Polymyxin-induced neuromuscular weakness: a case report

Polymyxin-induced neuromuscular blockade is a rare but potentially fatal condition, with majority of cases that were reported between 1962 and 1973. We describe a patient who developed hypercapnic respiratory failure after initiation of polymyxin for multi-drug resistant Escherichia Coli bacteremia, due to polymyxin-induced neuromuscular dysfunction. After cessation of polymyxin, he regained full strength, had complete resolution of ptosis, and was successfully extubated. In light of the renewed use of polymyxin in this era of antimicrobial-resistance, this case aims to raise awareness about this rare but life-threatening condition, which is easily reversible with early recognition and prompt discontinuation of the drug

Quantifying Inactive Lithium in Lithium Metal Batteries

Inactive lithium (Li) formation is the immediate cause of capacity loss and catastrophic failure of Li metal batteries. However, the chemical component and the atomic level structure of inactive Li have rarely been studied due to the lack of effective diagnosis tools to accurately differentiate and quantify Li+ in solid electrolyte interphase (SEI) components and the electrically isolated unreacted metallic Li0, which together comprise the inactive Li. Here, by introducing a new analytical method, Titration Gas Chromatography (TGC), we can accurately quantify the contribution from metallic Li0 to the total amount of inactive Li. We uncover that the Li0, rather than the electrochemically formed SEI, dominates the inactive Li and capacity loss. Using cryogenic electron microscopies to further study the microstructure and nanostructure of inactive Li, we find that the Li0 is surrounded by insulating SEI, losing the electronic conductive pathway to the bulk electrode. Coupling the measurements of the Li0 global content to observations of its local atomic structure, we reveal the formation mechanism of inactive Li in different types of electrolytes, and identify the true underlying cause of low Coulombic efficiency in Li metal deposition and stripping. We ultimately propose strategies to enable the highly efficient Li deposition and stripping to enable Li metal anode for next generation high energy batteries

On the Bounds of Function Approximations

Within machine learning, the subfield of Neural Architecture Search (NAS) has recently garnered research attention due to its ability to improve upon human-designed models. However, the computational requirements for finding an exact solution to this problem are often intractable, and the design of the search space still requires manual intervention. In this paper we attempt to establish a formalized framework from which we can better understand the computational bounds of NAS in relation to its search space. For this, we first reformulate the function approximation problem in terms of sequences of functions, and we call it the Function Approximation (FA) problem; then we show that it is computationally infeasible to devise a procedure that solves FA for all functions to zero error, regardless of the search space. We show also that such error will be minimal if a specific class of functions is present in the search space. Subsequently, we show that machine learning as a mathematical problem is a solution strategy for FA, albeit not an effective one, and further describe a stronger version of this approach: the Approximate Architectural Search Problem (a-ASP), which is the mathematical equivalent of NAS. We leverage the framework from this paper and results from the literature to describe the conditions under which a-ASP can potentially solve FA as well as an exhaustive search, but in polynomial time.Comment: Accepted as a full paper at ICANN 2019. The final, authenticated publication will be available at https://doi.org/10.1007/978-3-030-30487-4_3

Forebrain NR2B Overexpression Facilitating the Prefrontal Cortex Long-Term Potentiation and Enhancing Working Memory Function in Mice

Prefrontal cortex plays an important role in working memory, attention regulation and behavioral inhibition. Its functions are associated with NMDA receptors. However, there is little information regarding the roles of NMDA receptor NR2B subunit in prefrontal cortical synaptic plasticity and prefrontal cortex-related working memory. Whether the up-regulation of NR2B subunit influences prefrontal cortical synaptic plasticity and working memory is not yet clear. In the present study, we measured prefrontal cortical synaptic plasticity and working memory function in NR2B overexpressing transgenic mice. In vitro electrophysiological data showed that overexpression of NR2B specifically in the forebrain region resulted in enhancement of prefrontal cortical long-term potentiation (LTP) but did not alter long-term depression (LTD). The enhanced LTP was completely abolished by a NR2B subunit selective antagonist, Ro25-6981, indicating that overexpression of NR2B subunit is responsible for enhanced LTP. In addition, NR2B transgenic mice exhibited better performance in a set of working memory paradigms including delay no-match-to-place T-maze, working memory version of water maze and odor span task. Our study provides evidence that NR2B subunit of NMDA receptor in prefrontal cortex is critical for prefrontal cortex LTP and prefrontal cortex-related working memory

A comprehensive analysis of coherent rainfall patterns in China and potential drivers. Part II: intraseasonal variability

