bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of fluorophore brightness in designed mini fluorescence activating proteins
Authors: Hostetter Emma R. , Keyes Jeffrey R. , Poon Ivy , Nguyen Justin P. , Nite Jacob ,   Molecular Modeling and Design Class, Jimenez Hoyos Carlos A. , Smith Colin A. 
Published: July 2021

AbstractThe de novo computational design of proteins with predefined three-dimensional structure is becoming much more routine due to advancements both in force fields and algorithms. However, creating designs with functions beyond folding is more challenging. In that regard, the recent design of small beta barrel proteins that activate the fluorescence of an exogenous small molecule chromophore (DFHBI) is noteworthy. These proteins, termed mini Fluorescence Activating Proteins (mFAPs), have been shown increase the brightness of the chromophore more than 100-fold upon binding to the designed ligand pocket. The design process created a large library of variants with different brightness levels but gave no rational explanation for why one variant was brighter than another. Here we use quantum mechanics and molecular dynamics simulations to investigate how molecular flexibility in the ground and excited states influences brightness. We show that the ability of the protein to resist dihedral angle rotation of the chromophore is critical for predicting brightness. Our simulations suggest that the mFAP/DFHBI complex has a rough energy landscape, requiring extensive ground-state sampling to achieve converged predictions of excited-state kinetics. While computationally demanding, this roughness suggests that mFAP protein function can be enhanced by reshaping the energy landscape towards states that better resist DFHBI bond rotation.
CoverageMaster: comprehensive CNV detection and visualization from NGS short reads for genetic medicine applications
Authors: Rapti Melivoia , Meylan Jenny , Ranza Emmanuele , Antonarakis Stylianos E. , Santoni Federico A. 
Published: July 2021

AbstractCoverageMaster (CoM) is a Copy Number Variation (CNV) calling algorithm based on depth-of-coverage maps designed to detect CNVs of any size in exome (WES) and genome (WGS) data. The core of the algorithm is the compression of sequencing coverage data in a multiscale Wavelet space and the analysis through an iterative Hidden Markov Model (HMM). CoM processes WES and WGS data at nucleotide scale resolution and accurately detect and visualize full size range CNVs, including single or partial exon deletions and duplications. The results obtained with this approach support the possibility for coverage-based CNV callers to replace probe-based methods such array CGH and MLPA in the near future.
Change in Plasma Alpha-Tocopherol Associations with Attenuated Pulmonary Function Decline and with CYP4F2 Missense Variation
Authors: Xu Jiayi , Guertin Kristin A. , Gaddis Nathan C. , Agler Anne H. , Parker Robert S. , Feldman Jared M. , Kristal Alan R. , Arnold Kathryn B. , Goodman Phyllis J. , Tangen Catherine M. , Hancock Dana B. , Cassano Patricia A. 
Published: July 2021

AbstractBackgroundGiven its antioxidant activity, vitamin E is hypothesized to attenuate the age-related decline in pulmonary function.ObjectiveWe investigated the association between change in plasma vitamin E (ΔvitE) and pulmonary function decline and examined genetic and non-genetic factors associated with ΔvitE.DesignWe studied 1,144 men randomized to vitE in the Selenium and Vitamin E Cancer Prevention Trial. ΔvitE was calculated as the difference between baseline and year 3 vitE concentrations measured with gas chromatography-mass spectrometry. Pulmonary function (forced expiratory volume in the first second [FEV1]) was measured longitudinally with spirometry. We genotyped 555 participants (vitE-only arm) using the Illumina MEGAex array. We examined the association of ΔvitE with annual change in FEV1 using mixed-effects linear regression. We also examined the association of previously reported genetic and non-genetic factors with ΔvitE.ResultsGreater ΔvitE was associated with attenuated FEV1 decline, with stronger effects in adherent supplement responders: a 1 SD higher ΔvitE (+4 µmol/mmol free-cholesterol-adjusted α-tocopherol) attenuated FEV1 decline by ∼8.9 mL/year (P=0.014). This effect size is ∼1/4 of the effect of one year of aging, but in the opposite direction. The ΔvitE-FEV1 association was positive in never and current smokers (9.7 and 11.0 mL/year attenuated FEV1 decline, respectively), but there was little to no association in former smokers. Greater ΔvitE was associated with lower baseline α-tocopherol, higher baseline γ-tocopherol, higher baseline free cholesterol, European ancestry (vs. African ancestry) (all P<0.0001), and the minor allele of a missense variant in CYP4F2 (rs2108622-T) (2.4 µmol/L greater ΔvitE; P=0.0032).ConclusionsGreater response to vitE supplementation was associated with attenuated FEV1 decline, and this response was differed by rs2108622 such that individuals with the C allele may need a higher vitE intake dose to reach the same plasma level, compared to the T allele.
Systematic Review and Meta-analysis of Eculizumab, Inebilizumab, Tocilizumab, and Satralizumab for Neuromyelitis Optica
Authors: Chamlagain Rajan , Shah Sangam , Gaire Suman , Paudel Anuj Krishna , Dahal Krishna , kandel Bipin , Dhital Roman , Paudel Basanta Sharma , Dhakal Sandesh , Basnet Madan 
Published: July 2021

