bluuebunny/crossref_metadata_2025_split huggingface dataset:
New machine learning and physics-based scoring functions for drug discovery
Authors: Guedes Isabella A. , Barreto André M. S. , Marinho Diogo , Krempser Eduardo , Kuenemann Mélaine A. , Sperandio Olivier , Dardenne Laurent E. , Miteva Maria A. 
Published: February 2021

AbstractScoring functions are essential for modern in silico drug discovery. However, the accurate prediction of binding affinity by scoring functions remains a challenging task. The performance of scoring functions is very heterogeneous across different target classes. Scoring functions based on precise physics-based descriptors better representing protein–ligand recognition process are strongly needed. We developed a set of new empirical scoring functions, named DockTScore, by explicitly accounting for physics-based terms combined with machine learning. Target-specific scoring functions were developed for two important drug targets, proteases and protein–protein interactions, representing an original class of molecules for drug discovery. Multiple linear regression (MLR), support vector machine and random forest algorithms were employed to derive general and target-specific scoring functions involving optimized MMFF94S force-field terms, solvation and lipophilic interactions terms, and an improved term accounting for ligand torsional entropy contribution to ligand binding. DockTScore scoring functions demonstrated to be competitive with the current best-evaluated scoring functions in terms of binding energy prediction and ranking on four DUD-E datasets and will be useful for in silico drug design for diverse proteins as well as for specific targets such as proteases and protein–protein interactions. Currently, the MLR DockTScore is available at www.dockthor.lncc.br.
O antigen restricts lysogenization of non-O157 Escherichia coli strains by Stx-converting bacteriophage phi24B
Authors: Golomidova A. K. , Efimov A. D. , Kulikov E. E. , Kuznetsov A. S. , Belalov I. Sh. , Letarov A. V. 
Published: February 2021

AbstractAcquisition of new prophages that are able to increase the bacterial fitness by the lysogenic conversion is believed to be an important strategy of bacterial adaptation to the changing environment. However, in contrast to the factors determining the range of bacteriophage lytic activity, little is known about the factors that define the lysogenization host range. Bacteriophage phi24B is the paradigmal model of Stx-converting phages, encoding the toxins of the Shiga-toxigenic E. coli (STEC). This virus has been shown to lysogenize a wide range of E. coli strains that is much broader than the range of the strains supporting its lytic growth. Therefore, phages produced by the STEC population colonizing the small or large intestine are potentially able to lysogenize symbiotic E. coli in the hindgut, and these secondary lysogens may contribute to the overall patient toxic load and to lead to the emergence of new pathogenic STEC strains. We demonstrate, however, that O antigen effectively limit the lysogenization of the wild E. coli strains by phi24B phage. The lysogens are formed from the spontaneous rough mutants and therefore have increased sensitivity to other bacteriophages and to the bactericidal activity of the serum if compared to their respective parental strains.
The switching mechanisms of social network densification
Authors: Kobayashi Teruyoshi , Génois Mathieu 
Published: February 2021

AbstractDensification and sparsification of social networks are attributed to two fundamental mechanisms: a change in the population in the system, and/or a change in the chances that people in the system are connected. In theory, each of these mechanisms generates a distinctive type of densification scaling, but in reality both types are generally mixed. Here, we develop a Bayesian statistical method to identify the extent to which each of these mechanisms is at play at a given point in time, taking the mixed densification scaling as input. We apply the method to networks of face-to-face interactions of individuals and reveal that the main mechanism that causes densification and sparsification occasionally switches, the frequency of which depending on the social context. The proposed method uncovers an inherent regime-switching property of network dynamics, which will provide a new insight into the mechanics behind evolving social interactions.
Blood lead level and risk of hypertension in the United States National Health and Nutrition Examination Survey 1999–2016
Authors: Tsoi Man Fung , Lo Chris Wai Hang , Cheung Tommy Tsang , Cheung Bernard Man Yung 
Published: February 2021

