bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic Landscape of HIV Infection in Primary Human Macrophage
Authors: Lu Fang , Yi Yanjie , Vladimirova Olga , Zhankharia Urvi , Collman Ronald G. , Lieberman Paul M. 
Published: January 2022

AbstractHIV-infected macrophages are long-lived cells that sustain persistent virus expression, which is both a barrier to viral eradication and contributor to neurological complications in patients despite antiretroviral therapy (ART). To better understand the regulation of HIV in macrophages, we compared HIV infected primary human monocyte derived macrophages (MDM) to acutely infected primary CD4 T cells and Jurkat cells latently infected with HIV (JLAT 8.4). HIV genomes in MDM were actively transcribed despite enrichment with heterochromatin-associated H3K9me3 across the complete HIV genome in combination with elevated activation marks of H3K9ac and H3K27ac at the LTR. Macrophage patterns contrasted with JLAT cells, which showed conventional bivalent H3K4me3/H3K27me3, and acutely infected CD4 T cells, which showed an intermediate epigenotype. 5‘-methylcytosine (5mC) was enriched across the HIV genome in latently infected JLAT cells, while 5‘-hydroxymethylcytosine (5hmc) was enriched in CD4 and MDM. HIV infection induced multinucleation of MDMs along with DNA damage associate p53 phosphorylation, as well as loss of TET2 and the nuclear redistribution of 5-hydoxymethylation. Taken together, our findings suggest that HIV induces a unique macrophage nuclear and transcriptional profile, and viral genomes are maintained in a non-canonical bivalent epigenetic state.ImportanceMacrophages serve as a reservoir for long-term persistence and chronic production of HIV. We found an atypical epigenetic control of HIV in macrophages marked by heterochromatic H3K9me3 despite active viral transcription. HIV infection induced changes in macrophage nuclear morphology and epigenetic regulatory factors. These findings may identify new mechanisms to control chronic HIV expression in infected macrophage.
A quantitative model for the dynamics of target recognition and off-target rejection by the CRISPR-Cas Cascade complex
Authors: Rutkauskas Marius , Songailiene Inga , Irmisch Patrick , Kemmerich Felix E. , Sinkunas Tomas , Siksnys Virginijus , Seidel Ralf 
Published: January 2022

SUMMARYCRISPR-Cas effector complexes recognise nucleic acid targets by base pairing with their crRNA which enables easy re-programming of the target specificity in rapidly emerging genome engineering applications. However, undesired recognition of off-targets, that are only partially complementary to the crRNA, occurs frequently and represents a severe limitation of the technique. Off-targeting lacks comprehensive quantitative understanding and prediction. Here, we present a detailed analysis of the target recognition dynamics by the Cascade surveillance complex on a set of mismatched DNA targets using single-molecule supercoiling experiments. We demonstrate that the observed dynamics can be quantitatively modelled as a random walk over the length of the crRNA-DNA hybrid using a minimal set of parameters. The model accurately describes the recognition of targets with single and double mutations providing an important basis for quantitative off-target predictions. Importantly the model intrinsically accounts for observed bias regarding the position and the proximity between mutations and reveals that the seed length for the initiation of target recognition is controlled by DNA supercoiling rather than the Cascade structure.
Discovery of S-217622, a Non-Covalent Oral SARS-CoV-2 3CL Protease Inhibitor Clinical Candidate for Treating COVID-19
Authors: Unoh Yuto , Uehara Shota , Nakahara Kenji , Nobori Haruaki , Yamatsu Yukiko , Yamamoto Shiho , Maruyama Yuki , Taoda Yoshiyuki , Kasamatsu Koji , Suto Takahiro , Kouki Kensuke , Nakahashi Atsufumi , Kawashima Sho , Sanaki Takao , Toba Shinsuke , Uemura Kentaro , Mizutare Tohru , Ando Shigeru , Sasaki Michihito , Orba Yasuko , Sawa Hirofumi , Sato Akihiko , Sato Takafumi , Kato Teruhisa , Tachibana Yuki 
Published: January 2022

