bluuebunny/crossref_metadata_2025_split huggingface dataset:
ColabFold: making protein folding accessible to all
Authors: Mirdita Milot , Schütze Konstantin , Moriwaki Yoshitaka , Heo Lim , Ovchinnikov Sergey , Steinegger Martin 
Published: May 2022

AbstractColabFold offers accelerated prediction of protein structures and complexes by combining the fast homology search of MMseqs2 with AlphaFold2 or RoseTTAFold. ColabFold’s 40−60-fold faster search and optimized model utilization enables prediction of close to 1,000 structures per day on a server with one graphics processing unit. Coupled with Google Colaboratory, ColabFold becomes a free and accessible platform for protein folding. ColabFold is open-source software available at https://github.com/sokrypton/ColabFold and its novel environmental databases are available at https://colabfold.mmseqs.com.
Identifying amyloid-related diseases by mapping mutations in low-complexity protein domains to pathologies
Authors: Murray Kevin A. , Hughes Michael P. , Hu Carolyn J. , Sawaya Michael R. , Salwinski Lukasz , Pan Hope , French Samuel W. , Seidler Paul M. , Eisenberg David S. 
Published: May 2022

AbstractProteins including FUS, hnRNPA2, and TDP-43 reversibly aggregate into amyloid-like fibrils through interactions of their low-complexity domains (LCDs). Mutations in LCDs can promote irreversible amyloid aggregation and disease. We introduce a computational approach to identify mutations in LCDs of disease-associated proteins predicted to increase propensity for amyloid aggregation. We identify several disease-related mutations in the intermediate filament protein keratin-8 (KRT8). Atomic structures of wild-type and mutant KRT8 segments confirm the transition to a pleated strand capable of amyloid formation. Biochemical analysis reveals KRT8 forms amyloid aggregates, and the identified mutations promote aggregation. Aggregated KRT8 is found in Mallory–Denk bodies, observed in hepatocytes of livers with alcoholic steatohepatitis (ASH). We demonstrate that ethanol promotes KRT8 aggregation, and KRT8 amyloids co-crystallize with alcohol. Lastly, KRT8 aggregation can be seeded by liver extract from people with ASH, consistent with the amyloid nature of KRT8 aggregates and the classification of ASH as an amyloid-related condition.
California wildfire spread derived using VIIRS satellite observations and an object-based tracking system
Authors: Chen Yang , Hantson Stijn , Andela Niels , Coffield Shane R. , Graff Casey A. , Morton Douglas C. , Ott Lesley E. , Foufoula-Georgiou Efi , Smyth Padhraic , Goulden Michael L. , Randerson James T. 
Published: May 2022

AbstractChanging wildfire regimes in the western US and other fire-prone regions pose considerable risks to human health and ecosystem function. However, our understanding of wildfire behavior is still limited by a lack of data products that systematically quantify fire spread, behavior and impacts. Here we develop a novel object-based system for tracking the progression of individual fires using 375 m Visible Infrared Imaging Radiometer Suite active fire detections. At each half-daily time step, fire pixels are clustered according to their spatial proximity, and are either appended to an existing active fire object or are assigned to a new object. This automatic system allows us to update the attributes of each fire event, delineate the fire perimeter, and identify the active fire front shortly after satellite data acquisition. Using this system, we mapped the history of California fires during 2012–2020. Our approach and data stream may be useful for calibration and evaluation of fire spread models, estimation of near-real-time wildfire emissions, and as means for prescribing initial conditions in fire forecast models.
Viability, task switching, and fall avoidance of the simplest dynamic walker
Authors: Patil Navendu S. , Dingwell Jonathan B. , Cusumano Joseph P. 
Published: May 2022

