Learning Large-scale Location Embedding From Human Mobility Trajectories with Graphs

An increasing amount of location-based service (LBS) data is being accumulated and helps to study urban dynamics and human mobility. GPS coordinates and other location indicators are normally low dimensional and only representing spatial proximity, thus difficult to be effectively utilized by machine learning models in Geo-aware applications. Existing location embedding methods are mostly tailored for specific problems that are taken place within areas of interest. When it comes to the scale of a city or even a country, existing approaches always suffer from extensive computational cost and significant data sparsity. Different from existing studies, we propose to learn representations through a GCN-aided skip-gram model named GCN-L2V by considering both spatial connection and human mobility. With a flow graph and a spatial graph, it embeds context information into vector representations. GCN-L2V is able to capture relationships among locations and provide a better notion of similarity in a spatial environment. Across quantitative experiments and case studies, we empirically demonstrate that representations learned by GCN-L2V are effective. As far as we know, this is the first study that provides a fine-grained location embedding at the city level using only LBS records. GCN-L2V is a general-purpose embedding model with high flexibility and can be applied in down-streaming Geo-aware applications

The Modification Strategies for Enhancing the Metabolic Stabilities and Pharmacokinetics of Aptamer Drug Candidates

Aptamers are single-stranded DNA or RNA that can mimic the functional properties of monoclonal antibodies. Aptamers have high affinity and specificity for their target molecules, which can make them a promising alternative to therapeutic antibodies or peptide ligands. However, many aptamer drug candidates in clinical development have been discontinued due to suboptimal metabolic stabilities and pharmacokinetics. To address these issues, chemical modification can be used to enhance the metabolic stability and prolong the half-life of aptamer candidates. The chapter reviewed published data regarding the metabolic stability and pharmacokinetics of aptamer drug candidates from preclinical and clinical studies. The benefits and possible shortcomings of current modification strategies used in these aptamers were briefly discussed

Daidzin decreases blood glucose and lipid in streptozotocin-induced diabetic mice

Purpose: To investigate the ameliorative effect of daidzin (DZ) on diabetes in streptozotocin (STZ)- induced diabetic Institute of Cancer Research (ICR) mice, with a view to determining its usefulness in the treatment of diabetes.Methods: The effect of DZ (100, 200 and 400 mg/kg) on blood glucose was investigated in both normal and STZ-induced diabetic mice with glibenclamide (3 mg/kg) and metformin (400 mg/kg) as positive control, respectively. Serum or hepatic levels of lipid, proinflammatory factors, malondialdehyde (MDA) and superoxide dismutase (SOD) were measured. Glucosidase activity assay and glucose uptake by C2C12 myotubes were performed in vitro and the expression of glucose transporter 4 (GLUT4) in C2C12 cells was determined by western blot.Results: DZ (200 and 400 mg/kg) did not decrease fasting blood glucose in normal mice but inhibited starch-induced postprandial glycemia. Oral administration of 400 mg/kg of DZ for 14 days significantly decreased mouse blood glucose (p < 0.01), as well as serum total cholesterol (TC, p < 0.01), triglycerides (TG, p < 0.01), low-density lipoprotein cholesterol (LDL-c, p < 0.01) levels in STZ-induced hyperglycemic mice and improved oral glucose tolerance. The serum and hepatic activity of SOD was enhanced (p < 0.01 and p < 0.001, respectively) while MDA level decreased (p < 0.001). Blood concentrations of interleukin-6 (IL-6, p < 0.001), tumor necrosis factor α (TNF-α, p < 0.01), monocyte chemotactic protein 1 (MCP-1, p < 0.01) were also significantly reduced. In vitro glucosidase activity results showed that DZ inhibited α-glucosidase with IC50 values of 82, 98 and 389 μg/mL for α- glucosidase from S. cerevisiae, Rhizopus sp. and rat intestines, respectively. It also stimulated glucose uptake and GLUT4 membrane translocation in C2C12 myotubes at 20 μM (p < 0.05).Conclusion: Oral administration of DZ is effective in alleviating diabetic hyperglycemia, dyslipidemia and inflammation. Inhibition of α-glucosidase and stimulation of glucose consumption by muscles may account for its inhibitory effect on blood glucose.Keywords: Daidzin, Diabetes, Inflammation, Superoxide dismutase (SOD), Malondialdehyde (MDA), Glucosidase, C2C12 myotubes, Glucose transporte

Evolution of the strange-metal scattering in momentum space of electron-doped La2−xCexCuO4{\rm La}_{2-x}{\rm Ce}_x{\rm CuO}_4

The linear-in-temperature resistivity is one of the important mysteries in the strange metal state of high-temperature cuprate superconductors. To uncover this anomalous property, the energy-momentum-dependent imaginary part of the self-energy Im ${\rm \Sigma}(k, \omega)$ holds the key information. Here we perform systematic doping, momentum, and temperature-dependent angle-resolved photoemission spectroscopy measurements of electron-doped cuprate ${\rm La}_{2-x}{\rm Ce}_x{\rm CuO}_4$ and extract the evolution of the strange metal scattering in momentum space. At low doping levels and low temperatures, Im ${\rm\Sigma} \propto \omega$ dependence dominates the whole momentum space. For high doping levels and high temperatures, Im ${\rm\Sigma} \propto \omega^2$ shows up, starting from the antinodal region. By comparing with the hole-doped cuprates ${\rm La}_{2-x}{\rm Sr}_x{\rm CuO}_4$ and ${\rm Bi}_2{\rm Sr}_2{\rm CaCu}_2{\rm O}_8$, we find a dichotomy of the scattering rate exists along the nodal and antinodal direction, which is ubiquitous in the cuprate family. Our work provides new insight into the strange metal state in cuprates

