Understanding Usage Patterns for Mobile Phone Excessive Dependence

The advancement of mobile technology has transformed a phone from a simple communication tool to a powerful device for entertainment, socialization and work. The proliferation of mobile apps further changed people’s way of living and working. However, more and more users experience excessive mobile phone dependence. The traditional method to identify dependence uses survey instruments and interview. However, this approach is labour intensive and hard to scale. To address the issue, this research-in-progress paper aims to identity users’ phone usage pattern and propose an unobtrusive way of diagnosing users’ mobile phone dependence. We have developed an app to track users’ phone usage and preliminary analysis was performed based on the data collected over more than 20 days. Users showed different usage patterns over weekends and weekdays, and social app usage is a more significant indicator for mobile phone excessive dependence than general phone usage. Planned future analysis and potential contributions are discussed

Protein structure generation via folding diffusion

The ability to computationally generate novel yet physically foldable protein structures could lead to new biological discoveries and new treatments targeting yet incurable diseases. Despite recent advances in protein structure prediction, directly generating diverse, novel protein structures from neural networks remains difficult. In this work, we present a new diffusion-based generative model that designs protein backbone structures via a procedure that mirrors the native folding process. We describe protein backbone structure as a series of consecutive angles capturing the relative orientation of the constituent amino acid residues, and generate new structures by denoising from a random, unfolded state towards a stable folded structure. Not only does this mirror how proteins biologically twist into energetically favorable conformations, the inherent shift and rotational invariance of this representation crucially alleviates the need for complex equivariant networks. We train a denoising diffusion probabilistic model with a simple transformer backbone and demonstrate that our resulting model unconditionally generates highly realistic protein structures with complexity and structural patterns akin to those of naturally-occurring proteins. As a useful resource, we release the first open-source codebase and trained models for protein structure diffusion

The Dopamine Transporter Recycles via a Retromer-Dependent Postendocytic Mechanism: Tracking Studies Using a Novel Fluorophore-Coupling Approach

Presynaptic reuptake, mediated by the dopamine (DA) transporter (DAT), terminates DAergic neurotransmission and constrains extracellular DA levels. Addictive and therapeutic psychostimulants inhibit DA reuptake and multiple DAT coding variants have been reported in patients with neuropsychiatric disorders. These findings underscore that DAT is critical for DA neurotransmission and homeostasis. DAT surface availability is regulated acutely by endocytic trafficking, and considerable effort has been directed toward understanding mechanisms that govern DAT\u27s plasma membrane expression and postendocytic fate. Multiple studies have demonstrated DAT endocytic recycling and enhanced surface delivery in response to various stimuli. Paradoxically, imaging studies have not detected DAT targeting to classic recycling endosomes, suggesting that internalized DAT targets to either degradation or an undefined recycling compartment. Here, we leveraged PRIME (PRobe Incorporation Mediated by Enzyme) labeling to couple surface DAT directly to fluorophore, and tracked DAT\u27s postendocytic itinerary in immortalized mesencephalic cells. Following internalization, DAT robustly targeted to retromer-positive endosomes, and DAT/retromer colocalization was observed in male mouse dopaminergic somatodendritic and terminal regions. Short hairpin RNA-mediated Vps35 knockdown revealed that DAT endocytic recycling requires intact retromer. DAT also targeted rab7-positive endosomes with slow, linear kinetics that were unaffected by either accelerating DAT internalization or binding a high-affinity cocaine analog. However, cocaine increased DAT exit from retromer-positive endosomes significantly. Finally, we found that the DAT carboxy-terminal PDZ-binding motif was required for DAT recycling and exit from retromer. These results define the DAT recycling mechanism and provide a unifying explanation for previous, seemingly disparate, DAT endocytic trafficking findings. SIGNIFICANCE STATEMENT The neuronal dopamine (DA) transporter (DAT) recaptures released DA and modulates DAergic neurotransmission, and a number of DAT coding variants have been reported in several DA-related disorders, including infantile parkinsonism, attention-deficit/hyperactivity disorder and autism spectrum disorder. DAT is also competitively inhibited by psychostimulants with high abuse potential. Therefore, mechanisms that acutely affect DAT availability will likely exert significant impact on both normal and pathological DAergic homeostasis. Here, we explore the cellular mechanisms that acutely control DAT surface expression. Our results reveal the intracellular mechanisms that mediate DAT endocytic recycling following constitutive and regulated internalization. In addition to shedding light on this critical process, these findings resolve conflict among multiple, seemingly disparate, previous reports on DAT\u27s postendocytic fate

