cortical patches (that comprise a neural ensemble) and reconstructing information flow between patches. Stable electric fields can allow latent states to be transferred between brain areas, in accord with modern engram theory.
Linkages among extended service quality, distinct perceived value and satisfaction in the exhibition trust-building process
Authors: Lee Dae Hui 
Published: August 2021

PurposeThe purpose of this study was to examine the causal relationship between extended service quality including information and communications technology (ICT) and distinct perceived value. This study also examined whether distinct perceived value has different effects on exhibition trust through general attendees' satisfaction.Design/methodology/approachStructural equation modeling was used to examine the causal relationships between the following factors: extended service quality, distinct perceived value, satisfaction and trust.FindingsThe structural relationships between extended service quality, distinct perceived value and satisfaction required to build exhibition trust were empirically confirmed. In particular, ICTs had significant effects on all of the perceived value factors, which reliably supports a conclusion that ICT is a key component of exhibition service quality.Originality/valueRecognizing the significance of ICT, this study has contributed to the field by providing researchers and managers with useful information that not only demonstrates how extended service quality and distinct perceived value independently contribute to satisfaction and interact with each other in doing so but also offers insights for better understanding how trust can be formed in exhibitions. Grasping the distinct preferences for value-oriented activities, understanding the importance of their mediating impacts and expanding the online-offline social networks in which their benefits are promoted and shared can alleviate the uncertainty leading up to exhibition participation while increasing the preemptive transparency of the relationship between quality and value offered by exhibitions.
Strategies to promote collaborative governance regime in Indian rural road maintenance
Authors: Dolla Tharun , Laishram Boeing 
Published: August 2021

PurposeEffective maintenance of rural roads is an essential aspect of public infrastructure delivery. However, governments failed to upkeep the built infrastructure. Accordingly, this study addresses this pressing issue by identifying attributes, skills and resources for asset maintenance. To do this, collaborative governance, a recent plausible alternative in the public policy literature, is used.Design/methodology/approachThe literature review proffered 29 strategies for operationalising collaborative governance principles. A questionnaire survey with the public sector representatives comprising top-level, mid-level and lower-level engineers was used to test the applicability of these strategies in rural infrastructure maintenance of India. The rated responses concerning strategies were subjected to exploratory factor analysis to determine the underlying structure for reducing the dimensions to make them practically operational.FindingsThe exploratory factor analysis showed that six dimensions play an essential role in initiating and promoting collaboration. This parsimonious framework suggests building a common collaborative framework, communicating vision and fostering communities, leadership, increasing the industry's capacity, transparency of power and responsibilities, and technical and financial resources. Thus, governments’ initiatives to build collaboration is most prominent in initiating and sustaining a successful collaboration.Practical implicationsThe practical strategies reinforced through this study can formalise self-initiated regimes or independently convened regimes to a federally directed regime well within the scope of the national programmes. Thus, findings primarily have considerable implications to emerging countries where reducing the unit costs to save the public exchequer from wastage and preventing assets from becoming dilapidate are essential.Originality/valuePublic sector practitioners often lack the essential skills and innovative thinking and thus offered new knowledge would transform the traditional practices in infrastructure maintenance. Theoretically, the present research advances the understanding of structures and processes for collaborative governance theory to non-contractual infrastructure asset management literature.
Revisiting non-convexity in topology optimization of compliance minimization problems
Authors: Abdelhamid Mohamed , Czekanski Aleksander 
Published: August 2021

PurposeThis is an attempt to better bridge the gap between the mathematical and the engineering/physical aspects of the topic. The authors trace the different sources of non-convexification in the context of topology optimization problems starting from domain discretization, passing through penalization for discreteness and effects of filtering methods, and end with a note on continuation methods.Design/methodology/approachStarting from the global optimum of the compliance minimization problem, the authors employ analytical tools to investigate how intermediate density penalization affects the convexity of the problem, the potential penalization-like effects of various filtering techniques, how continuation methods can be used to approach the global optimum and how the initial guess has some weight in determining the final optimum.FindingsThe non-convexification effects of the penalization of intermediate density elements simply overshadows any other type of non-convexification introduced into the problem, mainly due to its severity and locality. Continuation methods are strongly recommended to overcome the problem of local minima, albeit its step and convergence criteria are left to the user depending on the type of application.Originality/valueIn this article, the authors present a comprehensive treatment of the sources of non-convexity in density-based topology optimization problems, with a focus on linear elastic compliance minimization. The authors put special emphasis on the potential penalization-like effects of various filtering techniques through a detailed mathematical treatment.
Information security education based on job profiles and the e-CF
Authors: Spruit Marcel 
Published: August 2021

