The inability to guide the nucleation locations of electrochemically deposited Li has long been considered the main factor limiting the utilization of high‐energy‐density Li‐metal batteries. In this ...study, an electrical conductivity gradient interfacial host comprising 1D high conductivity copper nanowires and nanocellulose insulating layers is used in stable Li‐metal anodes. The conductivity gradient system guides the nucleation sites of Li‐metal to be directed during electrochemical plating. Additionally, the controlled parameter of the intermediate layer affects the highly stable Li‐metal plating. The electrochemical behavior is confirmed through experiments associated with the COMSOL Multiphysics simulation data. The distributed Li‐ion reaction flux resulting from the controlled electrical conductivity enables stable cycling for more than 250 cycles at 1 mA cm−2. The gradient system effectively suppresses dendrite growth even at a high current density of 5 mA cm−2 and ensures Li plating and stripping with ultra‐long‐term stability. To demonstrate the high‐energy‐density full‐cell application of the developed anode, it is paired with the LiNi0.8Co0.1Mn0.1O2 cathode. The cells demonstrate a high capacity retention of 90% with an extremely high Coulombic efficiency of 99.8% over 100 cycles. These results shed light on the formidable challenges involved in exploiting the engineering aspects of high‐energy‐density Li‐metal batteries.
An electrical conductivity gradient interfacial host composed of simply fabricated 1D high conductivity copper nanowires and nanocellulose insulating layers shows stable lithium metal plating/stripping during electrochemical reaction. The conductivity gradient offers to guide the nucleation of lithium metal deposition, resulting in a high capacity retention of 90% with an extremely high Coulombic efficiency of 99.8% over 100 cycles as a full‐cell test.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Low-intensity, low-frequency ultrasound (LILFU) is the next-generation, non-invasive brain stimulation technology for treating various neurological and psychiatric disorders. However, the underlying ...cellular and molecular mechanism of LILFU-induced neuromodulation has remained unknown. Here, we report that LILFU-induced neuromodulation is initiated by opening of TRPA1 channels in astrocytes. The Ca2+ entry through TRPA1 causes a release of gliotransmitters including glutamate through Best1 channels in astrocytes. The released glutamate activates NMDA receptors in neighboring neurons to elicit action potential firing. Our results reveal an unprecedented mechanism of LILFU-induced neuromodulation, involving TRPA1 as a unique sensor for LILFU and glutamate-releasing Best1 as a mediator of glia-neuron interaction. These discoveries should prove to be useful for optimization of human brain stimulation and ultrasonogenetic manipulations of TRPA1.
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•Ultrasound-induced neuromodulation is initiated by opening of TRPA1 in astrocytes•The Ca2+ entry through TRPA1 causes a release of glutamate through Best1 channels•The released glutamate activates NMDA receptors in neighboring neurons
Oh et al. show that TRPA1 is the molecular sensor and transducer for low-intensity, low-frequency ultrasound (LILFU). With TRPA1’s unique co-localization and cooperation with the glutamate-releasing Ca2+-activated Best1 at the microdomains of astrocytes, LILFU is capable of eliciting neuromodulation as a consequence of neuronal NMDAR activation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Genome-wide association studies are designed to discover SNPs that are associated with a complex trait. Employing strict significance thresholds when testing individual SNPs avoids false positives at ...the expense of increasing false negatives. Recently, we developed a method for quantitative traits that estimates the variation accounted for when fitting all SNPs simultaneously. Here we develop this method further for case-control studies. We use a linear mixed model for analysis of binary traits and transform the estimates to a liability scale by adjusting both for scale and for ascertainment of the case samples. We show by theory and simulation that the method is unbiased. We apply the method to data from the Wellcome Trust Case Control Consortium and show that a substantial proportion of variation in liability for Crohn disease, bipolar disorder, and type I diabetes is tagged by common SNPs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Genetic variation in response to the environment, that is, genotype-by-environment interaction (GxE), is fundamental in the biology of complex traits and diseases. However, existing methods are ...computationally demanding and infeasible to handle biobank-scale data. Here, we introduce GxEsum, a method for estimating the phenotypic variance explained by genome-wide GxE based on GWAS summary statistics. Through comprehensive simulations and analysis of UK Biobank with 288,837 individuals, we show that GxEsum can handle a large-scale biobank dataset with controlled type I error rates and unbiased GxE estimates, and its computational efficiency can be hundreds of times higher than existing GxE methods.