AbstractLead is a heavy metal without a biological role. High level of lead exposure is known to be associated with hypertension, but the risk at low levels of exposure is uncertain. In this study, data from US NHANES 1999–2016 were analyzed. Adults with blood lead and blood pressure measurements, or self-reported hypertension diagnosis, were included. If not already diagnosed, hypertension was defined according to the AHA/ACC 2017 hypertension guideline. Results were analyzed using R statistics version 3.5.1 with sample weight adjustment. Logistic regression was used to study the association between blood lead level and hypertension. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated. Altogether, 39,477 participants were included. Every doubling in blood lead level was associated with hypertension (OR [95%CI] 1.45 [1.40–1.50]), which remained significant after adjusting for demographics. Using quartile 1 as reference, higher blood lead levels were associated with increased adjusted odds of hypertension (Quartile 4 vs. Quartile 1: 1.22 [1.09–1.36]; Quartile 3 vs. Quartile 1: 1.15 [1.04–1.28]; Quartile 2 vs. Quartile 1: 1.14 [1.05–1.25]). In conclusion, blood lead level is associated with hypertension in the general population with blood lead levels below 5 µg/dL. Our findings suggest that reducing present levels of environmental lead exposure may bring cardiovascular benefits by reducing blood pressure.
Direct synthesis of nanostructured silver antimony sulfide powders from metal xanthate precursors
Authors: Alharbi Yasser T. , Alam Firoz , Salhi Abdelmajid , Missous Mohamed , Lewis David J. 
Published: February 2021

AbstractSilver(I) ethylxanthate [AgS2COEt] (1) and antimony(III) ethylxanthate [Sb(S2COEt)3] (2) have been synthesised, characterised and used as precursors for the preparation of AgSbS2 powders and thin films using a solvent-free melt method and spin coating technique, respectively. The as-synthesized AgSbS2 powders were characterized by powder X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy. The crystalline AgSbS2 powder was investigated using XRD, which shows that AgSbS2 has cuboargyrite as the dominant phase, which was also confirmed by Raman spectroscopy. SEM was also used to study the morphology of the resulting material which is potentially nanostructured. EDX spectra gives a clear indication of the presence of silver (Ag), antimony (Sb) and sulfur (S) in material, suggesting that decomposition is clean and produces high quality AgSbS2 crystalline powder, which is consistent with the XRD and Raman data. Electronic properties of AgSbS2 thin films deposited by spin coating show a p-type conductivity with measured carrier mobility of 81 cm2 V−1 s−1 and carrier concentration of 1.9 × 1015 cm−3. The findings of this study reveal a new bottom-up route to these compounds, which have potential application as absorber layers in solar cells.
C. elegans electrotaxis behavior is modulated by heat shock response and unfolded protein response signaling pathways
Authors: Taylor Shane K. B. , Minhas Muhammad H. , Tong Justin , Selvaganapathy P. Ravi , Mishra Ram K. , Gupta Bhagwati P. 
Published: February 2021

AbstractThe nematodeC. elegansis a leading model to investigate the mechanisms of stress-induced behavioral changes coupled with biochemical mechanisms. Our group has previously characterizedC. elegansbehavior using a microfluidic-based electrotaxis device, and showed that worms display directional motion in the presence of a mild electric field. In this study, we describe the effects of various forms of genetic and environmental stress on the electrotactic movement of animals. Using exposure to chemicals, such as paraquat and tunicamycin, as well as mitochondrial and endoplasmic reticulum (ER) unfolded protein response (UPR) mutants, we demonstrate that chronic stress causes abnormal movement.Additionally, we report thatpqe-1(human RNA exonuclease 1 homolog) is necessary for the maintenance of multiple stress response signaling and electrotaxis behavior of animals. Further, exposure ofC. elegansto several environmental stress-inducing conditions revealed that while chronic heat and dietary restriction caused electrotaxis speed deficits due to prolonged stress, daily exercise had a beneficial effect on the animals, likely due to improved muscle health and transient activation of UPR. Overall, these data demonstrate that the electrotaxis behavior of worms is susceptible to cytosolic, mitochondrial, and ER stress, and that multiple stress response pathways contribute to its preservation in the face of stressful stimuli.
Macroporous chitosan/methoxypoly(ethylene glycol) based cryosponges with unique morphology for tissue engineering applications
Authors: Kumar Pradeep , Pillay Viness , Choonara Yahya E. 
Published: February 2021