AbstractWalking humans display great versatility when achieving task goals, like avoiding obstacles or walking alongside others, but the relevance of this to fall avoidance remains unknown. We recently demonstrated a functional connection between the motor regulation needed to achieve task goals (e.g., maintaining walking speed) and a simple walker’s ability to reject large disturbances. Here, for the same model, we identify the viability kernel—the largest state-space region where the walker can step forever via at least one sequence of push-off inputs per state. We further find that only a few basins of attraction of the speed-regulated walker’s steady-state gaits can fully cover the viability kernel. This highlights a potentially important role of task-level motor regulation in fall avoidance. Therefore, we posit an adaptive hierarchical control/regulation strategy that switches between different task-level regulators to avoid falls. Our task switching controller only requires a target value of the regulated observable—a “task switch”—at every walking step, each chosen from a small, predetermined collection. Because humans have typically already learned to perform such goal-directed tasks during nominal walking conditions, this suggests that the “information cost” of biologically implementing such controllers for the nervous system, including cognitive demands in humans, could be quite low.
Behavioral and inflammatory sex differences revealed by celecoxib nanotherapeutic treatment of peripheral neuroinflammation
Authors: Deal Brooke , Reynolds Laura M. , Patterson Charles , Janjic Jelena M. , Pollock John A. 
Published: May 2022

AbstractNeuropathic pain affects millions of people worldwide, yet the molecular mechanisms of how it develops and persists are poorly understood. Given that males have historically been utilized as the primary sex in preclinical studies, less is known about the female neuroinflammatory response to injury, formation of pain, or response to pain-relieving therapies. Macrophages contribute to the development of neuroinflammatory pain via the activation of their cyclooxygenase-2 (COX-2) enzyme, which leads to the production of prostaglandin E2 (PGE2). PGE2 activates nociception and influences additional leukocyte infiltration. Attenuation of COX-2 activity decreases inflammatory pain, most commonly achieved by nonsteroidal anti-inflammatory drugs (NSAIDs), yet NSAIDs are considered ineffective for neuropathic pain due to off target toxicity. Using chronic constriction injury of the rat sciatic nerve, we show that males and females exhibit quantitatively the same degree of mechanical allodynia post injury. Furthermore, a low-dose nanotherapeutic containing the NSAID celecoxib is phagocytosed by circulating monocytes that then naturally accumulate at sites of injury as macrophages. Using this nanotherapeutic, we show that treated males exhibit complete reversal of hypersensitivity, while the same dose of nanotherapeutic in females provides an attenuated relief. The difference in behavioral response to the nanotherapy is reflected in the reduction of infiltrating macrophages at the site of injury. The observations contained in this study reinforce the notion that female neuroinflammation is different than males.
A noble extended stochastic logistic model for cell proliferation with density-dependent parameters
Authors: Roy Trina , Ghosh Sinchan , Saha Bapi , Bhattacharya Sabyasachi 
Published: May 2022

AbstractCell proliferation often experiences a density-dependent intrinsic proliferation rate (IPR) and negative feedback from growth-inhibiting molecules in culture media. The lack of flexible models with explanatory parameters fails to capture such a proliferation mechanism. We propose an extended logistic growth law with the density-dependent IPR and additional negative feedback. The extended parameters of the proposed model can be interpreted as density-dependent cell-cell cooperation and negative feedback on cell proliferation. Moreover, we incorporate further density regulation for flexibility in the model through environmental resistance on cells. The proposed growth law has similarities with the strong Allee model and harvesting phenomenon. We also develop the stochastic analog of the deterministic model by representing possible heterogeneity in growth-inhibiting molecules and environmental perturbation of the culture setup as correlated multiplicative and additive noises. The model provides a conditional maximum sustainable stable cell density (MSSCD) and a new fitness measure for proliferative cells. The proposed model shows superiority to the logistic law after fitting to real cell culture datasets. We illustrate both conditional MSSCD and the new cell fitness for a range of parameters. The cell density distributions reveal the chance of overproliferation, underproliferation, or decay for different parameter sets under the deterministic and stochastic setups.
The interplay between ranking and communities in networks
Authors: Iacovissi Laura , De Bacco Caterina 
Published: May 2022

