Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of K-Ras4B dimer interfaces and the role of Raf effectors

K-Ras4B is one the most frequently mutated proteins in cancer, yet mechanistic details of its activation such as its homodimerization on the membrane remain elusive. The structural determinants of K-Ras4B homodimerization have been debated with different conformations being proposed in the literature. Here, we perform microsecond all-atom Molecular Dynamics (MD) simulations on the K-Ras4B monomer in solution, the K-Ras4B monomer on the membrane, and two experimentally-based K-Ras4B dimer models of the α4-α5 interface to investigate the stability of these structures bound to GTP on a model cell membrane. We then evaluate the complexes for their propensity to form stable dimers on the plasma membrane in the presence and absence of Raf[RBD–CRD] effectors. We find that Raf[RBD-CRD] effectors enhance dimer stability, suggesting that the presence of effectors is necessary for K-Ras4B dimers stabilization on the cell membrane. Moreover, we observe, for the first time, a dynamic water channel at the K-Ras4B dimer interface, and identify putative allosteric connections in the K-Ras4B dimer interface. To discover novel K-Ras4B interfaces, we perform coarse-grained MD simulations in two dissociated K-Ras4B monomers on the membrane, which reveal that the dominant dimer interface is the α4-α5 interface. Finally, a druggability analysis is performed in the different K-Ras4B structures in the monomeric states. Strikingly, all known binding pockets of K-Ras4B are identified only in the structure that is membrane-bound, but not in the solution structure. Based on these results, we propose that modulating the protein-membrane interactions can be an alternative strategy for inhibiting K-Ras4B signaling.
Alternatives for correcting the Tukey's statistics for unbalanced experiments

Unbalanced experiments are those in which treatments do not have the same number of replications. Some multiple comparison tests need to be correct to behave well in unbalanced situations. For the Tukey test is suggested the use of the harmonic mean of the numbers of replications. The aim of this paper is to verify the performance of the harmonic, arithmetic, weighted, quadratic, and geometric means, the minimum, maximum and median number of repetitions as a correction for the Tukey test, and propose a correction that improves the performance of harmonic mean. We measured the type I error rate and power via Monte Carlo simulation, at 5\% of significance. The harmonic mean performs best but could be improved. The proposal made in this work was capable of controlling the type I error in all cases studied.
Passivity breaking of a local vacuum state in a quantum Hall system

We propose an experimental method for extracting the zero-point energy from a local vacuum state by performing local operations and classical communication (LOCC). We model a quantum Hall edge channel as a quantum entangled many-body channel and the zero-point fluctuation in the charge density of the channel as the vacuum state. We estimate the order of the energy gain using reasonable experimental parameters. Such a quantum feedback system breaks the passivity of a local vacuum state. It can be used to demonstrate Maxwell's demon or quantum energy teleportation in which no physical entity transports energy.
Learning-by-Exporting Eﬀects: Are They for Real?

: We investigate whether exposure to export markets improves plant productivity. Our estimation framework adds export experience as an additional state variable and a fixed cost of entry into export markets to Olley and Pakes’s (1996) behavioral model. We find robust evidence of a positive effect of export experience on productivity, controlling for the bias caused by self-selection of the most productive plants into exporting. The effect is stronger for plants with the most exposure to exporting, and statistically insignificant for exporters that stop exporting. Our analysis also suggests that matching methods may produce upwardly biased estimates of learning-by-exporting effects.
Ensemble Learning with small machine learning algorithms for Network Intrusion Detection

Networks are always vulnerable to unwanted access. Network intrusion detection aims to detect these intruders. Machine learning is a technique that can provide scalable tools to recognise and classify attack patterns, eventually to help deter or defeat certain types of network intrusions. In this thesis, I investigate the possibilities to combine diﬀerent machine learning techniques. In this way, I want to compare the accuracy and improve the impact on the detection rate for the individual attack classes. In the research, I use network data from the KDD99 data set and the CICIDS2017 data set. From these raw data I select features belonging to a certain attack class and train individual models with Naive Bayes learning and Decision Trees. I compare four diﬀerent techniques to combine the individual models. As ensemble methods, I investigate soft voting, hard voting, ANN and Decision Trees. As a result, I found that with soft voting it is possible to increase both the accuracy and the F 1 score for the attack classes with a certain combination of individual models.
The public information needs of COVID-19 vaccine: A study based on online Q&A communities and portals in China

