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Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a congenital heart defect rarely diagnosed beyond infancy. We present a 9-year-old girl who had once been diagnosed as congenital coronary artery fistula. Echogenic mitral chordae tendineae, multiple coronary collaterals within the ventricular septum and free ventricular wall, and a shunting flow from the left coronary artery into the pulmonary artery were prominent echocardiographic features of ALCAPA. Reimplantation of the left coronary artery directly onto the aorta achieved a favorable outcome with regression of left ventricular size and alleviation of mitral regurgitation.

SUMOylation is a post-translational modification exerted various effects on the target proteins. SUMOylation is a highly dynamic and reversible process, which has been shown to play an important role in tumorigenesis. However, the roles of sentrin/SUMO-specific proteases (SENPs), which mediate the reverse process of SUMOylation, in tumorigenesis remains largely unexplored. Here, we uncover a critical role of SENP6 in promoting gastric cancer cells growth via regulating the deSUMOylation of a transcription factor forkhead box protein M1 (FoxM1). We demonstrated that the mRNA and protein levels were elevated in gastric cancer tissues. Overexpression of SENP6 promoted, while RNA interference depletion of endogenous SENP6 inhibited gastric cancer cells growth and the ability of colony formation. By using biochemical assays, we identified FoxM1 as a novel substrate of SENP6 in gastric cancer cells. Thus, our data suggest that SENP6, which is highly expressed in gastric cancer cells, regulates the transcriptional activity and stability of FoxM1 through deSUMOylation.

Venom peptides from predatory organisms are a resource for investigating evolutionary processes such as adaptive radiation or diversification, and exemplify promising targets for biomedical drug development. Terebridae are an understudied lineage of conoidean snails, which also includes cone snails and turrids. Characterization of cone snail venom peptides, conotoxins, has revealed a cocktail of bioactive compounds used to investigate physiological cellular function, predator-prey interactions, and to develop novel therapeutics. However, venom diversity of other conoidean snails remains poorly understood. The present research applies a venomics approach to characterize novel terebrid venom peptides, teretoxins, from the venom gland transcriptomes of Triplostephanus anilis and Terebra subulata. Next-generation sequencing and de novo assembly identified 139 putative teretoxins that were analyzed for the presence of canonical peptide features as identified in conotoxins. To meet the challenges of de novo assembly, multiple approaches for cross validation of findings were performed to achieve reliable assemblies of venom duct transcriptomes and to obtain a robust portrait of Terebridae venom. Phylogenetic methodology was used to identify 14 teretoxin gene superfamilies for the first time, 13 of which are unique to the Terebridae. Additionally, basic local algorithm search tool homology-based searches to venom-related genes and posttranslational modification enzymes identified a convergence of certain venom proteins, such as actinoporin, commonly found in venoms. This research provides novel insights into venom evolution and recruitment in Conoidean predatory marine snails and identifies a plethora of terebrid venom peptides that can be used to investigate fundamental questions pertaining to gene evolution.

In order to study the burial depth of submarine power cables in the German North Sea, the penetration process of ships' anchors in seabed soil was simulated by using the coupled Eulerian–Lagrangian method in Abaqus/Explicit. In the 3D finite element model the sandy seabed was simulated with different densities under both drained and undrained conditions. The resulting penetration mechanism of a ship anchor in sand was verified by field test data. It showed that under specific conditions the penetration depth of a ship's anchor could be more than 1.5 m, which is suggested in “Bundesfachplan Offshore fur die deutsche ausschliesliche Wirtschaftszone der Nordsee 2012 und Umweltbericht” [8] as the standard burial depth of submarine power cables in the German North Sea by Bundesamt fur Seeschifffahrt und Hydrographie (BSH). Numerische Simulation des Penetrationsprozesses eines Schiffsankers in Sand. Um die Verlegetiefe von Offshore-Seekabeln in der Nordsee zu untersuchen, wurde der Penetrationsprozess eines Schiffsankers in den Meeresboden mittels der gekoppelten Euler-Lagrangeschen Methode im Abaqus/Explicit modelliert. Im 3D-FE-Modell wird der sandige Meeresboden mit unterschiedlichen Lagerungsdichten unter dranierten sowie undranierten Bedingungen angesetzt. Der berechnete Eindringmechanismus des Schiffsankers im Sand wird durch Feldmessungen in der Nordsee bestatigt. Es zeigt sich, dass die Penetrationstiefe des Ankers unter Umstanden groser ist als die im “Bundesfachplan Offshore fur die deutsche ausschliesliche Wirtschaftszone der Nordsee 2012 und Umweltbericht” [8] vom Bundesamt fur Seeschifffahrt und Hydrographie (BSH) vorgegebene Verlegetiefe von 1,5 m.