AbstractNeuromyelitis optica is rare, autoimmune-mediated inflammation and demyelination of the central nervous system with a prevalence of 1-2 persons per 100,000 populations. We aim to generate a head-to-head comparison of these drugs with appropriate evidence to guide future trials and treatment guidelines in a patient with recurrent attacks of NMO. We searched the databases like PubMed, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase for studies published prior to April 2021 using the keywords. Over all 929 patients from 11 different publications were included in the study. Five studies were included for quantitative synthesis. Pooling of studies showed significant mean reduction of ARR in the monoclonal antibody group (-0.26 [-0.35, -0.17], P <0.00001, I2=0%) and the mean difference in EDSS score from baseline in monoclonal antibodies was - 0.23(95% CI [-0.43, -0.03], P=0.02, I2=0%). There was no significant difference in frequency of total reported adverse events between monoclonal antibody and the comparator arm (RR: 1.01 [0.95, 1.07], P=0.74, I2=14%). Our findings, particularly seen from the context of a few RCTs, support the pursuit of larger, multi-center RCTs that evaluate the effectiveness of each of the currently available monoclonal antibodies and better describe their adverse risk profile.
Assessing target engagement using proteome-wide solvent shift assays
Authors: Van Vranken Jonathan G. , Li Jiaming , Navarrete-Perea José , Gygi Steven P. 
Published: July 2021

AbstractRecent advances in mass spectrometry (MS) have enabled quantitative proteomics to become a powerful tool in the field of drug discovery, especially when applied toward proteome-wide target engagement studies. Similar to temperature gradients, increasing concentrations of organic solvents stimulate unfolding and precipitation of the cellular proteome. This property can be influenced by physical association with ligands and other molecules, making individual proteins more or less susceptible to solvent-induced denaturation. Herein, we report the development of proteome-wide solvent shift assays by combining the principles of solvent-induced precipitation (Zhang et al., 2020) with modern quantitative proteomics. Using this approach, we developed solvent proteome profiling (SPP), which is capable of establishing target engagement through analysis of SPP denaturation curves. We readily identified the specific targets of compounds with known mechanisms of action. As a further efficiency boost, we applied the concept of area-under-the-curve analysis to develop solvent proteome integral solubility alteration (solvent-PISA) and demonstrate that this approach can serve as a reliable surrogate for SPP. We propose that by combining SPP with alternative methods, like thermal proteome profiling, it will be possible to increase the absolute number of high-quality melting curves that are attainable by either approach individually thereby increasing the fraction of the proteome that can be screened for evidence of ligand binding.
Conformation and membrane interaction studies of the potent antimicrobial and anticancer peptide palustrin-Ca
Authors: Timmons Patrick B. , Hewage Chandralal M. 
Published: July 2021