Purpose This study analyzes the topic and distribution features of public information needs for the COVID-19 vaccine from Chinese online Q&A communities and portals. It aims to identify the features and differences in public COVID-19 vaccine information needs at different periods. Design/Methodology A total of 14,296 questions about the COVID-19 vaccine from four Chinese mainstream online communities and portals were studied following five procedures: data collection, data processing, K-means clustering, LDA topic model analysis, and needs identification. Findings The study identified the topical features of public information needs for the COVID-19 vaccine during the first pandemic outbreak, pre-listing period, and post-listing period. It constructed a framework of public vaccine information needs. The information needs can be classified into 8 main categories and 16 subcategories. The eight main categories are vaccination (53.72%), evaluation and impact of other social events (17.90%), vaccine R&D and listing (9.49%), vaccine side effects and countermeasures (5.63%), vaccination necessity (4.98%), vaccine patent exemption (3.26%), vaccination effectiveness (2.94%), and essential knowledge of vaccine (2.08%), where percentage refers to the distribution of information needs data under various categories. Implications Online communities and portals should provide dynamic and tailored information services according to changing public vaccine information needs. The public information needs regarding vaccination is prominent and should be addressed first. In the follow-up booster vaccination efforts, government health departments should prioritize susceptible groups, such as overseas students, airport workers, and healthcare workers. Originality/Value We built a conceptual framework using data mining techniques and analyzed the COVID-19 vaccine information needs distribution at different time points and among different social groups, focusing on the theme of public information needs for the COVID-19 vaccine. It makes recommendations for government health departments and online platforms to improve the quality of COVID-19 vaccine information services for the public and provide a reference for the vaccination of COVID-19 booster shots.
Inequality and risk aversion in economies open to altruistic attitudes

This paper attempts to find a relationship between agents' risk aversion and inequality of incomes. Specifically, a model is proposed for the evolution in time of surplus/deficit distribution, and the long-time distributions are characterized almost completely. They turn out to be weak Pareto laws with exponent linked to the relative risk aversion index which, in turn, is supposed to be the same for every agent. On the one hand, the aforesaid link is expressed by an affine transformation. On the other hand, the level of the relative risk aversion index results from a frequency distribution of observable quantities stemming from how agents interact in an economic sense. Combination of these facts is conducive to the specification of qualitative and quantitative characteristics of actions fit for the control of income concentration.
GeMs/GSAOI observations of La Serena 94: an old and far open cluster inside the solar circle

Physical properties were derived for the candidate open cluster La Serena 94, recently unveiled by the VVV collaboration. Thanks to the exquisite angular resolution provided by GeMS/GSAOI, we could characterize this system in detail, for the first time, with deep photometry in JHK$_{s}$ - bands. Decontaminated JHK$_{s}$ diagrams reach about 5 mag below the cluster turnoff in H. The locus of red clump giants in the colour - colour diagram, together with an extinction law, was used to obtain an average extinction of $A_V =14.18 \pm 0.71$. The same stars were considered as standard - candles to derive the cluster distance, $8.5 \pm 1.0$ kpc. Isochrones were matched to the cluster colour - magnitude diagrams to determine its age, $\log{t(yr)}=9.12\pm 0.06$, and metallicity, $Z=0.02\pm0.01$. A core radius of $r_{c}=0.51\pm 0.04$ pc was found by fitting King models to the radial density profile. By adding up the visible stellar mass to an extrapolated mass function, the cluster mass was estimated as $M=(2.65\pm0.57) \times 10^3$ M$_{\odot}$, consistent with an integrated magnitude of $M_{K}=-5.82\pm0.16$ and a tidal radius of $r_{t}=17.2\pm2.1$ pc. The overall characteristics of La Serena 94 confirm that it is an old open cluster located in the Crux spiral arm towards the fourth Galactic quadrant and distant $7.30\pm 0.49$ kpc from the Galactic centre. The cluster distorted structure, mass segregation and age indicate that it is a dynamically evolved stellar system.
Jingmenviruses: Ubiquitous, understudied, segmented flavi-like viruses