Learning algorithms have been proposed as a non-selective mechanism capable of creating complex adaptive systems in life. Evolutionary learning however has not been demonstrated to be a plausible cause for the origin of a specific molecular system. Here we show that genetic codes as optimal as the Standard Genetic Code (SGC) emerge readily by following a molecular analog of the Hebb’s rule (“neurons fire together, wire together”). Specifically, error-minimizing genetic codes are obtained by maximizing the number of physio-chemically similar amino acids assigned to evolutionarily similar codons. Formulating genetic code as a Traveling Salesman Problem (TSP) with amino acids as “cities” and codons as “tour positions” and implemented with a Hopfield neural network, the unsupervised learning algorithm efficiently finds an abundance of genetic codes that are more error-minimizing than SGC. Drawing evidence from molecular phylogenies of contemporary tRNAs and aminoacyl-tRNA synthetases, we show that co-diversification between gene sequences and gene functions, which cumulatively captures functional differences with sequence differences and creates a genomic “memory” of the living environment, provides the biological basis for the Hebbian learning algorithm. Like the Hebb’s rule, the locally acting phylogenetic learning rule, which may simply be stated as increasing phylogenetic divergence for increasing functional difference, could lead to complex and robust life systems. Natural selection, while essential for maintaining gene function, is not necessary to act at system levels. For molecular systems that are self-organizing through phylogenetic learning, the TSP model and its Hopfield network solution offer a promising framework for simulating emerging behavior, forecasting evolutionary trajectories, and designing optimal synthetic systems.

A numerical technique for modeling the soil as a two-phase medium by means of a user material subroutine is presented. The approach is applied to a classical FE analysis in a Lagrangian formulation using an explicit time integration rule and to a Coupled Eulerian–Lagrangian approach. The application of these two approaches to the problem of pile jacking into fully saturated soil under partially drained conditions is investigated and compared to the solution obtained by use of an iterative equation solver. The influence of the installation process as well as the influence of the permeability on the surrounding soil is investigated.

The lithium-air (Li-air) battery, shown schematically in Fig. 1, with its usable energy density close to 1,700Wh/kg has captured worldwide attention as a promising battery solution for electric vehicles. However, a major hurdle facing the development of Li-air systems is their poor round-trip efficiency owing to the formation of electrically insulating lithium peroxide (Li2O2) at the cathode surface. Although it is well known that Li2O2 inhibits the reduction process during cell charging, how the deposition morphology of Li2O2 affects the cell performance is poorly understood. Ex-situ imaging has shown that the Li-air cathodes have highly intricate structures and the deposition of Li2O2 is equally complex. However, all existing simulations thus far treat the electrode/Li2O2 matrix as a homogenous continuum and utilize simply-shaped electrode morphologies, such as spheres and rods, to construct volume-averaged expressions (see Fig. 2a) for porosity and surface area. The formation of Li2O2 is then modeled as growing uniformly above these simplified electrodes, and manifests merely as a change in bulk porosity. Such assumptions are insufficient in characterizing the precise effect of the complex electrode/Li2O2microstructure on cell performance. In this paper, we present a pore-scale transport resolved model (see Fig. 2b) of the Li-air battery that fully accounts for the electrode microstructure and peroxide growth. This approach requires no empirical correlations regarding the electrode morphology. Additionally, the growth of Li2O2 is modeled locally and no longer requires the assumption of uniform deposition. Utilizing this pore-scale transport resolved model, the complex electrode and Li2O2 morphologies can be directly incorporated into the numerical model and their effects on system-level performance can be evaluated. Incorporating the thickness-dependent electron resistivity and rate-dependent growth morphology of Li2O2, results obtained from our pore-scale model agree well with experiments. The validated model is then used to predict the galvanostatic discharge behavior of a Li-air cell for a variety of electrode/Li2O2 morphologies. The effects of pore-size (e.g., macro-, meso-, and micro-pores), electrode structure, discharge/charge rate, and oxygen solubility on Li2O2 growth and cell performance are presented. Figure 3 shows the cell voltage versus specific capacity curves for electrodes with different microstructures. The model presented here will be a valuable tool for rational design of electrode microstructures for improved cell performance.