AbstractPalustrin-Ca (GFLDIIKDTGKEFAVKILNNLKCKLAGGCPP) is a host defense peptide with potent antimicrobial and anticancer activities, first isolated from the skin of the American bullfrogLithobates catesbeianus. The peptide is 31 amino acid residues long, cationic and amphipathic. Two-dimensional NMR spectroscopy was employed to characterise its three-dimensional structure in a 50/50% water/2,2,2-trifluoroethanol-d3mixture. The structure is defined by anα-helix that spans between Ile6-Ala26, and a cyclic disulphide bridged domain at the C-terminal end of the peptide sequence, between residues 23 and 29.A molecular dynamics simulation was employed to model the peptide’s interactions with sodium dodecyl sulphate micelles, a widely used bacterial membrane-mimicking environment. Throughout the simulation, the peptide was found to maintain itsα-helical conformation between residues Ile6-Ala26, while adopting a position parallel to the surface to micelle, which is energetically-favourable due to many hydrophobic and electrostatic contacts with the micelle.
Quantification of archaea-driven freshwater nitrification: from single cell to ecosystem level
Authors: Klotz Franziska , Kitzinger Katharina , Ngugi David Kamanda , Büsing Petra , Littmann Sten , Kuypers Marcel M. M. , Schink Bernhard , Pester Michael 
Published: July 2021

AbstractDeep oligotrophic lakes sustain large archaeal populations of the class Nitrososphaeria in their hypolimnion. They are thought to be the key ammonia oxidizers in these freshwater systems and as such responsible for the rate-limiting step in nitrification. However, the impact that planktonic Nitrososphaeria have on N cycling in lakes is severely understudied and yet to be quantified. Here, we followed this archaeal population in one of Central Europe’s largest lakes, Lake Constance, over two consecutive years using metagenomics and metatranscriptomics combined with stable isotope-based activity measurements. A single, highly abundant and transcriptionally active freshwater ecotype of Nitrososphaeria dominated the nitrifying community. Phylogenomic analysis of its metagenome-assembled genome showed that this ecotype represents a new lacustrine Nitrosopumilus species. Stable isotope probing revealed that Nitrososphaeria incorporated significantly more 15N-labeled ammonium than most other microorganisms at near-natural conditions and oxidized ammonia at an average rate of 0.22 ± 0.11 fmol cell−1 d−1. This translates to 1.9 gigagram of ammonia oxidized per year, corresponding to 12% of the N-biomass produced annually by photosynthetic organisms in Lake Constance. Here, we show that ammonia-oxidizing archaea play an equally important role in the nitrogen cycle of deep oligotrophic lakes as their counterparts in marine ecosystems.
GM1 mediates the formation and maintenance of cytotoxic Aβ oligomers
Authors: Zhang Dong Yan , Wang Jian , Fleeman Rebecca M. , Kuhn Madison K. , Swulius Matthew T. , Proctor Elizabeth A. , Dokholyan Nikolay V. 
Published: July 2021

ABSTRACTThe aggregation of amyloid beta (Aβ) peptide is associated with Alzheimer’s disease (AD) pathogenesis. Cell membrane composition, especially monosialotetrahexosylganglioside (GM1), is known to promote the formation of Aβ fibrils, yet little is known about the roles of GM1 in the early steps of Aβ oligomer formation. Here, by using GM1-contained liposomes as a mimic of neuronal cell membrane, we demonstrate that GM1 is a critical trigger of Aβ oligomerization and aggregation. We find that GM1 not only promotes the formation of Aβ fibrils, but also facilitates the maintenance of Aβ oligomers on liposome membranes. We structurally characterize the Aβ oligomers formed on the membrane and find that GM1 captures Aβ by binding to its arginine-5 residue. To interrogate the mechanism of Aβ oligomer toxicity, we design a new liposome-based Ca2+-encapsulation assay and provide new evidence for the Aβ ion channel hypothesis. Finally, we conduct cell viability assay to determine the toxicity of Aβ oligomers formed on membranes. Overall, by uncovering the roles of GM1 in mediating early Aβ oligomer formation and maintenance, our work provides a novel direction for pharmaceutical research for AD.
Impact of socioeconomic development on inflation in South Asia: evidence from panel cointegration analysis
Authors: Islam Md. Saiful 
Published: July 2021

Purpose
This study aims to examine the influence of socioeconomic development on inflation in South Asia using the foreign exchange rate and money supply as control variables.