AbstractThe coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths and threatens public health and safety. Despite the rapid global spread of COVID-19 vaccines, effective oral antiviral drugs are urgently needed. Here, we describe the discovery of S-217622, the first oral non-covalent, non-peptidic SARS-CoV-2 3CL protease inhibitor clinical candidate. S-217622 was discovered via virtual screening followed by biological screening of an in-house compound library, and optimization of the hit compound using a structure-based drug-design strategy. S-217622 exhibited antiviral activity in vitro against current outbreaking SARS-CoV-2 variants and showed favorable pharmacokinetic profiles in vivo for once-daily oral dosing. Furthermore, S-217622 dose-dependently inhibited intrapulmonary replication of SARS-CoV-2 in mice, indicating that this novel non-covalent inhibitor could be a potential oral agent for treating COVID-19.
Comprehensive fitness landscape of SARS-CoV-2 Mpro reveals insights into viral resistance mechanisms
Authors: Flynn Julia M. , Samant Neha , Schneider-Nachum Gily , Barkan David T. , Yilmaz Nese Kurt , Schiffer Celia A. , Moquin Stephanie A. , Dovala Dustin , Bolon Daniel N.A. 
Published: January 2022

AbstractWith the continual evolution of new strains of SARS-CoV-2 that are more virulent, transmissible, and able to evade current vaccines, there is an urgent need for effective anti-viral drugs. SARS-CoV-2 main protease (Mpro) is a leading target for drug design due to its conserved and indispensable role in the viral life cycle. Drugs targeting Mpro appear promising but will elicit selection pressure for resistance. To understand resistance potential in Mpro, we performed a comprehensive mutational scan of the protease that analyzed the function of all possible single amino acid changes. We developed three separate high-throughput assays of Mpro function in yeast, based on either the ability of Mpro variants to cleave at a defined cut-site or on the toxicity of their expression to yeast. We used deep sequencing to quantify the functional effects of each variant in each screen. The protein fitness landscapes from all three screens were strongly correlated, indicating that they captured the biophysical properties critical to Mpro function. The fitness landscapes revealed a non-active site location on the surface that is extremely sensitive to mutation making it a favorable location to target with inhibitors. In addition, we found a network of critical amino acids that physically bridge the two active sites of the Mpro dimer. The clinical variants of Mpro were predominantly functional in our screens, indicating that Mpro is under strong selection pressure in the human population. Our results provide predictions of mutations that will be readily accessible to Mpro evolution and that are likely to contribute to drug resistance. This complete mutational guide of Mpro can be used in the design of inhibitors with reduced potential of evolving viral resistance.
Crystal structure of betaine aldehyde dehydrogenase from Burkholderia pseudomallei
Authors: Beard Dylan K. , Subramanian Sandhya , Abendroth Jan , Dranow David M. , Edwards Thomas E. , Myler Peter J. , Asojo Oluwatoyin A. 
Published: January 2022

Burkholderia pseudomallei infection causes melioidosis, which is often fatal if untreated. There is a need to develop new and more effective treatments for melioidosis. This study reports apo and cofactor-bound crystal structures of the potential drug target betaine aldehyde dehydrogenase (BADH) from B. pseudomallei. A structural comparison identified similarities to BADH from Pseudomonas aeruginosa which is inhibited by the drug disulfiram. This preliminary analysis could facilitate drug-repurposing studies for B. pseudomallei.
Structural and spectroscopic characterization of CO inhibition of [NiFe]-hydrogenase from Citrobacter sp. S-77
Authors: Imanishi Takahiro , Nishikawa Koji , Taketa Midori , Higuchi Katsuhiro , Tai Hulin , Hirota Shun , Hojo Hironobu , Kawakami Toru , Hataguchi Kiriko , Matsumoto Kayoko , Ogata Hideaki , Higuchi Yoshiki 
Published: January 2022