Jingmenviruses are a group of viruses identified recently, in 2014, and currently classified by the International Committee on Taxonomy of Viruses as unclassified Flaviviridae. These viruses closely related to flaviviruses are unique due to the segmented nature of their genome. The prototype jingmenvirus, Jingmen tick virus (JMTV), was discovered in Rhipicephalus microplus ticks collected from China in 2010. Jingmenviruses genomes are composed of four to five segments, encoding for up to seven structural proteins and two non-structural proteins, both of which display strong similarities with flaviviral non-structural proteins (NS2B/NS3 and NS5). Jingmenviruses are currently separated into two phylogenetic clades. One clade includes tick- and vertebrate-associated jingmenviruses, which have been detected in ticks and mosquitoes, as well as in humans, cattle, monkeys, bats, rodents, sheep, and tortoises. In addition to these molecular and serological detections, over a hundred human patients tested positive for jingmenviruses after developing febrile illness and flu-like symptoms in China and Serbia. The second phylogenetic clade includes insect-associated jingmenvirus sequences, which have been detected in a wide range of insect species, as well as in crustaceans, plants, and fungi. In addition to being found in various types of hosts, jingmenviruses are endemic, as they have been detected in a wide range of environments, all over the world. Taken together, all of these elements show that jingmenviruses correspond exactly to the definition of emerging viruses at risk of causing a pandemic, since they are already endemic, have a close association with arthropods, are found in animals in close contact with humans, and have caused sporadic cases of febrile illness in multiple patients. Despite these arguments, the vast majority of published data is from metagenomics studies and many aspects of jingmenvirus replication remain to be elucidated, such as their tropism, cycle of transmission, structure, and mechanisms of replication and restriction or epidemiology. It is therefore crucial to prioritize jingmenvirus research in the years to come, to be prepared for their emergence as human or veterinary pathogens.
Increased risk of sleep-related movement disorder in patients with Helicobacter pylori infection: A nationwide population-based study

Background and purpose Evidence increasingly suggests that Helicobacter pylori infection (HPI) is associated with movement disorders such as Parkinson's disease (PD). However, the relationship between HPI and sleep-related movement disorders (SRMD) remains unknown. This nationwide population-based study tried to demonstrate whether patients with HPI have a higher risk of developing SRMD in a general adult population. Methods The study cohort enrolled 9,393 patients who were initially diagnosed with HPI between 2000 and 2013. Notably, 37,572 age- and sex-matched controls without prior HPI were selected as the reference. A Cox proportional hazard regression analysis was performed for multivariate adjustment. Results Patients with HPI had a higher risk of developing SRMD (adjusted hazard ratio [HR] = 2.18, 95% confidence interval [CI] = 1.26–3.82, p < 0.01). Patients with HPI aged ≥65 years exhibited the highest risk (HR = 3.01, 95% CI = 1.90–5.30, p < 0.001), followed by patients aged 45–64 years (HR = 1.69, 95% CI = 1.26–2.90, p <0.01) and <45 years (HR = 1.49, 95% CI = 1.12–2.49, p < 0.01). Patients were most likely to develop SRMD 5 years or more after diagnosis of HPI (HR = 3.33, 95% CI = 1.97–5.89, p < 0.001). The increased risk of SRMD in male patients with HPI (HR = 2.73, 95% CI = 1.53–4.79, p < 0.001) was greater than in female patients (HR = 1.14, 95% CI = 1.04–1.65, p < 0.05). Conclusion Patients with HPI were associated with an increased risk for SRMD, with a higher risk in men, aged ≥65 years, and diagnosed for more than 5 years.
Latitudinal patterns and environmental drivers of taxonomic, functional, and phylogenetic diversity of woody plants in western Amazonian terra firme forests