Design/methodology/approach
The study uses annual panel data for five South Asian economies, namely, Bangladesh, India, Nepal, Pakistan and Sri Lanka over the period 1990–2018, applies cointegrating regression techniques, namely, the panel dynamic ordinary least square (OLS) and fully modified OLS estimators to examine the long-run relations and conducts the Toda-Yamamoto Granger causality test to detect the direction of causality among variables.

Findings
The cointegrating regression estimations have documented that the socioeconomic development proxied by the human development index (HDI) has no significant impact on inflation. Although economic development represented by gross domestic product (GDP) growth causes inflation, socioeconomic development represented by HDI has no impact on inflation and has demonstrated as a better macroeconomic indicator, and thus creates no inflationary pressure in the economy. The foreign exchange rate has a positive impact on inflation. The broad money supply has the usual positive effect on domestic inflation that endorses the monetarist view about prices. The Toda-Yamamoto Granger causality test has confirmed several unidirectional causalities: inflation causes HDI, money supply causes both inflation and HDI and the foreign exchange rate causes HDI.

Practical implications
The study has practical implications for policymakers in South Asia, to improve HDI, particularly GDP per capita, education and health-care facilities to realize continuous socioeconomic development, which will take care of inflation. Moreover, these counties may follow a conservative monetary policy to control inflationary pressure in their economies.

Originality/value
The study is original and claims to be the first to examine the impact of socioeconomic development on inflation. The findings have socioeconomic values regarding controlling inflation in South Asia.
Geomagnetic orbit determination: EKF or UKF?
Authors: Wu Jin , Liu Ming , Zhang Chengxi , Huang Yulong , Zhou Zebo 
Published: July 2021

Purpose
Autonomous orbit determination using geomagnetic measurements is an important backup technique for safe spacecraft navigation with a mere magnetometer. The geomagnetic model is used for the state estimation of orbit elements, but this model is highly nonlinear. Therefore, many efforts have been paid to developing nonlinear filters based on extended Kalman filter (EKF) and unscented Kalman filter (UKF). This paper aims to analyze whether to use UKF or EKF in solving the geomagnetic orbit determination problem and try to give a general conclusion.

Design/methodology/approach
This paper revisits the problem and from both the theoretical and engineering results, the authors show that the EKF and UKF show identical estimation performances in the presence of nonlinearity in the geomagnetic model.

Findings
While EKF consumes less computational time, the UKF is computationally inefficient but owns better accuracy for most nonlinear models. It is also noted that some other navigation techniques are also very similar with the geomagnetic orbit determination.

Practical implications
The intrinsic reason of such equivalence is because of the orthogonality of the spherical harmonics which has not been discovered in previous studies. Thus, the applicability of the presented findings are not limited only to the major problem in this paper but can be extended to all those schemes with spherical harmonic models.

Originality/value
The results of this paper provide a fact that there is no need to choose UKF as a preferred candidate in orbit determination. As UKF achieves almost the same accuracy as that of EKF, its loss in computational efficiency will be a significant obstacle in real-time implementation.
Factors influencing customers' continuance usage intention of food delivery apps during COVID-19 quarantine in Mexico
Authors: Ramos Karen 
Published: July 2021