To investigate the potential role of interleukin-18 (IL-18) in immunomodulation during tumorigenesis of esophageal carcinoma and elucidate the underlying molecular mechanism, we employed IL-18 knockout mice for this purpose. Carcinogen 4-nitroquinoline 1-oxide (4NQO) was administrated in drinking water to induce occurrence of esophageal squamous cell carcinoma (ESCC). T cell activation as indicated by the surface CD molecules was analyzed with flow cytometry. The serous content of interferon-γ (IFN-γ) along with other cytokines was determined by inflammatory human cytokine cytometric bead array. The cytotoxicity assay was performed by co-culture of tumor cells with immune cells and relative cell viability was determined by lactate dehydrogenase (LDH) assay. Apoptotic cells were stained with Annexin-V/propidium iodide (PI) and analyzed by flow cytometry. Cell proliferation was measured with Cell Counting Kit-8 (CCK-8) assay. Our data demonstrated that deficiency of IL-18 promoted the progression and development of 4NQO-induced ESCC. Loss of IL-18 suppressed the activation of T cells in the esophagus. Deficiency of IL-18 inhibited the IFN-γ production by CD8

Selenium has attracted intensive attention as a promising material candidate for future optoelectronic applications. However, selenium has a strong tendency to grow into nanowire forms due to its anisotropic atomic structure, which has largely hindered the exploration of its potential applications. In this work, using a physical vapor deposition method, we have demonstrated the synthesis of large-size, high-quality 2D selenium nanosheets, the minimum thickness of which could be as thin as 5 nm. The Se nanosheet exhibits a strong in-plane anisotropic property, which is determined by angle-resolved Raman spectroscopy. Back-gating field-effect transistors based on a Se nanosheet exhibit p-type transport behaviors with on-state current density around 20 mA/mm at Vds = 3 V. Four-terminal field effect devices are also fabricated to evaluate the intrinsic hole mobility of the selenium nanosheet, and the value is determined to be 0.26 cm2 Vs at 300 K. The selenium nanosheet phototransistors show an excellent photoresponsivity of up to 263 A/W, with a rise time of 0.1 s and fall time of 0.12 s. These results suggest that crystal selenium as a 2D form of a 1D van der Waals solid opens up the possibility to explore device applications., Comment: ACS Nano, 2017, 11 (10), pp 10222

The present study evaluated the distribution of sympathetic and parasympathetic nerves and the expression of the α9 nicotinic acetylcholine receptor (α9nAChR) and investigated their potential association with colorectal cancer (CRC) development. The distribution of autonomic nerves and α9nAChR in CRC was detected by immunohistochemistry, which was then used to analyze their association with clinicopathological parameters and prognosis. Sympathetic fibers were primarily observed in the stroma adjacent to cancer cells, whereas parasympathetic fibers were primarily observed in the stroma away from cancer cells. Patients with samples positive for sympathetic nerve fibers had less lymph node invasion and a better prognosis compared with patients with samples negative for sympathetic nerve fibers. The expression of parasympathetic nerves in patients >60 years old was increased compared with patients ≤60 years old. The expression of parasympathetic nerves in patients with lymph node invasion was increased compared with patients without lymph node invasion. The detection of parasympathetic nerves gradually increased as CRC (T stage) advanced. Patients with parasympathetic negative samples had better prognoses compared with patients with parasympathetic positive samples. The expression of α9nAChR was principally localized in cellular membranes and the cytoplasm of CRC tissues and it was revealed to have a positive association with the number of parasympathetic nerves. Increased α9nAChR expression was observed in patients >60 years old compared with patients

