Miracle-dz/UniFAR-FTUs huggingface dataset:
Endocannabinoids produced in photoreceptor cells in response to light activate Drosophila TRP channels

Drosophila phototransduction is a model for signaling cascades that culminate in the activation of transient receptor potential (TRP) cation channels. TRP and TRPL are the canonical TRP (TRPC) channels that are regulated by light stimulation of rhodopsin and engagement of Gαq and phospholipase Cβ (PLC). Lipid metabolite(s) generated downstream of PLC are essential for the activation of the TRPC channels in photoreceptor cells. We sought to identify the key lipids produced subsequent to PLC stimulation that contribute to channel activation. Here, using genetics, lipid analysis, and Ca2+ imaging, we found that light increased the amount of an abundant endocannabinoid, 2-linoleoyl glycerol (2-LG), in vivo. The increase in 2-LG amounts depended on the PLC and diacylglycerol lipase encoded by norpA and inaE, respectively. This endocannabinoid facilitated TRPC-dependent Ca2+ influx in a heterologous expression system and in dissociated ommatidia from compound eyes. Moreover, 2-LG and mechanical stimulation cooperatively activated TRPC channels in ommatidia. We propose that 2-LG is a physiologically relevant endocannabinoid that activates TRPC channels in photoreceptor cells. Description Light induces the generation of endocannabinoids in photoreceptor cells that activate Drosophila TRP channels. Endocannabinoids light the way The Drosophila eye is a model system for phototransduction. Light exposure of photoreceptors stimulates a signaling cascade that induces the phospholipase C (PLC) NORPA to generate lipids that stimulate Ca2+ influx through the cation channels TRP and TRPL. Sokabe et al. identified the endocannabinoids produced in response to light that activated TRP and TRPL. In addition to NORPA, light-induced endocannabinoid synthesis required the diacylglycerol lipase INAE. One of the endocannabinoids also activated the related mammalian channels TRPC5 and TRPC6. Because Drosophila lack homologs of mammalian cannabinoid receptors, the authors propose that TRP and TRPL are the endogenous receptors for endocannabinoids in this model organism.
How do manufacturing and producer service agglomerations affect urban innovation differently? Empirical evidence from China

Despite the growing body of literature on the influence of industrial agglomeration on urban innovation, no consensus has been reached on the mechanism of the spillover effect. This empirical study exploits heterogeneity in spillover effects between manufacturing and producer service agglomerations on urban innovation based on a sample of 262 prefecture-level cities in China. We find some intriguing and new findings: (1) The threshold effect can be identified for the spillover effect of manufacturing agglomeration but not for that of producer service agglomeration. (2) Manufacturing and producer service agglomerations have opposite decomposition indirect effect. (3) The spatial spillover effect of industrial agglomeration can be restrained by absorptive capacity of nearby cities. This study not only provides empirical evidence for the reconciliation of the debate on the effect of manufacturing and producer service agglomeration, but also has important policy implication for reconsidering the role of industrial agglomeration in urban innovation.
Optimal Cost-Effective Screening Strategy for Unruptured Intracranial Aneurysms in Female Smokers

BACKGROUND: The prevalence of intracranial aneurysms among female cigarette smokers was shown to be high in previous studies, yet the cost-effectiveness of screening them has never been explored. OBJECTIVE: To explore the most cost-effective screening strategy for female smokers. METHODS: A decision analytical study was performed with a Markov model to compare different screening strategies with no screening and to explore the most optimal screening strategy for female smokers. Input data for the model were extracted from literature. A single screening at different ages and multiple screening every 15 years, 10 years, 5 years, and 2 years were performed for female smokers in different age ranges. Deterministic and probabilistic sensitivity analyses were performed to evaluate the robustness of the model. Finally, value of information analysis was performed to investigate the value of collecting additional data. RESULTS: Screening female smokers for unruptured intracranial aneurysm is cost-effective. All screening strategies yield extra quality-adjusted life years. Screening at younger age brings more health benefit at lower cost. Frequent screening strategies decrease rupture rate of aneurysms more with higher costs per quality-adjusted life year. Screening after age 70 years and frequent screening (every 2 years) after age 60 years is not optimal. Among all the parameters in the model, collecting additional data on utility of the unscreened population would be most valuable. CONCLUSION: Screening female smokers for intracranial aneurysms once at younger age is most optimal. However, in clinical practice, the duration and intensity of exposure to cigarettes should be taken into consideration.
A draft reference genome of the Vernal Pool Fairy Shrimp, Branchinecta lynchi