PurposeThe aim of this study was to find out the factors that influenced customers' continuance usage intention of food delivery apps (FDAs) during COVID-19 quarantine.Design/methodology/approachThe information was obtained by applying an online survey to a sample of 295 residents in Tijuana, Mexico, who were repeat customers of the FDAs during COVID-19 quarantine. Exploratory factor analysis (EFA), the average variance explained (AVE) and composite reliability (CR) were conducted to ensure the validity of each construct. Multiple regression analysis was done to identify predictors of customers' continuance usage intention.FindingsBased on the Unified Theory of Acceptance and Use of Technology 2 (UTAUT-2), four constructs were included: effort expectancy, performance expectancy, food and beverage quality and price saving orientation. Multiple linear regressions were carried out to assess the relationship between the four dimensions and customers' continuance usage intention of FDAs. The results obtained show that effort expectancy, performance expectancy and price saving orientation influenced the customers' continuous usage behavior.Originality/valueThis study contributes to the body of knowledge on consumer behavior on the continuance usage intention of FDAs during the COVID-19 pandemic, which has been scarcely studied. Also, the food and beverage quality construct was proposed, and the price value construct from the UTAUT-2 theory was adapted to price saving orientation.
Consumers' willingness to pay for food safety attributes of tomato
Authors: Joya Khalid , Ramli Nurul Nadia , Shamsudin Mad Nasir , Kamarulzaman Nitty Hirawaty 
Published: July 2021

PurposeConsumers are giving greater attention to the selection of food due to the improvement in income and urbanization. Meanwhile, in recent years, the vegetables' farmers in Malaysia have been reported using an excessive quantity of pesticides. The vegetables exported to Singapore and China have been rejected in 2018 and 2017 due to the presence of excessive levels of pesticides. Such incidences have created massive concern to improve the safety standard of the vegetable industry. The purpose of this paper is to evaluate consumers' willingness to pay for food safety attributes of tomato.Design/methodology/approachDiscrete choice experiments has been used, and 490 respondents have completed the survey.FindingsResults suggested that consumers were willing to pay RM4.18 more for wholesome tomato relative to slightly damage tomato. Consumers also were willing to pay RM2.75 more for organic tomato relative to inorganic tomato. They were also willing to pay RM2.30 and RM1.29 more for certified and tomato sold at supermarket relative to uncertified and tomato sold at the wet market, respectively. The willingness to pay for safety attributes of tomato also varied according to the income, age and education level of the consumers.Research limitations/implicationsIf the farmers can respond effectively to the changes in consumers demand, it can be translated into business opportunities.Originality/valueThis research able to provide relevant information related to the consumers' willingness to pay for food safety attributes of tomato in Malaysia.
Work-family conflict and project performance of construction professionals in a developing country: testing the mediating–moderating effect of project management self-efficacy
Authors: Novieto Divine Tuinese , Kportufe Gladstone Sena 
Published: July 2021

PurposeWork-family conflict (WFC), a common problem in all sectors of every economy, has always been linked to negative consequences for individuals, families and employment organisations. However, owing to contextual and situational differences coupled with inconsistent findings, more studies on WFC are indispensable to disentangle the consequential effects of WFC, especially amongst construction professionals. More so, little is known about the dual role of project management self-efficacy (PMSE) in the WFC-performance relation. Thus, the purpose of the present study is to examine the mediating-moderating effects of PMSE on the WFC-performance nexus amongst construction professionals in a developing economy.Design/methodology/approachData for this study came from a cross-sectional survey (questionnaire) administered to 302 construction professionals in Ghana using convenience sampling technique. And partial least square-based structural equation modelling (PLS-SEM) was performed, which included the assessment of measurement and structural models.FindingsThe results of this study support the mediating–moderating model of WFC, in which PMSE simultaneously mediates and moderates the negative influence of WFC on project performance of construction professionals; thus, validating the dual role of PMSE through the lens of Hobfoll's (1989) conservation of resource theory.Research limitations/implicationsData were collected from a conveniently sampled construction professionals in Ghana. Thus, the sampling framework, including only the construction professionals in three regions of Ghana, does not ensure the full generalisation of the results.Practical implicationsThe findings of the study provide significant implication for construction organisations and practitioners. Construction organisations and practitioners seeking to mitigate the negative consequences of WFC on project performance should focus on building on PMSE of the construction professionals. Further, a responsive work environment is needed to cater for family needs of the construction professionals.Originality/valueThis paper is one of the first to have tested a model including the mediating-moderating effects of PMSE in the construction industry from a developing country perspective. The study, therefore, enriches the prevailing literature from under-represented context by examining the mediating-moderating effects of PMSE on WFC and project performance nexus that has not been previously investigated.