Few-layer black phosphorus (BP) has emerged as one of the most promising candidates for post-silicon electronic materials due to its outstanding electrical and optical properties. However, lack of large-scale BP thin films is still a major roadblock to further applications. The most widely used methods for obtaining BP thin films are mechanical exfoliation and liquid exfoliation. Herein, a method of directly synthesizing continuous BP thin films with the capability of patterning arbitrary shapes by employing ultrafast laser writing with confinement is reported. The physical mechanism of confined laser metaphase transformation is understood by molecular dynamics simulation. Ultrafast laser ablation of BP layer under confinement can induce transient nonequilibrium high-temperature and high-pressure conditions for a few picoseconds. Under optimized laser intensity, this process induces a metaphase transformation to form a crystalline BP thin film on the substrate. Raman spectroscopy, atomic force microscopy, and transmission electron microscopy techniques are utilized to characterize the morphology of the resulting BP thin films. Field-effect transistors are fabricated on the BP films to study their electrical properties. This unique approach offers a general methodology to mass produce large-scale patterned BP films with a one-step manufacturing process that has the potential to be applied to other 2D materials.

Bacteria of many species rely on a simple molecule, the intracellular secondary messenger c-di-GMP (Bis-(3'-5')-cyclic dimeric guanosine monophosphate), to make a vital choice: whether to stay in one place and form a biofilm, or to leave it in search of better conditions. The c-di-GMP network has a bow-tie shaped architecture that integrates many signals from the outside world—the input stimuli—into intracellular c-di-GMP levels that then regulate genes for biofilm formation or for swarming motility—the output phenotypes. How does the ‘uninformed’ process of evolution produce a network with the right input/output association and enable bacteria to make the right choice? Inspired by new data from 28 clinical isolates of Pseudomonas aeruginosa and strains evolved in laboratory experiments we propose a mathematical model where the c-di-GMP network is analogous to a machine learning classifier. The analogy immediately suggests a mechanism for learning through evolution: adaptation though incremental changes in c-di-GMP network proteins acquires knowledge from past experiences and enables bacteria to use it to direct future behaviors. Our model clarifies the elusive function of the ubiquitous c-di-GMP network, a key regulator of bacterial social traits associated with virulence. More broadly, the link between evolution and machine learning can help explain how natural selection across fluctuating environments produces networks that enable living organisms to make sophisticated decisions., Author summary How does evolution shape living organisms that seem so well adapted that they could be intelligently designed? Here, we address this question by analyzing a simple biochemical network that directs social behavior in bacteria; we find that it works analogously to a machine learning algorithm that learns from data. Inspired by new experiments, we derive a model which shows that natural selection—by favoring biochemical networks that maximize fitness across a series of fluctuating environments—can be mathematically equivalent to training a machine learning model to solve a classification problem. Beyond bacteria, the formal link between evolution and learning opens new avenues for biology: machine learning is a fast-moving field and its many theoretical breakthroughs can answer long-standing questions in evolution.

Experimental demonstrations of one-dimensional (1D) van der Waals material tellurium (Te) have been presented by Raman spectroscopy under strain and magneto-transport. Raman spectroscopy measurements have been performed under strains along different principle axes. Pronounced strain response along the c-axis is observed due to the strong intrachain covalent bonds, while no strain response is obtained along the a-axis due to the weak interchain van der Waals interaction. Magneto-transport results further verify its anisotropic property, which results in dramatically distinct magneto-resistance behaviors in terms of three different magnetic field directions. Specifically, phase coherence length extracted from weak antilocalization effect, Lϕ ≈ T–0.5, claims its two-dimensional (2D) transport characteristics when an applied magnetic field is perpendicular to the thin film. In contrast, Lϕ ≈ T–0.33 is obtained from universal conductance fluctuations once the magnetic field is along the c-axis of Te, which ind...