AbstractThree-dimensional porous scaffolds are widely employed in tissue engineering and regenerative medicine for their ability to carry bioactives and cells; and for their platform properties to allow for bridging-the-gap within an injured tissue. This study describes the effect of various methoxypolyethylene glycol (mPEG) derivatives (mPEG (-OCH3 functionality), mPEG-aldehyde (mPEG-CHO) and mPEG-acetic acid (mPEG-COOH)) on the morphology and physical properties of chemically crosslinked, semi-interpenetrating polymer network (IPN), chitosan (CHT)/mPEG blend cryosponges. Physicochemical and molecular characterization revealed that the –CHO and –COOH functional groups in mPEG derivatives interacted with the –NH2 functionality of the chitosan chain. The distinguishing feature of the cryosponges was their unique morphological features such as fringe thread-, pebble-, curved quartz crystal-, crystal flower-; and canyon-like structures. The morphological data was well corroborated by the image processing data and physisorption curves corresponding to Type II isotherm with open hysteresis loops. Functionalization of mPEG had no evident influence on the macro-mechanical properties of the cryosponges but increased the matrix strength as determined by the rheomechanical analyses. The cryosponges were able to deliver bioactives (dexamethasone and curcumin) over 10 days, showed varied matrix degradation profiles, and supported neuronal cells on the matrix surface. In addition, in silico simulations confirmed the compatibility and molecular stability of the CHT/mPEG blend compositions. In conclusion, the study confirmed that significant morphological variations may be induced by minimal functionalization and crosslinking of biomaterials.
The power of community science to quantify ecological interactions in cities
Authors: Putman Breanna J. , Williams Riley , Li Enjie , Pauly Gregory B. 
Published: February 2021

AbstractStudying animals in urban environments is especially challenging because much of the area is private property not easily accessible to professional scientists. In addition, collecting data on animals that are cryptic, secretive, or rare is also challenging due to the time and resources needed to amass an adequate dataset. Here, we show that community science can be a powerful tool to overcome these challenges. We used observations submitted to the community science platform iNaturalist to assess predation and parasitism across urbanization gradients in a secretive, ‘hard-to-study’ species, the Southern Alligator Lizard (Elgaria multicarinata). From photographs, we quantified predation risk by assessing tail injuries and quantified parasitism by counting tick loads on lizards. We found that tail injuries increased with age and with urbanization, suggesting that urban areas are risky habitats. Conversely, parasitism decreased with urbanization likely due to a loss of hosts and anti-tick medications used on human companion animals. This community science approach generated a large dataset on a secretive species rapidly and at an immense spatial scale that facilitated quantitative measures of urbanization (e.g. percent impervious surface cover) as opposed to qualitative measures (e.g. urban vs. rural). We therefore demonstrate that community science can help resolve ecological questions that otherwise would be difficult to address.
Microbial degradation of Procion Red by Pseudomonas stutzeri
Authors: Bera Sweta Parimita , Tank S. K. 
Published: February 2021