PurposeThe information security field requires standardised education. This could be based on generic job profiles and a standard competence framework. The question is whether this is possible and feasible. To find out, the author did a case study: developing an information security master curriculum based on a generic PVIB job profile and the underlying competence framework e-CF.Design/methodology/approachThe research is a case study, using Design Science. Starting point is the specification of the learning goals for a cybersecurity master curriculum, using a generic PvIB job profile and the underlying competence framework e-CF. The curriculum has subsequently been developed, using backward design. Thereafter, the curriculum has been submitted for accreditation to test the successfulness of the approach.FindingsA generic job profile and a competence framework such as the e-CF support the development of standardised education. The generic PVIB job profile used works well. The e-CF can be useful, but requires modifications and the introduction of sub-competences. However, the main complaint concerning the e-CF is the use of examples instead of mandatory content.Originality/valueCompetence frameworks are available to formulate job descriptions, and are also suited for developing standardised education. Little research has been done on this. This case study shows that a competence framework is a useful tool for developing standardised education, although the e-CF may not be the most appropriate.
Reducing complexity in multivariate electricity price forecasting
Authors: Kohrs Hendrik , Auer Benjamin Rainer , Schuhmacher Frank 
Published: August 2021

PurposeIn short-term forecasting of day-ahead electricity prices, incorporating intraday dependencies is vital for accurate predictions. However, it quickly leads to dimensionality problems, i.e. ill-defined models with too many parameters, which require an adequate remedy. This study addresses this issue.Design/methodology/approachIn an application for the German/Austrian market, this study derives variable importance scores from a random forest algorithm, feeds the identified variables into a support vector machine and compares the resulting forecasting technique to other approaches (such as dynamic factor models, penalized regressions or Bayesian shrinkage) that are commonly used to resolve dimensionality problems.FindingsThis study develops full importance profiles stating which hours of which past days have the highest predictive power for specific hours in the future. Using the profile information in the forecasting setup leads to very promising results compared to the alternatives. Furthermore, the importance profiles provide a possible explanation why some forecasting methods are more accurate for certain hours of the day than others. They also help to explain why simple forecast combination schemes tend to outperform the full battery of models considered in the comprehensive comparative study.Originality/valueWith the information contained in the variable importance scores and the results of the extensive model comparison, this study essentially provides guidelines for variable and model selection in future electricity market research.
Gender differences in academic entrepreneurship: experience, attitudes and outcomes among NSF I-CORPS participants
Authors: Epstein Alanna , Duval-Couetil Nathalie , Huang-Saad Aileen 
Published: August 2021

PurposeExpanding access to entrepreneurship training programs can be a method to increase female involvement in technology commercialization only if these programs adequately address the specific challenges facing female faculty and graduate students. In the context of the US National Science Foundation's Innovation Corps (NSF I-Corps) program, this study examines gender differences in prior experience and attitudes towards the training in order to propose improvements to the program design.Design/methodology/approachThis quantitative study uses Pearson's Chi-Square and ANOVA tests on survey data from the I-Corps national program (n = 2,195), which enrolls faculty members, graduate students, postdoctoral researchers and industry experts.FindingsIn comparison to male participants, female I-Corps participants reported less entrepreneurial experience prior to the program, poorer team relationships during the program and lower entrepreneurial intention and technology commercialization readiness at both the beginning and the end of the program. However, no gender differences were found in positive or negative perceptions of the instructional climate or perceptions of program usefulness.Originality/valueThis study is unique as it is based on a large-scale dataset drawn from sites across the United States. The results support potential changes to I-Corps and similar programs, including providing more explicit instructions for tasks with which female participants have less prior experience than males (e.g. in applying for patents), offering guidance for team interactions, and providing mentorship to assess whether low self-efficacy is leading women to underestimate the potential success of their projects.
Web-based remote sensing image retrieval using multiscale and multidirectional analysis based on Contourlet and Haralick texture features
Authors: Krishnan Rajakumar , Thangavelu Arunkumar , Prabhavathy P. , Sudheer Devulapalli , Putrevu Deepak , Misra Arundhati 
Published: August 2021

PurposeExtracting suitable features to represent an image based on its content is a very tedious task. Especially in remote sensing we have high-resolution images with a variety of objects on the Earth's surface. Mahalanobis distance metric is used to measure the similarity between query and database images. The low distance obtained image is indexed at the top as high relevant information to the query.Design/methodology/approachThis paper aims to develop an automatic feature extraction system for remote sensing image data. Haralick texture features based on Contourlet transform are fused with statistical features extracted from the QuadTree (QT) decomposition are developed as feature set to represent the input data. The extracted features will retrieve similar images from the large image datasets using an image-based query through the web-based user interface.FindingsThe developed retrieval system performance has been analyzed using precision and recall and F1 score. The proposed feature vector gives better performance with 0.69 precision for the top 50 relevant retrieved results over other existing multiscale-based feature extraction methods.Originality/valueThe main contribution of this paper is developing a texture feature vector in a multiscale domain by combining the Haralick texture properties in the Contourlet domain and Statistical features using QT decomposition. The features required to represent the image is 207 which is very less dimension compare to other texture methods. The performance shows superior than the other state of art methods.