Elucidating how environmental factors drive plant species distributions and how they affect latitudinal diversity gradients, remain essential questions in ecology and biogeography. In this study we aimed: 1) to investigate the relationships between all three diversity attributes, i.e., taxonomic diversity (TD), functional diversity (FD), and phylogenetic diversity (PD); 2) to quantify the latitudinal variation in these diversity attributes in western Amazonian terra firme forests; and 3) to understand how climatic and edaphic drivers contribute to explaining diversity patterns. We inventoried ca. 15,000 individuals from ca. 1,250 species, and obtained functional trait records for ca. 5,000 woody plant individuals in 50 plots of 0.1 ha located in five terra firme forest sites spread over a latitudinal gradient of 1200 km covering ca. 10°C in latitude in western Amazonia. We calculated all three diversity attributes using Hill numbers: q = 0 (richness), q = 1 (richness weighted by relative abundance), and q = 2 (richness weighted by dominance). Generalized linear mixed models were constructed for each diversity attribute to test the effects of different uncorrelated environmental predictors comprising the temperature seasonality, annual precipitation, soil pH and soil bulk density, as well as accounting for the effect of spatial autocorrelation, i.e., plots aggregated within sites. We confirmed that TD (q = 0, q = 1, and q = 2), FD (q = 0, q = 1, and q = 2), and PD (q = 0) increased monotonically towards the Equator following the latitudinal diversity gradient. The importance of rare species could explain the lack of a pattern for PD (q = 1 and q = 2). Temperature seasonality, which was highly correlated with latitude, and annual precipitation were the main environmental drivers of variations in TD, FD, and PD. All three diversity attributes increased with lower temperature seasonality, higher annual precipitation, and lower soil pH. We confirmed the existence of latitudinal diversity gradients for TD, FD, and PD in hyperdiverse Amazonian terra firme forests. Our results agree well with the predictions of the environmental filtering principle and the favourability hypothesis, even acting in a 10°C latitudinal range within tropical climates.
Combined analysis of differentially expressed lncRNAs and miRNAs in liver tissues of high-fat fed rabbits by transcriptome sequencing

High-fat diet could lead to a series of metabolic diseases, including obesity, and its mechanism is not clear. In this study, the rabbit individuals were fed with high-fat diet, the liver tissues were collected, high-throughput sequencing technology was used to reveal the expression of lncRNA and miRNA difference, and the molecular regulation mechanism of lncRNA-miRNA. A total of 24,615 DE lncRNAs and 52 DE miRNAs were identified, including 15 novel discovered DE miRNAs (5 upregulated and 10 downregulated). Furthermore, five miRNAs and three mRNAs were verified by qRT-PCR, and the results showed that the expression of the DE miRNAs and DE lncRNAs in the two groups was consistent with our sequencing results. GO and KEGG analyzed 7,57,139 target genes respectively, enriching the pathways related to lipid metabolism, including mucin O-glycan biosynthesis pathway, insulin resistance and glucagon signaling pathway. Moreover, 65 targeting relationships were obtained. Among them, LOC103348122/miR-450a-5p, LOC103350359/miR-450a-3p and LOC103350429/miR-148a-5p were proposed the first time. Significantly, LOC103348122/miR-450a-5p and LOC103350429/miR-148a-5p were related to lipid metabolism in the liver. This study is of great significance to the CeRNA regulatory network related to lipid metabolism in the liver of rabbits, and provides a basis for understanding hepatic steatosis in rabbits.
Exploring the cooling effect of urban parks based on the ECOSTRESS land surface temperature