Abstract We present the reference genome of the Vernal Pool Fairy Shrimp Branchinecta lynchi. This branchiopod crustacean is endemic to California’s freshwater ephemeral ponds. It faces enormous habitat loss and fragmentation as urbanization and agriculture have fundamentally changed the vernal pool landscape over the past 3 centuries. The assembled genome consists of 22 chromosome-length scaffolds that account for 96.85% of the total sequence. One hundred and ninety-five unscaffolded contigs comprise the rest of the genome’s 575.6 Mb length. The genome is substantially complete with a BUSCO score of 90.0%. There is no immediately identifiable sex chromosome, typical for this class of organism. This new resource will permit researchers to better understand the adaptive capacity of this imperiled species, as well as answer lingering questions about anostracan physiology, sex determination, and development.
Aggregate-functions MoM approaches for the analysis of complex bodies

In this communication we review some recent advances in aggregate-functions approaches, that are based on the construction of efficient MoM basis functions by suitably grouping standard (e.g. Rao-Wilton-Glisson, RWG) functions. The application domains, objectives and related means of achieving them can be significantly different for the various embodiments of the aggregate-functions concept. Compressive approaches can reduce the degrees of freedom of the problem up to allowing a direct, iteration-free solution; non-compressive multiscale approaches can act as effective pre-conditioners for iterative methods. For this reason aggregate-functions are well suited to solve antenna, EMC and scattering problems involving large and complex objects.
Appraising two-Dimensional Inequality: A Questionnaire-Experimental Approach

This paper aims to study the extent to which people's intuitions about the distribution of two attributes within a society are consistent with the different axiomatizations proposed by the economists. In particular, the objective is to compare two alternative principles, namely aversion to dispersion of attributes and aversion to correlation between attributes. By using a questionnaire approach, most people are found to be more averse to correlation rather than averse to dispersion.
THE LONG-TERM X-RAY VARIABILITY OF BROAD ABSORPTION LINE QUASARS

We analyze the long-term (rest-frame 3–30 yr) X-ray variability of 11 broad absorption line (BAL) quasars, mainly to constrain the variation properties of the X-ray absorbing shielding gas that is thought to play a critical role in BAL wind launching. Our BAL quasar sample has coverage with multiple X-ray observatories including Chandra, XMM-Newton, BeppoSAX, ASCA, ROSAT, and Einstein; 3–11 observations are available for each source. For seven of the eleven sources we have obtained and analyzed new Chandra observations suitable for searching for any strong X-ray variability. We find highly significant X-ray variability in three sources (PG 1001+054, PG 1004+130, and PG 2112+059). The maximum observed amplitude of the 2–8 keV variability is a factor of 3.8 ± 1.3, 1.5 ± 0.2, and 9.9 ± 2.3 for PG 1001+054, PG 1004+130, and PG 2112+059, respectively, and these sources show detectable variability on rest-frame timescales down to 5.8, 1.4, and 0.5 yr. For PG 1004+130 and PG 2112+059 we also find significant X-ray spectral variability associated with the flux variability. Considering our sample as a whole, we do not find that BAL quasars exhibit exceptional long-term X-ray variability when compared to the quasar population in general. We do not find evidence for common strong changes in the shielding gas owing to physical rearrangement or accretion-disk rotation, although some changes are found; this has implications for modeling observed ultraviolet BAL variability. Finally, we report for the first time an X-ray detection of the highly polarized and well-studied BAL quasar IRAS 14026+4341 in its new Chandra observation.
Impact of salinity origin on microbial communities in saline springs within the Illinois Basin, USA

Abstract Saline springs within the Illinois Basin result from the discharge of deep‐seated evaporated seawater (brine) and likely contain diverse and complex microbial communities that are poorly understood. In this study, seven saline/mineral springs with different geochemical characteristics and salinity origins were investigated using geochemical and molecular microbiological analyses to reveal the composition of microbial communities inhabiting springs and their key controlling factors. The 16S rRNA sequencing results demonstrated that each spring harbours a unique microbial community influenced by its geochemical properties and subsurface conditions. The microbial communities in springs that originated from Cambrian/Ordovician strata, which are deep confined units that have limited recharge from overlying formations, share a greater similarity in community composition and have a higher species richness and more overlapped taxa than those that originated from shallower Pennsylvanian strata, which are subject to extensive regional surface and groundwater recharge. The microbial distribution along the spring flow paths at the surface indicates that 59.8%–94.2% of total sequences in sedimentary samples originated from spring water, highlighting the role of springs in influencing microbiota in the immediate terrestrial environment. The results indicate that the springs introduce microbiota with a high biodiversity into surface terrestrial or aquatic ecosystems, potentially affecting microbial reservoirs in downstream ecosystems.
Early identification of heart failure deterioration through respiratory monitoring with adaptive servo‐ventilation