The causes of subseasonal precipitation variability in China are investigated using observations and reanalysis data for extended winter (November–April) and summer (May–October) seasons from 1982 to 2007. For each season, the three dominant regions of coherent intraseasonal variability are identified with Empirical Orthogonal Teleconnection (EOT) analysis. While previous studies have focused on particular causes for precipitation variability or on specific regions, here a comprehensive analysis is carried out with an objective method. Furthermore, the associated rainfall anomaly timeseries are tied to specific locations in China, which facilitates their interpretation. To understand the underlying processes associated with spatially coherent patterns of rainfall variability, fields from observations and reanalysis are regressed onto EOT timeseries. The three dominant patterns in winter together explain 43% of the total space–time variance and have their origins in midlatitude disturbances that appear two pentads in advance. Winter precipitation variability along the Yangtze River is associated with wave trains originating over the Atlantic and northern Europe, while precipitation variability in southeast China is connected to the Mediterranean storm track. In summer, all patterns have a strong relationship with the Boreal Summer Intraseasonal Oscillation and are modulated by the seasonal cycle of the East Asian summer monsoon. The wet and dry phases of the regional patterns can substantially modulate the frequency of daily rainfall across China. The discovered links between weather patterns, precursors, and effects on local and remote precipitation may provide a valuable basis for hydrological risk assessments and the evaluation of numerical weather prediction models

SNX3 controls Wingless/Wnt secretion through regulating retromer-dependent recycling of Wntless

Drosophila Wingless (Wg) acts as a morphogen during development. Wg secretion is controlled by a seven-pass transmembrane cargo Wntless (Wls). We have recently identified retromer as a key regulator involved in Wls trafficking. As sorting nexin (SNX) molecules are essential components of the retromer complex, we hypothesized that specific SNX(s) is required for retromer-mediated Wnt secretion. Here, we generated Drosophila mutants for all of the eight snx members, and identified Drosophila SNX3 (DSNX3) as an essential molecule required for Wg secretion. We show that Wg secretion and its signaling activity are defective in Dsnx3 mutant clones in wing discs. Wg levels in the culture medium of Dsnx3-depleted S2 cells are also markedly reduced. Importantly, Wls levels are strikingly reduced in Dsnx3 mutant cells, and overexpression of Wls can rescue the Wg secretion defect observed in Dsnx3 mutant cells. Moreover, DSNX3 can interact with the retromer component Vps35, and co-localize with Vps35 in early endosomes. These data indicate that DSNX3 regulates Wg secretion via retromer-dependent Wls recycling. In contrast, we found that Wg secretion is not defective in cells mutant for Drosophila snx1 and snx6, two components of the classical retromer complex. Ectopic expression of DSNX1 or DSNX6 fails to rescue the Wg secretion defect in Dsnx3 mutant wing discs and in Dsnx3 dsRNA-treated S2 cells. These data demonstrate the specificity of the DSNX3-retromer complex in Wls recycling. Together, our findings suggest that DSNX3 acts as a cargo-specific component of retromer, which is required for endocytic recycling of Wls and Wg/Wnt secretion

A new integrated and homogenized global monthly land surface air temperature dataset for the period since 1900

A new dataset of integrated and homogenized monthly surface air temperature over global land for the period since 1900 [China Meteorological Administration global Land Surface Air Temperature (CMA-LSAT)] is developed. In total, 14 sources have been collected and integrated into the newly developed dataset, including three global (CRUTEM4, GHCN, and BEST), three regional and eight national sources. Duplicate stations are identified, and those with the higher priority are chosen or spliced. Then, a consistency test and a climate outlier test are conducted to ensure that each station series is quality controlled. Next, two steps are adopted to assure the homogeneity of the station series: (1) homogenized station series in existing national datasets (by National Meteorological Services) are directly integrated into the dataset without any changes (50% of all stations), and (2) the inhomogeneities are detected and adjusted for in the remaining data series using a penalized maximal t test (50% of all stations). Based on the dataset, we re-assess the temperature changes in global and regional areas compared with GHCN-V3 and CRUTEM4, as well as the temperature changes during the three periods of 1900–2014, 1979–2014 and 1998–2014. The best estimates of warming trends and there 95% confidence ranges for 1900–2014 are approximately 0.102 ± 0.006 °C/decade for the whole year, and 0.104 ± 0.009, 0.112 ± 0.007, 0.090 ± 0.006, and 0.092 ± 0.007 °C/decade for the DJF (December, January, February), MAM, JJA, and SON seasons, respectively. MAM saw the most significant warming trend in both 1900–2014 and 1979–2014. For an even shorter and more recent period (1998–2014), MAM, JJA and SON show similar warming trends, while DJF shows opposite trends. The results show that the ability of CMA-LAST for describing the global temperature changes is similar with other existing products, while there are some differences when describing regional temperature changes

Astroglial-Kir4.1 in Lateral Habenula Drives Neuronal Bursts to Mediate Depression

International audienceEnhanced bursting activity of neurons in the lateral habenula (LHb) is essential in driving depression-like behaviours, but the cause of this increase has been unknown. Here, using a high-throughput quantitative proteomic screen, we show that an astroglial potassium channel (Kir4.1) is upregulated in the LHb in rat models of depression. Kir4.1 in the LHb shows a distinct pattern of expression on astrocytic membrane processes that wrap tightly around the neuronal soma. Electrophysiology and modelling data show that the level of Kir4.1 on astrocytes tightly regulates the degree of membrane hyperpolarization and the amount of bursting activity of LHb neurons. Astrocyte-specific gain and loss of Kir4.1 in the LHb bidirectionally regulates neuronal bursting and depression-like symptoms. Together, these results show that a glia–neuron interaction at the perisomatic space of LHb is involved in setting the neuronal firing mode in models of a major psychiatric disease. Kir4.1 in the LHb might have potential as a target for treating clinical depression