Application of the Pipeline Embolization Device for Giant Vertebrobasilar Dissecting Aneurysms in Pediatric Patients

Objective: To evaluate the feasibility and effectiveness of the pipeline embolization device (PED) for the treatment of pediatric giant vertebrobasilar dissecting aneurysms (VBDAs).Methods: We retrospectively reviewed our institutional clinical database and identified 2,706 patients who presented with a diagnosis of intracranial aneurysms from January 2016 to June 2018. Among this group, 153 patients were diagnosed with VBDAs, and 54 of these patients underwent PED therapy. The PED technique was used in four patients who were 18 years old or younger at the time of presentation (two males, two females; mean age 9.25 years; age range 8–11 years).Results: All four included pediatric patients were managed with the PED. One patient (25%) was treated with the PED alone, while three (75%) were treated with the PED and coils. One patient died from brainstem infarction or compression of the brainstem, while follow-up of the other three patients revealed favorable outcomes. The mass effect was reduced in cases 1, 2, and 3 on follow-up MRI performed 6 months after the PED procedure.Conclusions: PEDs could be feasible in the treatment of pediatric giant VBDAs. However, the safety and efficacy of this method have not been clarified in this special pediatric population, and long-term follow-up is still necessary

Evidence for acquisition of virulence effectors in pathogenic chytrids

Background The decline in amphibian populations across the world is frequently linked to the infection of the chytrid fungus Batrachochytrium dendrobatidis (Bd). This is particularly perplexing because Bd was only recently discovered in 1999 and no chytrid fungus had previously been identified as a vertebrate pathogen. Results In this study, we show that two large families of known virulence effector genes, crinkler (CRN) proteins and serine peptidases, were acquired by Bd from oomycete pathogens and bacteria, respectively. These two families have been duplicated after their acquisition by Bd. Additional selection analyses indicate that both families evolved under strong positive selection, suggesting that they are involved in the adaptation of Bd to its hosts. Conclusions We propose that the acquisition of virulence effectors, in combination with habitat disruption and climate change, may have driven the Bd epidemics and the decline in amphibian populations. This finding provides a starting point for biochemical investigations of chytridiomycosis

Intronic splicing enhancers, cognate splicing factors and context-dependent regulation rules

SummaryMost human genes produce multiple splicing isoforms with distinct functions. To systematically understand splicing regulation, we conducted an unbiased screen and identified >100 intronic splicing enhancers (ISEs) that were clustered by sequence similarity into six groups. All ISEs functioned in another cell type and heterologous introns, and their distribution and conservation patterns in different pre-mRNA regions are similar to exonic splicing silencers. Consistently all ISEs inhibited use of splice sites from exonic locations. The putative trans-factors of each ISE group were identified and validated. Five distinct ISE motifs were recognized by hnRNP H and F whose C-terminal domains were sufficient to render context-dependent activities of ISEs. The sixth group was controlled by factors that either activate or suppress splicing. This work provided a comprehensive picture of general ISE activities and provided new models of how a single element can function oppositely depending on its locations and binding factors

Study on the Solidification Effect of Dredger Fill by Microbial-Induced Calcium Precipitation (MICP)

This paper puts forward a new soft soil reinforcement technology—microbial-induced calcite precipitation (MICP) technology—which considers the problem of dredger fill soft-soil reinforcement in Dalian Taiping Bay. In this paper, the calcium carbonate content (CCC) and unconfined compressive strength (UCS) of microbial solidified dredger fill (MSDF) samples were determined using laboratory experiments. The microstructure and chemical composition of MSDF samples were studied by SEM–EDS and XRD. The failure and reinforcement mechanism of MSDF under different experimental conditions (ambient temperature, cementation solution concentration, and clay content) were investigated. The results showed that there was a certain residual strength after the peak strength of MSDF. With the increase of ambient temperature, the number of microorganisms increased, but the activities of urease, CCC, and UCS decreased. The UCS and CCC increased with the increase of cementation solution concentration, while they first increased and then decreased with the increase of clay content. The clay content enhanced the compactness of MSDF samples but reduced the soil permeability and weakened the mineralization. There were significant differences in the morphology of microbial-induced precipitation caused by different concentrations of cementation solution

Molecular Imaging in Traditional Chinese Medicine Therapy for Neurological Diseases

With the speeding tendency of aging society, human neurological disorders have posed an ever increasing threat to public health care. Human neurological diseases include ischemic brain injury, Alzheimer’s disease, Parkinson’s disease, and spinal cord injury, which are induced by impairment or specific degeneration of different types of neurons in central nervous system. Currently, there are no more effective treatments against these diseases. Traditional Chinese medicine (TCM) is focused on, which can provide new strategies for the therapy in neurological disorders. TCM, including Chinese herb medicine, acupuncture, and other nonmedication therapies, has its unique therapies in treating neurological diseases. In order to improve the treatment of these disorders by optimizing strategies using TCM and evaluate the therapeutic effects, we have summarized molecular imaging, a new promising technology, to assess noninvasively disease specific in cellular and molecular levels of living models in vivo, that was applied in TCM therapy for neurological diseases. In this review, we mainly focus on applying diverse molecular imaging methodologies in different TCM therapies and monitoring neurological disease, and unveiling the mysteries of TCM