Cardiac decompensation is associated with worse prognosis in patients with heart failure. Reliable methods to predict cardiac decompensation events are not yet available. Sleep‐disordered breathing (SDB) is a frequent comorbidity in heart failure, and it has been shown to correlate with heart failure severity. This prospective observational trial investigated SDB characteristics in patients with heart failure with the aim to identify patterns that may predict early cardiac decompensation. Patients with heart failure with diagnosed SDB and hospitalised for cardiac decompensation were prospectively enrolled and treated with adaptive servo‐ventilation (ASV). SDB characteristics, daily body weight and clinical cardiac decompensation events were collected over a 1‐year follow‐up. Clinical events were categorised by an independent clinical event committee. A total of 43 patients were enrolled (81% male, mean [SD] age 71 [11] years, body mass index 30 kg/m2, 95% New York Heart Association function class III or IV, mean [SD] left ventricular ejection fraction 37% [11%], median apnea–hypopnoea index [AHI] of 37 events/h). A total of 48 cardiac decompensation events were recorded during the 1‐year study period. Respiratory rate was found to be significantly lower in patients with cardiac decompensation. The AHI and applied inspiratory pressure ASV‐device support were significantly increased 10 days before a clinical cardiac decompensation event. Device usage was also found to be significantly decreased 2 nights before cardiac decompensation. Device‐derived respiratory data in ASV therapy devices for SDB may therefore serve as a monitoring tool to predict early clinical cardiac decompensation events. Prediction and avoidance of cardiac decompensation, in turn, may attenuate serious health consequences in patients with heart failure.
Separating Features From Functionality in Vaccination Apps: Computational Analysis

Background Some latest estimates show that approximately 95% of Americans own a smartphone with numerous functions such as SMS text messaging, the ability to take high-resolution pictures, and mobile software apps. Mobile health apps focusing on vaccination and immunization have proliferated in the digital health information technology market. Mobile health apps have the potential to positively affect vaccination coverage. However, their general functionality, user and disease coverage, and exchange of information have not been comprehensively studied or evaluated computationally. Objective The primary aim of this study is to develop a computational method to explore the descriptive, usability, information exchange, and privacy features of vaccination apps, which can inform vaccination app design. Furthermore, we sought to identify potential limitations and drawbacks in the apps’ design, readability, and information exchange abilities. Methods A comprehensive codebook was developed to conduct a content analysis on vaccination apps’ descriptive, usability, information exchange, and privacy features. The search and selection process for vaccination-related apps was conducted from March to May 2019. We identified a total of 211 apps across both platforms, with iOS and Android representing 62.1% (131/211) and 37.9% (80/211) of the apps, respectively. Of the 211 apps, 119 (56.4%) were included in the final study analysis, with 42 features evaluated according to the developed codebook. The apps selected were a mix of apps used in the United States and internationally. Principal component analysis was used to reduce the dimensionality of the data. Furthermore, cluster analysis was used with unsupervised machine learning to determine patterns within the data to group the apps based on preselected features. Results The results indicated that readability and information exchange were highly correlated features based on principal component analysis. Of the 119 apps, 53 (44.5%) were iOS apps, 55 (46.2%) were for the Android operating system, and 11 (9.2%) could be found on both platforms. Cluster 1 of the k-means analysis contained 22.7% (27/119) of the apps; these were shown to have the highest percentage of features represented among the selected features. Conclusions We conclude that our computational method was able to identify important features of vaccination apps correlating with end user experience and categorize those apps through cluster analysis. Collaborating with clinical health providers and public health officials during design and development can improve the overall functionality of the apps.
KinMod database: a tool for investigating metabolic regulation

Abstract The ability of current kinetic models to simulate the phenotypic behaviour of cells is limited since cell metabolism is regulated at different levels including enzyme regulation. The small molecule regulation network (SMRN) enables cells to respond rapidly to environmental fluctuations by controlling the activity of enzymes in metabolic pathways. However, SMRN is not as well studied relative to metabolic networks. The main contributor to the lack of knowledge on this regulatory system is the sparsity of experimental data and the absence of a standard framework for representing available information. In this paper, we introduce the KinMod database that encompasses more than 2 million data points on the metabolism and metabolic regulation network of 9814 organisms KinMod database employs a hierarchical data structure to: (i) signify relationships between kinetic information obtained through in-vitro experiments and proteins, with an emphasis on SMRN, (ii) provide a thorough insight into available kinetic parameters and missing experimental measurements of this regulatory network and (iii) facilitate machine learning approaches for parameter estimation and accurate kinetic model construction by providing a homogeneous list of linked omics data. The hierarchical ontology of the KinMod database allows flexible exploration of data attributes and investigation of metabolic relationships within- and cross-species. Identifying missing experimental values suggests additional experiments required for kinetic parameter estimation. Linking multi-omics data and providing data on SMRN encourages the development of novel machine learning techniques for predicting missing kinetic parameters and promotes accurate kinetic model construction of cells metabolism by providing a comprehensive list of available kinetic measurements. To illustrate the value of KinMod data, we develop six analyses to visualize associations between data classes belonging to separate sections of the metabolism. Through these analyses, we demonstrate that the KinMod database provides a unique framework for biologists and engineers to retrieve, evaluate and compare the functional metabolism of species, including the regulatory network, and discover the extent of available and missing experimental values of the metabolic regulation. Database URL: https://lmse.utoronto. ca/kinmod/KINMOD.sql. gz
Nonlinear waves in PT -symmetric systems