Hydrogenases catalyze the reversible oxidation of H2. Carbon monoxide (CO) is known to be a competitive inhibitor of O2-sensitive [NiFe]-hydrogenases. Although the activities of some O2-tolerant [NiFe]-hydrogenases are unaffected by CO, the partially O2-tolerant [NiFe]-hydrogenase from Citrobacter sp. S-77 (S77-HYB) is inhibited by CO. In this work, the CO-bound state of S77-HYB was characterized by activity assays, spectroscopic techniques and X-ray crystallography. Electron paramagnetic resonance spectroscopy showed a diamagnetic Ni2+ state, and Fourier-transform infrared spectroscopy revealed the stretching vibration of the exogenous CO ligand. The crystal structure determined at 1.77 Å resolution revealed that CO binds weakly to the nickel ion in the Ni–Fe active site of S77-HYB. These results suggest a positive correlation between O2 and CO tolerance in [NiFe]-hydrogenases.
Integrating agriculture and industry 4.0 under “agri-food 4.0” to analyze suitable technologies to overcome agronomical barriers
Authors: Arora Charvi , Kamat Aditya , Shanker Saket , Barve Akhilesh 
Published: January 2022

PurposeThe main intention of this paper is to analyze various factors hindering the growth of the agricultural supply chain and several industry 4.0 technologies to eliminate the same. In addition to a detailed assessment on the implementation of these technologies in agriculture, this manuscript also presents a priority list providing a rank to them based on the relative efficiency of these advancements in addressing these obstacles.Design/methodology/approachThis research proceeds with a two-step process. The particular barriers in the agriculture supply chain and industry 4.0 technologies are determined in the first step. Next, the proposed framework, a combination of data envelopment analysis (DEA) and analytic hierarchy process (AHP), i.e. DEA-AHP, is used to determine a hierarchical structure for the factors and the relative productive efficiencies of the alternatives. The DEA methodology gives a performance analysis of various decision-making units. At the same time, AHP helps in evaluating alternatives weights based on numerous criteria, allowing us to categorize their importance further.FindingsThis study reveals how the involvement of technological advancements in agriculture can help manage the supply chain more efficiently. It also justifies how the large quantities of data generated can handle these increasing challenges in the agricultural supply chain.Practical implicationsThe results of this study provide a priority list of alternatives based on their final weights. This ranking system can help farmers and the government select the best-suited technology for bringing automation into the agricultural supply chain.Originality/valueThis research is unique as it analyes the general factors hindering the development of the agriculture supply chain while simultaneously providing a list of alternatives based on their relative efficiencies. The study enriches existing literature by providing an analytic approach to determine the weightage of various critical success factors that can help improvise and entrust the real and undeniable requirements of consumers, suppliers and producers.
Study on load monitoring and demand side management strategy based on Elman neural network optimized by sparrow search algorithm
Authors: Fan Yuanyuan , Sui Tingyu , Peng Kang , Sang Yingjun , Huang Fei 
Published: January 2022

Purpose
This paper aims to collect the energy consumption data and carry out energy consumption analysis of chemical enterprises, which is helpful to grasp the working conditions of each equipment accurately and to perfect the demand side management (DSM) for the user in the terminal.

Design/methodology/approach
The paper proposes a load monitoring system of chemical enterprises to collect the energy consumption data and carry out energy consumption analysis. An Elman neural network based on sparrow search algorithm is proposed to predict the power consumption change and distribution trend of enterprises in the future production cycle. The calculation efficiency and prediction accuracy have been significantly improved.

Findings
The paper analyzes the energy saving effect of energy efficiency management as well as “avoiding peak and filling valley” measures, and reasonable control requirements and assumed conditions are put forward to study the operability of enterprise energy saving measures from the DSM.

Research limitations/implications
Because of the chosen enterprise data, the prediction accuracy needs to be further improved. Therefore, researchers are encouraged to test the proposed methodology further.

Practical implications
The paper includes implications for the development of energy consumption analysis and load forecasting of chemical enterprises and perfects the DSM for the user.