AbstractThe bacterium Pseudomonas stutzeri SPM-1, obtained from textile wastewater dumping sites of Surat, Gujarat was studied for the degradation of the textile azo dye Procion Red—H3B. The optimization was carried on the phenanthrene enrichment medium followed by exposing it to variable environmental factors and nutritional sources. The complete decolorization of dye (50 mg/L) happened within 20 h of incubation at pH 8 and temperature 32 ± 0.2 °C under microaerophilic conditions. Decolourization was monitored with the shifting of absorbance peak in UV–Vis spectrophotometry and HPLC analysis. The physicochemical studies of effluent before and after the treatment revealed 85%, 90%, and 65% decline in BOD, COD, and TOC levels. The strain showed significant activities of azoreductase (95%), laccase (76%), and NADH-DCIP reductase (88%) at 12 h, 10 h, and 8 h of growth respectively indicating evidence for reductive cleavage of the dye. The changes in the functional groups were confirmed by the presence of new peaks in FT-IR data. GC–MS analysis helped in recognizing the degraded dye compounds thus elucidating the proposed pathway for degradation of Procion Red—H3B. The potential of the bioremediation process was concluded by a phytotoxicity test using two plants, Vigna radiata and Cicer arietinum. Our study demonstrates that the strain Pseudomonas stutzeri SPM-1 has rapid decolorization efficiency and holds a noteworthy perspective in industrial application for textile wastewater treatment.
DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice
Authors: Szurgot Inga , Hanke Leo , Sheward Daniel J. , Vidakovics Laura Perez , Murrell Ben , McInerney Gerald M. , Liljeström Peter 
Published: February 2021

AbstractThe outbreak of the SARS-CoV-2 virus and its rapid spread into a global pandemic made the urgent development of scalable vaccines to prevent coronavirus disease (COVID-19) a global health and economic imperative. Here, we characterized and compared the immunogenicity of two alphavirus-based DNA-launched self-replicating (DREP) vaccine candidates encoding either SARS-CoV-2 spike glycoprotein (DREP-S) or a spike ectodomain trimer stabilized in prefusion conformation (DREP-Secto). We observed that the two DREP constructs were immunogenic in mice inducing both binding and neutralizing antibodies as well as T cell responses. Interestingly, the DREP coding for the unmodified spike turned out to be more potent vaccine candidate, eliciting high titers of SARS-CoV-2 specific IgG antibodies that were able to efficiently neutralize pseudotyped virus after a single immunization. In addition, both DREP constructs were able to efficiently prime responses that could be boosted with a heterologous spike protein immunization. These data provide important novel insights into SARS-CoV-2 vaccine design using a rapid response DNA vaccine platform. Moreover, they encourage the use of mixed vaccine modalities as a strategy to combat SARS-CoV-2.
Improved prediction and characterization of anticancer activities of peptides using a novel flexible scoring card method
Authors: Charoenkwan Phasit , Chiangjong Wararat , Lee Vannajan Sanghiran , Nantasenamat Chanin , Hasan Md. Mehedi , Shoombuatong Watshara 
Published: February 2021

AbstractAs anticancer peptides (ACPs) have attracted great interest for cancer treatment, several approaches based on machine learning have been proposed for ACP identification. Although existing methods have afforded high prediction accuracies, however such models are using a large number of descriptors together with complex ensemble approaches that consequently leads to low interpretability and thus poses a challenge for biologists and biochemists. Therefore, it is desirable to develop a simple, interpretable and efficient predictor for accurate ACP identification as well as providing the means for the rational design of new anticancer peptides with promising potential for clinical application. Herein, we propose a novel flexible scoring card method (FSCM) making use of propensity scores of local and global sequential information for the development of a sequence-based ACP predictor (named iACP-FSCM) for improving the prediction accuracy and model interpretability. To the best of our knowledge, iACP-FSCM represents the first sequence-based ACP predictor for rationalizing an in-depth understanding into the molecular basis for the enhancement of anticancer activities of peptides via the use of FSCM-derived propensity scores. The independent testing results showed that the iACP-FSCM provided accuracies of 0.825 and 0.910 as evaluated on the main and alternative datasets, respectively. Results from comparative benchmarking demonstrated that iACP-FSCM could outperform seven other existing ACP predictors with marked improvements of 7% and 17% for accuracy and MCC, respectively, on the main dataset. Furthermore, the iACP-FSCM (0.910) achieved very comparable results to that of the state-of-the-art ensemble model AntiCP2.0 (0.920) as evaluated on the alternative dataset. Comparative results demonstrated that iACP-FSCM was the most suitable choice for ACP identification and characterization considering its simplicity, interpretability and generalizability. It is highly anticipated that the iACP-FSCM may be a robust tool for the rapid screening and identification of promising ACPs for clinical use.
Revealing noncollinear magnetic ordering at the atomic scale via XMCD
Authors: Kielgast Fridtjof , Baev Ivan , Beeck Torben , Pressacco Federico , Martins Michael 
Published: February 2021