AbstractCommunity detection and hierarchy extraction are usually thought of as separate inference tasks on networks. Considering only one of the two when studying real-world data can be an oversimplification. In this work, we present a generative model based on an interplay between community and hierarchical structures. It assumes that each node has a preference in the interaction mechanism and nodes with the same preference are more likely to interact, while heterogeneous interactions are still allowed. The sparsity of the network is exploited for implementing a more efficient algorithm. We demonstrate our method on synthetic and real-world data and compare performance with two standard approaches for community detection and ranking extraction. We find that the algorithm accurately retrieves the overall node’s preference in different scenarios, and we show that it can distinguish small subsets of nodes that behave differently than the majority. As a consequence, the model can recognize whether a network has an overall preferred interaction mechanism. This is relevant in situations where there is no clear “a priori” information about what structure explains the observed network datasets well. Our model allows practitioners to learn this automatically from the data.
Experimental solubility and thermodynamic modeling of empagliflozin in supercritical carbon dioxide
Authors: Sodeifian Gholamhossein , Garlapati Chandrasekhar , Razmimanesh Fariba , Nateghi Hassan 
Published: May 2022

AbstractThe solubility of empagliflozin in supercritical carbon dioxide was measured at temperatures (308 to 338 K) and pressures (12 to 27 MPa), for the first time. The measured solubility in terms of mole faction ranged from 5.14 × 10–6 to 25.9 × 10–6. The cross over region was observed at 16.5 MPa. A new solubility model was derived to correlate the solubility data using solid–liquid equilibrium criteria combined with Wilson activity coefficient model at infinite dilution for the activity coefficient. The proposed model correlated the data with average absolute relative deviation (AARD) and Akaike’s information criterion (AICc), 7.22% and − 637.24, respectively. Further, the measured data was also correlated with 11 existing (three, five and six parameters empirical and semi-empirical) models and also with Redlich-Kwong equation of state (RKEoS) along with Kwak-Mansoori mixing rules (KMmr) model. Among density-based models, Bian et al., model was the best and corresponding AARD% was calculated 5.1. The RKEoS + KMmr was observed to correlate the data with 8.07% (correspond AICc is − 635.79). Finally, total, sublimation and solvation enthalpies of empagliflozin were calculated.
Towards defining biomarkers to evaluate concussions using virtual reality and a moving platform (BioVRSea)
Authors: Jacob Deborah , Unnsteinsdóttir Kristensen Ingunn S. , Aubonnet Romain , Recenti Marco , Donisi Leandro , Ricciardi Carlo , Svansson Halldór Á. R. , Agnarsdóttir Sólveig , Colacino Andrea , Jónsdóttir María K. , Kristjánsdóttir Hafrún , Sigurjónsdóttir Helga Á. , Cesarelli Mario , Eggertsdóttir Claessen Lára Ósk , Hassan Mahmoud , Petersen Hannes , Gargiulo Paolo 
Published: May 2022

AbstractCurrent diagnosis of concussion relies on self-reported symptoms and medical records rather than objective biomarkers. This work uses a novel measurement setup called BioVRSea to quantify concussion status. The paradigm is based on brain and muscle signals (EEG, EMG), heart rate and center of pressure (CoP) measurements during a postural control task triggered by a moving platform and a virtual reality environment. Measurements were performed on 54 professional athletes who self-reported their history of concussion or non-concussion. Both groups completed a concussion symptom scale (SCAT5) before the measurement. We analyzed biosignals and CoP parameters before and after the platform movements, to compare the net response of individual postural control. The results showed that BioVRSea discriminated between the concussion and non-concussion groups. Particularly, EEG power spectral density in delta and theta bands showed significant changes in the concussion group and right soleus median frequency from the EMG signal differentiated concussed individuals with balance problems from the other groups. Anterior–posterior CoP frequency-based parameters discriminated concussed individuals with balance problems. Finally, we used machine learning to classify concussion and non-concussion, demonstrating that combining SCAT5 and BioVRSea parameters gives an accuracy up to 95.5%. This study is a step towards quantitative assessment of concussion.
Sensorless based SVPWM-DTC of AFPMSM for electric vehicles
Authors: Saleh Saber M. , Hassan Amir Y. 
Published: May 2022