The accumulation of misfolded and aggregated proteins is a hallmark of neurodegenerative proteinopathies. Although multiple genetic loci have been associated with specific neurodegenerative diseases ...(NDs), molecular mechanisms that may have a broader relevance for most or all proteinopathies remain poorly resolved. In this study, we developed a multi‐layered network expansion (MLnet) model to predict protein modifiers that are common to a group of diseases and, therefore, may have broader pathophysiological relevance for that group. When applied to the four NDs Alzheimer's disease (AD), Huntington's disease, and spinocerebellar ataxia types 1 and 3, we predicted multiple members of the insulin pathway, including PDK1, Akt1, InR, and sgg (GSK‐3β), as common modifiers. We validated these modifiers with the help of four Drosophila ND models. Further evaluation of Akt1 in human cell‐based ND models revealed that activation of Akt1 signaling by the small molecule SC79 increased cell viability in all models. Moreover, treatment of AD model mice with SC79 enhanced their long‐term memory and ameliorated dysregulated anxiety levels, which are commonly affected in AD patients. These findings validate MLnet as a valuable tool to uncover molecular pathways and proteins involved in the pathophysiology of entire disease groups and identify potential therapeutic targets that have relevance across disease boundaries. MLnet can be used for any group of diseases and is available as a web tool at http://ssbio.cau.ac.kr/software/mlnet.
Synopsis
MLnet is a multi‐layered network expansion model that finds proteins with pathophysiological relevance for groups of diseases. Application to four neurodegenerative diseases predicts multiple members of the insulin pathway as common modifiers.
MLnet uses data integration and a multi‐layered network expansion model to identify and prioritize for experimental testing proteins that affect pathophysiology across multiple diseases.
When applied to Alzheimer's disease, Huntington's disease, and spinocerebellar ataxia types 1 and 3, MLnet identifies multiple members of the insulin pathway, proteostasis machinery and microtubule apparatus as common modifiers.
The impact of the identified genes on neurodegenerative disease phenotypes is tested in Drosophila, human cell lines and mouse disease models.
MLnet is available at http://ssbio.cau.ac.kr/software/mlnet and can be used for any group of diseases.
MLnet is a multi‐layered network expansion model that finds proteins with pathophysiological relevance for groups of diseases. Application to four neurodegenerative diseases predicts multiple members of the insulin pathway as common modifiers.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
The development of bioadhesives has become an emerging research field for tissue sealants, wound dressings, and hemostatic agents. However, assembling hydrogels using bioadhesive‐mediated attachment ...remains a challenging task. Significantly high water content (>90%) in hydrogels compared to that of biological tissues is the main cause of failure. Considering that hydrogels are primary testing scaffolds mimicking in vivo environments, developing strategies to assemble hydrogels that exhibit diverse properties is important. Self‐healing gels have been reported, but such gels often lack biocompatibility, and two gel pieces should be identical in chemistry for assembly, thus not allowing co‐existence of diverse biological environments. Herein, a mussel‐mimetic cis‐diol‐based adhesive, alginate‐boronic acid, that exhibits pH‐responsive curing from a viscoelastic solution to soft gels is developed. Associated mechanisms are that 1) polymeric diffusion occurs at interfaces utilizing intrinsic high water content; 2) the conjugated cis‐diols strongly interact/entangle with hydrogel chains; 3) curing processes begin by a slight increase in pH, resulting in robust attachment of diverse types of hydrogel building blocks for assembly. The findings obtained with alginate‐boronic acid glues suggest a rational design principle to attach diverse hydrogel building blocks to provide platforms mimicking in vivo environments.
A versatile hydrogel assembly is presented via a mussel‐mimetic boronic acid gluing mechanism. The boronic acid‐containing glue shows phase transition of a viscoelastic solution to a gel upon post‐curing at physiological pH. The strong adhesion provides long‐lasting stability of the assembled hydrogel blocks in both static and dynamic environments, as well as enhanced tissue‐to‐hydrogel attachment for further biomedical application regarding tissue regenerative engineering.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In multi-class indoor semantic segmentation using RGB-D data, it has been shown that incorporating depth feature into RGB feature is helpful to improve segmentation accuracy. However, previous ...studies have not fully exploited the potentials of multi-modal feature fusion, e.g., simply concatenating RGB and depth features or averaging RGB and depth score maps. To learn the optimal fusion of multimodal features, this paper presents a novel network that extends the core idea of residual learning to RGB-D semantic segmentation. Our network effectively captures multilevel RGB-D CNN features by including multi-modal feature fusion blocks and multi-level feature refinement blocks. Feature fusion blocks learn residual RGB and depth features and their combinations to fully exploit the complementary characteristics of RGB and depth data. Feature refinement blocks learn the combination of fused features from multiple levels to enable high-resolution prediction. Our network can efficiently train discriminative multi-level features from each modality end-to-end by taking full advantage of skip-connections. Our comprehensive experiments demonstrate that the proposed architecture achieves the state-of-the-art accuracy on two challenging RGB-D indoor datasets, NYUDv2 and SUN RGB-D.