Originality/value
This paper fulfills an identified need to study how to forecast the power load and improve the management efficiency of energy consumption.
Recognizing workers' construction activities on a reinforcement processing area through the position relationship of objects detected by faster R-CNN
Authors: Li Jiaqi , Zhou Guangyi , Li Dongfang , Zhang Mingyuan , Zhao Xuefeng 
Published: January 2022

PurposeRecognizing every worker's working status instead of only describing the existing construction activities in static images or videos as most computer vision-based approaches do; identifying workers and their activities simultaneously; establishing a connection between workers and their behaviors.Design/methodology/approachTaking a reinforcement processing area as a research case, a new method for recognizing each different worker's activity through the position relationship of objects detected by Faster R-CNN is proposed. Firstly, based on four workers and four kinds of high-frequency activities, a Faster R-CNN model is trained. Then, by inputting the video into the model, with the coordinate of the boxes at each moment, the status of each worker can be judged.FindingsThe Faster R-CNN detector shows a satisfying performance with an mAP of 0.9654; with the detected boxes, a connection between the workers and activities is established; Through this connection, the average accuracy of activity recognition reached 0.92; with the proposed method, the labor consumption of each worker can be viewed more intuitively on the visualization graphics.Originality/valueWith this proposed method, the visualization graphics generated will help managers to evaluate the labor consumption of each worker more intuitively. Furthermore, human resources can be allocated more efficiently according to the information obtained. It is especially suitable for some small construction scenarios, in which the recognition model can work for a long time after it is established. This is potentially beneficial for the healthy operation of the entire project, and can also have a positive indirect impact on structural health and safety.
Brand magnification: when brands help people reconstruct their lives
Authors: Fuschillo Gregorio , Cayla Julien , Cova Bernard 
Published: January 2022

Purpose
This paper aims to detail how consumers can harness the power of brands to reconstruct their lives.

Design/methodology/approach
The authors followed five brand devotees over several years, using various data collection methods (long interviews, observations, videos, photographs and secondary data) to study how they reconstructed their lives with a brand.

Findings
Consumers transform their existence through a distinctive form of brand appropriation that the authors call brand magnification, which unfolds: materially, narratively and socially. First, brand devotees scatter brand incarnations around themselves to remain in touch with the brand because the brand has become an especially positive dimension of their lives. Second, brand devotees mobilize the brand to craft a completely new life story. Finally, they build a branded clan of family and friends that socially validates their reconstructed identity.

Research limitations/implications
The research extends more muted depictions of brands as soothing balms calming consumer anxieties; the authors document the mechanism through which consumers remake their lives with a brand.

Practical implications
The research helps rehabilitate the role of brands in contemporary consumer culture. Organizations can use the findings to help stimulate and engage employees by unveiling the brand’s life-transforming potential for consumers.

Originality/value
The authors characterize a distinctive, extreme and unique form of brand appropriation that positively transforms consumer lives.
Tensions between disciplinarity and generality within a professional development on writing instruction
Authors: Kwok Michelle 
Published: January 2022

PurposeAlthough English Language Arts (ELA) teachers have historically been expected to take the lead in literacy training, the domain of ELA has yet come to terms with what holds it together as a discipline. Within this conundrum, the author studied one group of ELA teacher leaders who led a professional development (PD) aimed at training teachers in disciplinary writing instruction. This study aims to explore the differences in perspectives between what constitutes disciplinarity for ELA teachers and teachers in other content areas.Design/methodology/approachOver the course of two years, the author observed the PD, taking extensive field notes, collecting artifacts and conducting interviews. The author engaged in constant comparative analysis of the data throughout this time, open coding within each data source and then triangulating the data to support the author’s finding.FindingsWhereas the ELA teacher leaders seemed to focus on general aspects of writing, teachers from the other content areas shared discipline-specific understandings about writing. The teachers and teacher leaders, however, did not explicitly discuss these differences in how they conceptualized writing instruction; rather, this tension was revealed through the author’s analysis of the data.Originality/valueThe findings of this study illustrate how a vague definition of writing in English and of disciplinary literacy has come to bear on one PD of writing. This study recommends future research to continue to develop clear epistemologies, purposes and literate practices of the disciplines related to ELA.
The relationship between perceived usability, personality traits and learning gain in an e-learning context
Authors: Vlachogianni Prokopia , Tselios Nikolaos 
Published: January 2022