AbstractAFPMSM is lighter, has a higher power-to-weight ratio, is shorter in length, is less expensive, and has a higher efficiency than the radial flux motor. Then AFPMSM is more suitable for driving the EV than radial flux motor. The proposed technique in this paper is the sensorless-based SVPWM-DTC of AFPMSM to drive electric vehicles. Sensorless research becomes more important in this circumstance since the axial motor can be placed inside the vehicle tire due to its condensed size and shape similar to the tires. DTC provides less fluctuation for the driver during driving for safety and comfort. SVPWM is preferred for its high performance. When measuring speed using a sensorless estimator, sensor inaccuracy is minimized, and the AFPMS motor can be mounted inside the tire. The control system is tested using two EVs driving cycles, and the results promise high performance. NEDC and HWFET driving cycles are used to test the proposed control scheme in 100 times less than the actual driving cycles’ time to test the coherence of the sensorless estimator. The results demonstrate that the proposed technique is valid for real-time applications with high-performance, minimum torque fluctuations, and minimum transient and steady-state errors.
Stranded because of exhaustion while high-altitude mountaineering in the Swiss Alps: a retrospective nationwide study
Authors: Gasser Benedikt 
Published: May 2022

AbstractFortunately, fatal accidents while high-altitude mountaineering have decreased in recent years, but the number of emergencies has increased. These nonfatal emergencies might represent situations where alpinists are stranded (emergencies in which alpinists are no longer able to continue their tour on their own because of, for example, exhaustion, equipment problems, or weather). We analyzed 4596 cases of high-altitude-mountaineering emergencies in the period 2009 to 2020 from the SAC (Swiss Alpine Club) emergency registry. In total, 1951 cases (41.6%) were due to being stranded, 1348 cases were due to falls (28.7%), and 352 cases were due to illness (7.5%); these were the three most common classes. In cases of being stranded, 90% of alpinists were uninjured or not seriously injured. In addition, we found only eight fatal cases. More than 50% of cases occurred while ascending a summit above 4000 m. The main causes of becoming stranded were exhaustion and weather changes. These findings suggest that alpinists contact rescue organizations before experiencing serious troubles; these situations thus present risks and dangers both to those stranded and to emergency services. Since exhaustion and weather changes are the two main causes, adequate preparation and tour planning may help prevent such emergencies.
Clustering analysis of factors affecting academic career of university students with dyslexia in Italy
Authors: Benedetti Ilaria , Barone Marcella , Panetti Valentina , Taborri Juri , Urbani Tony , Zingoni Andrea , Calabrò Giuseppe 
Published: May 2022

AbstractThis study was designed to explore learning experiences of university students with dyslexia and factors that could contribute to their success in the university career. Although, great efforts have been made to diagnose dyslexia and to mitigate its effects at primary and secondary school, little has been done at the university level in particular in the Italian context. Indeed in the university context, the availability and possibility to use of support tools, that enable the student to achieve educational success, is still not sufficiently adequate. In this paper we used bivariate association tests and cluster analysis, in order to identify the most suitable compensatory tools and support strategies that can facilitate the students’ performance in higher education. The data were obtained through the voluntary participation of Italian students, enrolled in a bachelor degree course, with certified diagnosis of dyslexia. Six groups of students were identified from the cluster analysis, defining specific support tools and learning strategies for each group. Furthermore, through the creation of these six groups, it was possible to describe “profiles” that highlight the risk factors (late diagnosis) and-or protection factors (such as associations, support from friends and family) in analyzing the academic career of students with dyslexia. Therefore, starting from these data, through artificial intelligence it will be possible to identify and suggest study methodologies and create specific support tools for each student that can enable her/him to achieve educational success in her/his academic career.
Genomic determinants of Furin cleavage in diverse European SARS-related bat coronaviruses
Authors: Sander Anna-Lena , Moreira-Soto Andres , Yordanov Stoian , Toplak Ivan , Balboni Andrea , Ameneiros Ramón Seage , Corman Victor , Drosten Christian , Drexler Jan Felix 
Published: May 2022