Tibial dyschondroplasia (TD) is an intractable poultry problem that is characterized by the appearance of non-vascularized and non-mineralized cartilage masses in tibial growth plates (TGPs). However, the role of angiogenesis inhibition in the occurrence of TD remains unknown. In this study, we found that, compared to low-altitude Arbor Acres chickens (AACs), high-altitude Tibetan chickens showed higher tibial vascular distributions that were accompanied by up-regulation of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGFA) and VEGF receptors. These observations provide insights into hypoxia-induced angiogenesis, which may be related to the absence of TD in high-altitude native Tibetan chickens. Importantly, hypoxia experiments also showed that during hypoxia, tibial angiogenesis was enhanced, which was due to pro-angiogenic factor up-regulation (including VEGFA, VEGFR1, VEGFR2, and IL-8), in AACs. Moreover, we observed that thiram-induced TD could strongly inhibit tibial angiogenesis in the hypertrophic zone through coordinated down-regulation of HIF-1α and pro-angiogenic factors, leading to a disruption in the blood supply to the TGP. Taken together, these findings reveal that the occurrence of TD is highly associated with inhibition of tibial angiogenesis through down-regulated expression of HIF-1α, VEGFA and VEGF receptors, which results in suppression of TGP development.

The so-called Boltzmann tyranny defines the fundamental thermionic limit of the subthreshold slope of a metal-oxide-semiconductor field-effect transistor (MOSFET) at 60 mV dec

We have demonstrated that depletion/enhancement-mode b-Ga2O3 on insulator field-effect transistors can achieve a record high drain current density of 1.5/1.0 A/mm by utilizing a highly doped b-Ga2O3 nano-membrane as the channel. b-Ga2O3 on insulator field-effect transistor (GOOI FET) shows a high on/off ratio of 1010 and low subthreshold slope of 150 mV/dec even with 300 nm thick SiO2. The enhancement-mode GOOI FET is achieved through surface depletion. An ultra-fast, high resolution thermo-reflectance imaging technique is applied to study the self-heating effect by directly measuring the local surface temperature. High drain current, low Rc, and wide bandgap make the b-Ga2O3 on insulator field-effect transistor a promising candidate for future power electronics applications.

Tibial dyschondroplasia (TD) is one of the most common problems in the poultry industry and leads to lameness by affecting the proximal growth plate of the tibia. However, due to the unique environmental and geographical conditions of Tibet, no case of TD has been reported in Tibetan chickens (TBCs). The present study was designed to investigate the effect of high altitude hypoxia on blood parameters and tibial growth plate development in chickens using the complete blood count, morphology, and histological examination. The results of this study showed an undesirable impact on the overall performance, body weight, and mortality of Arbor Acres chickens (AACs) exposed to a high altitude hypoxic environment. However, AACs raised under hypoxic conditions showed an elevated number of red blood cells (RBCs) and an increase in hemoglobin and hematocrit values on day 14 compared to the hypobaric normoxia group. Notably, the morphology and histology analyses showed that the size of tibial growth plates in AACs was enlarged and that the blood vessel density was also higher after exposure to the hypoxic environment for 14 days, while no such change was observed in TBCs. Altogether, our results revealed that the hypoxic environment has a potentially new role in increasing the blood vessel density of proximal tibial growth plates to strengthen and enhance the size of the growth plates, which may provide new insights for the therapeutic manipulation of hypoxia in poultry TD.

According to retaining walls of joint construction buildings and office building of the mine of three yuan weizi town, outdoor pavement reinforcement of engineering practice, introduced the design parameters and construction process of the high-pressure jet grouting pile, soil nail wall and drilling grouting, the results showed that reinforcement scheme is reasonable and feasible, there is reference to other similar projects.