Since around the year 2000, hundreds of people in Korea have developed humidifier disinfectant‐associated lung injury (HDLI). We collected all HD exposure‐related information from the field ...investigations into the locations in which the 1199 registered patients had used HD. Among the people who registered, 38% (1st round = 214, 2nd = 73, 3rd = 166) were confirmed as HDLI patients. Children aged under eight years old made up the highest proportion of HDLI cases (N = 279, 62%), followed by pregnant women (N = 31, 7%). One hundred thirty‐three (29%) of the confirmed HDLI patients died. Fifty‐seven percent of HDLI patients (N = 259) developed HDLI after <1 year of HD use. The number of HDLI patients who used only the Oxy Saksak HD brand was found to be 176 (39%), followed by the brands Cefu (N = 27, 6%) and Aekyung (N = 22, 5%). HD products containing only polyhexamethylene guanidine phosphate (PHMG‐P) were the most frequently used among HDLI patients (N = 234, 52%), followed by oligo (2‐(2‐ethoxy)ethoxyethyl) guanidinium (PGH) (N = 27, 6%) and a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) (N = 26, 6%). The average PHMG‐P inhalation level estimated from the patient group classified as suffering lung injury definitely associated with HD use was 145.1 μg/m3 (N = 91, SD = 395.1 μg/m3), higher than levels estimated from both the probable and possible HDLI patient groups. In conclusion, HD exposure‐related variables, including type of HD brand and estimated inhalation HD level, were associated with the risk of HDLI.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
OBJECTIVES:This study aimed to compare the prognostic value of lactate level and lactate clearance at 6 hours after septic shock recognition. And, we performed it to determine lactate kinetics in the ...Sepsis-3 defined septic shock.
DESIGN:This retrospective study was performed from a prospective septic shock registry.
SETTINGS:This study was performed at single urban tertiary center. And, all patients were treated with protocol-driven resuscitation bundle therapy between 2010 and 2016.
PATIENTS:We included septic shock patients who met the Sepsis-3 definition, which involves lactate levels greater than or equal to 2 mmol/L and vasopressor use.
INTERVENTIONS:Serum lactate levels were measured at initial and 6 hours from septic shock recognition.
MEASUREMENTS AND MAIN RESULTS:Lactate clearance was calculated as (initial lactate – 6-hr lactate/initial lactate) × 100. The prognostic value of measured lactate levels and lactate clearance for 28-day mortality was analyzed and compared with that of subsequent lactate levels greater than or equal to 2 mmol/L, greater than or equal to 3 mmol/L, and greater than or equal to 4 mmol/L and less than 10%, less than 20%, and less than 30% lactate clearance. A total of 1,060 septic shock patients by Sepsis-3, 265 patients died (28-d mortality25%). In survivor, groups had lower median 6-hour lactate level and higher lactate clearance than nonsurvivors (2.5 vs 4.6 mmol/L and 35.4% vs 14.8%; p < 0.01). Both lactate and lactate clearance were associated with mortality after adjusting for confounders (odd ratio, 1.27 95% CI, 1.21–1.34 and 0.992 95% CI, 0.989–0.995), but lactate had a significantly higher prognostic value than lactate clearance (area under the curve, 0.70 vs 0.65; p < 0.01). The prognostic value of subsequent lactate levels (≥ 2, ≥ 3, and ≥ 4 mmol/L) and lactate clearances (< 10%, < 20%, and < 30%) was not significantly differed. However, lactate levels of greater than or equal to 2 mmol/L had the greatest sensitivity (85.3%).
CONCLUSIONS:Our findings indicate lactate and lactate clearance are both useful targets in patients with septic shock defined by Sepsis-3. Serum lactate level at 6-hour can be an easier and more effective tool for prognosis of septic shock patients who were treated with protocol-driven resuscitation bundle therapy.
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