AbstractThe furin cleavage site (FCS) in SARS-CoV-2 is unique within the Severe acute respiratory syndrome–related coronavirus (SrC) species. We re-assessed diverse SrC from European horseshoe bats and analyzed the spike-encoding genomic region harboring the FCS in SARS-CoV-2. We reveal molecular features in SrC such as purine richness and RNA secondary structures that resemble those required for FCS acquisition in avian influenza viruses. We discuss the potential acquisition of FCS through molecular mechanisms such as nucleotide substitution, insertion, or recombination, and show that a single nucleotide exchange in two European bat-associated SrC may suffice to enable furin cleavage. Furthermore, we show that FCS occurrence is variable in bat- and rodent-borne counterparts of human coronaviruses. Our results suggest that furin cleavage sites can be acquired in SrC via conserved molecular mechanisms known in other reservoir-bound RNA viruses and thus support a natural origin of SARS-CoV-2.
Cortical D1 and D2 dopamine receptor availability modulate methylphenidate-induced changes in brain activity and functional connectivity
Authors: Manza Peter , Shokri-Kojori Ehsan , Demiral Şükrü Barış , Wiers Corinde E. , Zhang Rui , Giddens Natasha , McPherson Katherine , Biesecker Erin , Dennis Evan , Johnson Allison , Tomasi Dardo , Wang Gene-Jack , Volkow Nora D. 
Published: May 2022

AbstractDopamine signaling plays a critical role in shaping brain functional network organization and behavior. Prominent theories suggest the relative expression of D1- to D2-like dopamine receptors shapes excitatory versus inhibitory signaling, with broad consequences for cognition. Yet it remains unknown how the balance between cortical D1R versus D2R signaling coordinates the activity and connectivity of functional networks in the human brain. To address this, we collected three PET scans and two fMRI scans in 36 healthy adults (13 female/23 male; average age 43 ± 12 years), including a baseline D1R PET scan and two sets of D2R PET scans and fMRI scans following administration of either 60 mg oral methylphenidate or placebo (two separate days, blinded, order counterbalanced). The drug challenge allowed us to assess how pharmacologically boosting dopamine levels alters network organization and behavior in association with D1R-D2R ratios across the brain. We found that the relative D1R-D2R ratio was significantly greater in high-level association cortices than in sensorimotor cortices. After stimulation with methylphenidate compared to placebo, brain activity (as indexed by the fractional amplitude of low frequency fluctuations) increased in association cortices and decreased in sensorimotor cortices. Further, within-network resting state functional connectivity strength decreased more in sensorimotor than association cortices following methylphenidate. Finally, in association but not sensorimotor cortices, the relative D1R-D2R ratio (but not the relative availability of D1R or D2R alone) was positively correlated with spatial working memory performance, and negatively correlated with age. Together, these data provide a framework for how dopamine-boosting drugs like methylphenidate alter brain function, whereby regions with relatively higher inhibitory D2R (i.e., sensorimotor cortices) tend to have greater decreases in brain activity and connectivity compared to regions with relatively higher excitatory D1R (i.e., association cortices). They also support the importance of a balanced interaction between D1R and D2R in association cortices for cognitive function and its degradation with aging.
Protocadherin 15 suppresses oligodendrocyte progenitor cell proliferation and promotes motility through distinct signalling pathways
Authors: Zhen Yilan , Cullen Carlie L. , Ricci Raphael , Summers Benjamin S. , Rehman Sakina , Ahmed Zubair M. , Foster Antoinette Y. , Emery Ben , Gasperini Robert , Young Kaylene M. 
Published: May 2022

AbstractOligodendrocyte progenitor cells (OPCs) express protocadherin 15 (Pcdh15), a member of the cadherin superfamily of transmembrane proteins. Little is known about the function of Pcdh15 in the central nervous system (CNS), however, Pcdh15 expression can predict glioma aggression and promote the separation of embryonic human OPCs immediately following a cell division. Herein, we show that Pcdh15 knockdown significantly increases extracellular signal-related kinase (ERK) phosphorylation and activation to enhance OPC proliferation in vitro. Furthermore, Pcdh15 knockdown elevates Cdc42-Arp2/3 signalling and impairs actin kinetics, reducing the frequency of lamellipodial extrusion and slowing filopodial withdrawal. Pcdh15 knockdown also reduces the number of processes supported by each OPC and new process generation. Our data indicate that Pcdh15 is a critical regulator of OPC proliferation and process motility, behaviours that characterise the function of these cells in the healthy CNS, and provide mechanistic insight into the role that Pcdh15 might play in glioma progression.