Elevated temperature and browning increase dietary methylmercury, but decrease essential fatty acids at the base of lake food webs

Climate change scenarios predict increases in temperature and organic matter supply from land to water, which affect trophic transfer of nutrients and contaminants in aquatic food webs. How essential nutrients, such as polyunsaturated fatty acids (PUFA), and potentially toxic contaminants, such as methylmercury (MeHg), at the base of aquatic food webs will be affected under climate change scenarios, remains unclear. The objective of this outdoor mesocosm study was to examine how increased water temperature and terrestrially-derived dissolved organic matter supply (tDOM; i.e., lake browning), and the interaction of both, will influence MeHg and PUFA in organisms at the base of food webs (i.e. seston; the most edible plankton size for zooplankton) in subalpine lake ecosystems. The interaction of higher temperature and tDOM increased the burden of MeHg in seston (< 40 mu m) and larger sized plankton (microplankton; 40-200 mu m), while the MeHg content per unit biomass remained stable. However, PUFA decreased in seston, but increased in microplankton, consisting mainly of filamentous algae, which are less readily bioavailable to zooplankton. We revealed elevated dietary exposure to MeHg, yet decreased supply of dietary PUFA to aquatic consumers with increasing temperature and tDOM supply. This experimental study provides evidence that the overall food quality at the base of aquatic food webs deteriorates during ongoing climate change scenarios by increasing the supply of toxic MeHg and lowering the dietary access to essential nutrients of consumers at higher trophic levels

Elevated temperature and browning increase dietary methylmercury, but decrease essential fatty acids at the base of lake food webs

Climate change scenarios predict increases in temperature and organic matter supply from land to water, which affect trophic transfer of nutrients and contaminants in aquatic food webs. How essential nutrients, such as polyunsaturated fatty acids (PUFA), and potentially toxic contaminants, such as methylmercury (MeHg), at the base of aquatic food webs will be affected under climate change scenarios, remains unclear. The objective of this outdoor mesocosm study was to examine how increased water temperature and terrestrially-derived dissolved organic matter supply (tDOM; i.e., lake browning), and the interaction of both, will influence MeHg and PUFA in organisms at the base of food webs (i.e. seston; the most edible plankton size for zooplankton) in subalpine lake ecosystems. The interaction of higher temperature and tDOM increased the burden of MeHg in seston (\u3c 40 μm) and larger sized plankton (microplankton; 40–200 μm), while the MeHg content per unit biomass remained stable. However, PUFA decreased in seston, but increased in microplankton, consisting mainly of filamentous algae, which are less readily bioavailable to zooplankton. We revealed elevated dietary exposure to MeHg, yet decreased supply of dietary PUFA to aquatic consumers with increasing temperature and tDOM supply. This experimental study provides evidence that the overall food quality at the base of aquatic food webs deteriorates during ongoing climate change scenarios by increasing the supply of toxic MeHg and lowering the dietary access to essential nutrients of consumers at higher trophic levels

A Review of Target Mass Corrections

With recent advances in the precision of inclusive lepton--nuclear scattering experiments, it has become apparent that comparable improvements are needed in the accuracy of the theoretical analysis tools. In particular, when extracting parton distribution functions in the large-x region, it is crucial to correct the data for effects associated with the nonzero mass of the target. We present here a comprehensive review of these target mass corrections (TMC) to structure functions data, summarizing the relevant formulas for TMCs in electromagnetic and weak processes. We include a full analysis of both hadronic and partonic masses, and trace how these effects appear in the operator product expansion and the factorized parton model formalism, as well as their limitations when applied to data in the x->1 limit. We evaluate the numerical effects of TMCs on various structure functions, and compare fits to data with and without these corrections.Comment: 41 pages, 13 figures; minor updates to match published versio