PurposeThe purpose of this study was to determine the impact of perceived usability and students' personality traits on their learning gain in an e-learning context at the university level.Design/methodology/approachThe factors examined are related to individual characteristics such as students' personality traits, as well as to perceptual characteristics such as the perceived usability of the platform used. A total of 110 undergraduate students participated in the study. A one-group pretest-posttest research design was adopted. Big 5 personality test, System Usability Scale (SUS) and a general knowledge assessment questionnaire were used.FindingsPerceived usability of Zoom platform is statistically significantly correlated with students' learning gain (r = 0.294, p = 0.002, s). Concerning learning effectiveness in the current e-learning scenario, students' final performance was found to be statistically significantly higher than the initial (p = 0.000, s). A hierarchical regression analysis (R2 = 0.146) unveiled that Zoom's perceived usability and personality traits are significant predictors for learning gain (p = 0.011, s).Research limitations/implicationsThe findings of this research provide important implications regarding the design of lessons in an e-learning context.Social implicationsA substantial fraction of the educational process is going online, especially in higher education. Thus, a thorough understanding of the factors which influence learning gain in an e-learning context is of significance.Originality/valueThe main contribution of this study is that it quantifies the variance of the learning gain explained by two factors, namely, SUS and personality.
Millennials’ acceptability of tawarruq-based ar-rahnu in Malaysia
Authors: Amin Hanudin , Hassan M. Kabir 
Published: January 2022

Purpose
This study aims to enlighten the effects of Islamic religiosity, Islamic altruism and Islamic debt collection policy (IDCP) on millennials’ acceptability of tawarruq-based ar-rahnu in Malaysia.

Design/methodology/approach
This study applies the factors drawn from the Islamic theory of consumer behaviour (ITCB) and uses data obtained from a survey of 267 respondents to examine the impact of these factors on millennials’ acceptability of tawarruq-based ar-rahnu.

Findings
The findings indicate that Islamic religiosity, Islamic altruism and IDCP are all important factors influencing millennials’ acceptability of tawarruq-based ar-rahnu.

Research limitations/implications
The study is narrowed down in scope in terms of the broader context of tawarruq-based ar-rahnu and the variables retrieved from the ITCB, which may explain its limited impact.

Practical implications
Considering the effects of the variables investigated in this study might assist enhance product acceptance among consumers.

Originality/value
This study is focussed on tawarruq-based ar-rahnu in the context of the ITCB, taking a different approach than past research on the subject.
Community participation in heritage tourism management of Sukhothai historical park
Authors: Esichaikul Ranee , Chansawang Rochaporn 
Published: January 2022

Purpose
This study aims to examine community participation in cultural heritage management with regard to sustainable heritage tourism management in Sukhothai Historical Park (SHP) in Sukhothai Province.

Design/methodology/approach
The qualitative and quantitative research approaches were applied; in-depth interviews were conducted with 27 key informants, and 104 questionnaires were distributed among stakeholders and local communities.

Findings
The results revealed that sustainable park management has made a positive impact upon local economy, social and cultural conservation of the world heritage site. The Park Authority has developed and conserved archaeological sites with local community assistance, particularly for physical management, but it has not yet used archaeological heritage in the park for more benefits of tourism development.

Research limitations/implications
The results reveal that sustainable park management has made a positive impact on the local economy and social and cultural conservation of the World Heritage city. The Park Authority has developed and conserved archaeological sites with local community assistance, particularly for physical management, but it has not yet used archaeological heritage in the park for greater urban tourism development. Sustainable cultural heritage management in SHP is government-led, so community participation is based upon two-way communication in the form of “tokenism.”

Practical implications
Sukhothai is encouraged to find suitable mechanisms to facilitate multisectoral communication and development to jointly face the challenge of more visitors and urbanization.

Originality/value
Guidelines for enhancing community involvement in cultural heritage management of the park were proposed.