AbstractMass-selected V and Fe monomers, as well as the heterodimer$${\text{Fe}}_1{\text{V}}_1$$Fe1V1, were deposited on a Cu(001) surface. Their electronic and magnetic properties were investigated via X-ray absorption (XAS) and X-ray magnetic circular dichroism (XMCD) spectroscopy. Anisotropies in the magnetic moments of the deposited species could be examined by means of angle resolving XMCD, i.e. changing the X-ray angle of incidence. A weak adatom-substrate-coupling was found for both elements and, using group theoretical arguments, the ground state symmetries of the adatoms were determined. For the dimer, a switching from antiparallel to parallel orientation of the respective magnetic moments was observed. We show that this is due to the existence of a noncollinear spin-flop phase in the deposited dimers, which could be observed for the first time in such a small system. Making use of the two magnetic sublattices model, we were able to find the relative orientations for the dimer magnetic moments for different incidence angles.
The dynamics of explore–exploit decisions reveal a signal-to-noise mechanism for random exploration
Authors: Feng Samuel F. , Wang Siyu , Zarnescu Sylvia , Wilson Robert C. 
Published: February 2021

AbstractGrowing evidence suggests that behavioral variability plays a critical role in how humans manage the tradeoff between exploration and exploitation. In these decisions a little variability can help us to overcome the desire to exploit known rewards by encouraging us to randomly explore something else. Here we investigate how such ‘random exploration’ could be controlled using a drift-diffusion model of the explore–exploit choice. In this model, variability is controlled by either the signal-to-noise ratio with which reward is encoded (the ‘drift rate’), or the amount of information required before a decision is made (the ‘threshold’). By fitting this model to behavior, we find that while, statistically, both drift and threshold change when people randomly explore, numerically, the change in drift rate has by far the largest effect. This suggests that random exploration is primarily driven by changes in the signal-to-noise ratio with which reward information is represented in the brain.
GNSS total variometric approach: first demonstration of a tool for real-time tsunami genesis estimation
Authors: Ravanelli Michela , Occhipinti Giovanni , Savastano Giorgio , Komjathy Attila , Shume Esayas B. , Crespi Mattia 
Published: February 2021

AbstractGlobal Navigation Satellite System (GNSS) is used in seismology to study the ground displacements as well as to monitor the ionospheric total electron content (TEC) perturbations following seismic events. The aim of this work is to combine these two observations in one real-time method based on the Total Variometric Approach (TVA) to include the GNSS real-time data stream in future warning systems and tsunami genesis estimation observing both, ground motion and TEC. Our TVA couples together the Variometric Approach for Displacement Analysis Stand-alone Engine (VADASE) with the Variometric Approach for Real-Time Ionosphere Observation (VARION) algorithms. We apply the TVA to the Mw 8.3 Illapel earthquake, that occurred in Chile on September 16, 2015, and we demonstrate the coherence of the earthquake ground shaking and the TEC perturbation by using the same GNSS data stream in a real-time scenario. Nominally, we also highlight a stronger kinetic energy released in the north of the epicenter and visible in both, the ground motion and the TEC perturbation detect at 30 s and around 9.5 min after the rupture respectively. The high spatial resolution of ionospheric TEC measurement seems to match with the extent of the seismic source. The GNSS data stream by TVA of both the ground and ionospheric measurement opens today new perspectives to real-time warning systems for tsunami genesis estimation.