Career pathways and professional skills of postgraduate students from a dental research-intensive programme

With current global trends in postgraduate education, graduate programmes must make evidence-based improvements to offer the best programme that aligns with student needs and prepare them for their future career prospects. The aim of this cross-sectional study was to investigate the postgraduation career pathways of MSc and PhD students who graduated within the past 15 years from the McGill University Postgraduate Dental Research Program.An online questionnaire, composed of 10 closed-ended format items, was used that covered domains such as student profile, career profile, postgraduate skill development, job search experience and satisfaction. Descriptive statistics and interpretative qualitative analysis were used to evaluate student feedback.Sixty-six students responded to the online survey, out of which sixty-two students completed the survey (61% participation rate). The majority of the graduate students, 67% (n = 44), obtained MSc degree in Dental Sciences. Overall, our results showed that most graduates started careers in academia in their original field of study and were satisfied with their income. Most graduates reported "critical and creative thinking" to be the strongest acquired skills during their postgraduate training and identified fierce competition for their position of interest as the main challenge after graduation.Our results showed that graduates in dental research appeared to be overall satisfied with their careers after postgraduate research training, both in terms of scope of practice and income. However, strong competition in obtaining the position of their interest seemed to be the main obstacle after graduation.</div

Transcript-indexed ATAC-seq for precision immune profiling.

T cells create vast amounts of diversity in the genes that encode their T cell receptors (TCRs), which enables individual clones to recognize specific peptide-major histocompatibility complex (MHC) ligands. Here we combined sequencing of the TCR-encoding genes with assay for transposase-accessible chromatin with sequencing (ATAC-seq) analysis at the single-cell level to provide information on the TCR specificity and epigenomic state of individual T cells. By using this approach, termed transcript-indexed ATAC-seq (T-ATAC-seq), we identified epigenomic signatures in immortalized leukemic T cells, primary human T cells from healthy volunteers and primary leukemic T cells from patient samples. In peripheral blood CD4+ T cells from healthy individuals, we identified cis and trans regulators of naive and memory T cell states and found substantial heterogeneity in surface-marker-defined T cell populations. In patients with a leukemic form of&nbsp;cutaneous T cell lymphoma, T-ATAC-seq enabled identification of leukemic and nonleukemic regulatory pathways in T cells from the same individual by allowing separation of the signals that arose from the malignant clone from the background T cell noise. Thus, T-ATAC-seq is a new tool that enables analysis of epigenomic landscapes in clonal T cells and should be valuable for studies of T cell malignancy, immunity and immunotherapy

Functional significance may underlie the taxonomic utility of single amino acid substitutions in conserved proteins

We hypothesized that some amino acid substitutions in conserved proteins that are strongly fixed by critical functional roles would show lineage-specific distributions. As an example of an archetypal conserved eukaryotic protein we considered the active site of ß-tubulin. Our analysis identified one amino acid substitution—ß-tubulin F224—which was highly lineage specific. Investigation of ß-tubulin for other phylogenetically restricted amino acids identified several with apparent specificity for well-defined phylogenetic groups. Intriguingly, none showed specificity for “supergroups” other than the unikonts. To understand why, we analysed the ß-tubulin Neighbor-Net and demonstrated a fundamental division between core ß-tubulins (plant-like) and divergent ß-tubulins (animal and fungal). F224 was almost completely restricted to the core ß-tubulins, while divergent ß-tubulins possessed Y224. Thus, our specific example offers insight into the restrictions associated with the co-evolution of ß-tubulin during the radiation of eukaryotes, underlining a fundamental dichotomy between F-type, core ß-tubulins and Y-type, divergent ß-tubulins. More broadly our study provides proof of principle for the taxonomic utility of critical amino acids in the active sites of conserved proteins