Understanding the cooling effect (CE) of urban parks is vital to mitigate the urban heat islands. ECOsystem Spaceborne Thermal Radiometer Experiment on Space Station (ECOSTRESS) land surface temperature data (LST) data were used to construct diurnal thermal variations to explore the CE of urban parks in the fifth ring regions of Beijing. Local climate zone (LCZ) classification was used to distinguish different parks for examining the internal CE of parks. New subclasses of LCZ (e.g., LCZAG, LCZBG, LCZCG) were created based on the basic subclasses, such as LCZA (mainly consist of dense trees), LCZB (scattered tress with dense bush), LCZC (scattered bush), and LCZG (water). The external CE of parks was evaluated in different directions, and the impacts of buildings around parks on the external CE were also analyzed. The results showed that urban parks tended to heat up slower than the whole urban regions during the daytime, and water releasing energy dominated the mean LST of parks at night. Large parks meeting the minimum area (40,000 m2) of LCZ had better CE inside each park during the daytime. Three hundred thirty four large parks were divided into six types of LCZ. The strength of the CE decrease with the increases of distance, and seemed to exist at a distance of up to 150–200 m. Such impacts of parks were insignificant at night. In addition, parks containing certain dense trees and water had better CE inside and out. The height and density of buildings had a relatively obvious impact on the CE of parks. This study can provide insight into the impacts of urban parks on the urban thermal environment and promote the CE of urban parks in future urban planning.
Insights on the biochemical and cellular changes induced by heat stress in the Cladocopium isolated from coral Mussismilia braziliensis

Corals are treatened by global warming. Bleaching is one immediate effect of global warming, resulting from the loss of photosynthetic endosymbiont dinoflagellates. Understanding host-symbiont associations are critical for assessing coral’s habitat requirements and its response to environmental changes. Cladocopium (formerly family Symbiodiniaceae clade C) are dominant endosymbionts in the reef-building coral, Mussismilia braziliensis. This study aimed to investigate the effect of temperature on the biochemical and cellular features of Cladocopium. Heat stress increased oxygen (O2) and decreased proteins, pigments (Chla + Chlc2), hexadecanoic acid- methyl ester, methyl stearate, and octadecenoic acid (Z)- methyl ester molecules. In addition, there was an increase in neutral lipids such as esterified cholesterol and a decrease in free fatty acids that may have been incorporated for the production of lipid droplets. Transmission electron microscopy (TEM) demonstrated that Cladocopium cells subjected to heat stress had thinner cell walls, deformation of chloroplasts, and increased lipid droplets after 3 days at 28°C. These findings indicate that thermal stress negatively affects isolated Cladocopium spp. from Mussismilia host coral.
Parental smoking exposure before and during pregnancy and offspring attention-deficit/hyperactivity disorder risk: A Chinese child and adolescent cohort study

Background Previous studies revealed that maternal smoking exposure during pregnancy was an essential risk factor for offspring developing attention-deficit/hyperactivity disorder (ADHD). The impact of paternal smoking exposure 1 year before pregnancy on offspring ADHD risk is still unclear. Methods The present study included 2,477 school-age children and their parents from the Shanghai Child and Adolescent Health Cohort who had complete data for offspring ADHD diagnosis and parents' smoking exposure before and during pregnancy information. A multivariate logistic regression model and Firth's logistic regression model were used to determine the associations of paternal smoking and parental smoke exposure patterns before and during pregnancy with offspring ADHD risk. Results Children whose fathers smoked before pregnancy had a higher risk of developing ADHD [odds ratio (OR) = 2.59, 95% confidence interval (CI): 1.35–4.98] compared to those whose fathers had never been exposed to smoking. Similarly, parents who were exposed to smoking or second-hand smoke before pregnancy had 1.96 times (OR = 1.96, 95% CI: 1.19–3.22) more likely to have offspring with ADHD. Moreover, children whose parents were exposed to smoking both before and during pregnancy were 2.01 times (OR = 2.01, 95% CI: 1.29–3.12) more likely to develop ADHD. Conclusion Paternal smoking before pregnancy and parental smoking exposure 1 year ahead of and throughout pregnancy were all risk factors for offspring developing ADHD.
A twenty-year journey exploring coumarin-based derivatives as bioactive molecules

The coumarin core (i.e., 1-benzopyran-2 (2H)-one) is a structural motif highly recurrent in both natural products and bioactive molecules. Indeed, depending on the substituents and branching positions around the byciclic core, coumarin-containing compounds have shown diverse pharmacological activities, ranging from anticoagulant activities to anti-inflammatory, antimicrobial, anti-HIV and antitumor effects. In this survey, we have reported the main scientific results of the 20-years investigation on the coumarin core, exploited by the research group headed by Prof. Angelo Carotti (Bari, Italy) either as a scaffold or a pharmacophore moiety in designing novel biologically active small molecules.