The concept of parity-time symmetric systems is rooted in non-Hermitian quantum mechanics where complex potentials obeying this symmetry could exhibit real spectra. The concept has applications in many fields of physics, e.g., in optics, metamaterials, acoustics, Bose-Einstein condensation, electronic circuitry, etc. The inclusion of nonlinearity has led to a number of new phenomena for which no counterparts exist in traditional dissipative systems. Several examples of nonlinear parity-time symmetric systems in different physical disciplines are presented and their implications discussed.
Endocannabinoid signaling in microglia

Microglia, the innate immune cells of the central nervous system (CNS), execute their sentinel, housekeeping and defense functions through a panoply of genes, receptors and released cytokines, chemokines and neurotrophic factors. Moreover, microglia functions are closely linked to the constant communication with other cell types, among them neurons. Depending on the signaling pathway and type of stimuli involved, the outcome of microglia operation can be neuroprotective or neurodegenerative. Accordingly, microglia are increasingly becoming considered cellular targets for therapeutic intervention. Among signals controlling microglia activity, the endocannabinoid (EC) system has been shown to exert a neuroprotective role in many neurological diseases. Like neurons, microglia express functional EC receptors and can produce and degrade ECs. Interestingly, boosting EC signaling leads to an anti‐inflammatory and neuroprotective microglia phenotype. Nonetheless, little evidence is available on the microglia‐mediated therapeutic effects of EC compounds. This review focuses on the EC signals acting on the CNS microglia in physiological and pathological conditions, namely on the CB1R, CB2R and TRPV1‐mediated regulation of microglia properties. It also provides new evidence, which strengthens the understanding of mechanisms underlying the control of microglia functions by ECs. Given the broad expression of the EC system in glial and neuronal cells, the resulting picture is the need for in vivo studies in transgenic mouse models to dissect the contribution of EC microglia signaling in the neuroprotective effects of EC‐derived compounds.
The Impact of Functional Form Complexity on Model Overfitting for Nonlinear Mixed-Effects Models

Abstract Nonlinear mixed-effects models (NLMEMs) allow researchers to model curvilinear patterns of growth, but there is ambiguity as to what functional form the data follow. Often, researchers fit multiple nonlinear functions to data and use model selection criteria to decide which functional form fits the data “best. ” Frequently used model selection criteria only account for the number of parameters in a model but overlook the complexity of intrinsically nonlinear functional forms. This can lead to overfitting and hinder the generalizability and reproducibility of results. The primary goal of this study was to evaluate the performance of eight model selection criteria via a Monte Carlo simulation study and assess under what conditions these criteria are sensitive to model overfitting as it relates to functional form complexity. Results highlighted criteria with the potential to capture overfitting for intrinsically nonlinear functional forms for NLMEMs. Information criteria and the stochastic information complexity criterion recovered the true model more often than the average or conditional concordance correlation. Results also suggest that the amount of residual variance and sample size have an impact on model selection for NLMEMs. Implications for future research and recommendations for application are also provided.
A Hamiltonian–Krein (Instability) Index Theory for Solitary Waves to KdV‐Like Eigenvalue Problems

The Hamiltonian–Krein (instability) index is concerned with determining the number of eigenvalues with positive real part for the Hamiltonian eigenvalue problem JLu=λu , where J is skew‐symmetric and L is self‐adjoint. If J has a bounded inverse the index is well established, and it is given by the number of negative eigenvalues of the operator L constrained to act on some finite‐codimensional subspace. There is an important class of problems—namely, those of KdV‐type—for which J does not have a bounded inverse. In this paper, we overcome this difficulty and derive the index for eigenvalue problems of KdV‐type. We use the index to discuss the spectral stability of homoclinic traveling waves for KdV‐like problems and Benjamin—Bona—Mahony‐type problems.