Borrelia burgdorferi sensu lato (B. burgdorferi s.l.), the group of bacterial species represented by Lyme disease pathogens, has one of the most complex and variable genomic architectures among prokaryotes. Showing frequent recombination within and limited gene flow among geographic populations, the B. burgdorferi s.l. genomes provide an excellent window into the processes of bacterial evolution at both within- and between-population levels. Comparative analyses of B. burgdorferi s.l. genomes revealed a highly dynamic plasmid composition but a conservative gene repertoire. Gene duplication and loss as well as sequence variations at loci encoding surface-localized lipoproteins (e.g., the PF54 genes) are strongly associated with adaptive differences between species. There are a great many conserved intergenic spacer sequences that are candidates for cis-regulatory elements and non-coding RNAs. Recombination among coexisting strains occurs at a rate approximately three times the mutation rate. The coexistence of a large number of genomic groups within local B. burgdorferi s.l. populations may be driven by immune-mediated diversifying selection targeting major antigen loci as well as by adaptation to multiple host species. Questions remain regarding the ecological causes (e.g., climate change, host movements, or new adaptations) of the ongoing range expansion of B. burgdorferi s.l. and on the genomic variations associated with its ecological and clinical variability. Anticipating an explosive growth of the number of B. burgdorferi s.l. genomes sampled from both within and among species, we propose genome-based methods to test adaptive mechanisms and to identify molecular bases of phenotypic variations. Genome sequencing is also necessary for monitoring a likely increase of genetic admixture of previously isolated species and populations in North America and elsewhere.

To assess the prevalence of decreased glomerular filtration rate (GFR) in Tibetan children with congenital heart disease (CHD) and its associated risk factors. A total of 207 Tibetan children attending authors’ center for treatment of CHD from May 2012 through November 2012, were included in the study. GFR was estimated with the Schwartz formula (eGFR). The mean eGFR was 104.3 ± 16.6 mL/min/1.73 m2, and decreased in 21 children (10.1 %). In the cyanotic category, eGFR was decreased only in severely cyanotic individuals. In the acyanotic category with left ventricular overload, children with decreased eGFR were younger, more commonly lived in areas above 4,700 m, and had higher left ventricular internal dimensions indexed by body surface areas (LVID/BSA) (53.8 ± 6.9 vs. 40.1 ± 6.8 mm/m2, P

The Standard Genetic Code (SGC) is robust to mutational errors such that frequently occurring mutations minimally alter the physio-chemistry of amino acids. The apparent correlation between the evolutionary distances among codons and the physio-chemical distances among their cognate amino acids suggests an early co-diversification between the codons and amino acids. Here we formulated the co-minimization of evolutionary distances between codons and physio-chemical distances between amino acids as a Traveling Salesman Problem (TSP) and solved it with a Hopfield neural network. In this unsupervised learning algorithm, macromolecules (e.g., tRNAs and aminoacyl-tRNA synthetases) associating codons with amino acids were considered biological analogs of Hopfield neurons associating "tour cities" with "tour positions". The Hopfield network efficiently yielded an abundance of genetic codes that were more error-minimizing than SGC and could thus be used to design artificial genetic codes. We further argue that as a self-optimization algorithm, the Hopfield neural network provides a model of origin of SGC and other adaptive molecular systems through evolutionary learning.

The thirst for novel two-dimensional (2D) materials for ultra-scaled electronics keeps growing during the last decade as the downsizing trend of silicon-based conventional semiconductors is approaching its physical limit. An ideal paradigm of 2D materials suitable for logic device applications should possess high carrier mobility for both type of carriers, good air-stability, controllable doping scheme and a reasonable bandgap. Recently reported hydrothermal growth technique of 2D tellurium (Te) thin films, which meet all the above criteria, offers a new option for 2D material-based CMOS applications. Tellurium is a narrow bandgap p-type semiconductor (0.35 eV) with nearly symmetric mobilities for both electrons and holes of around 700 cm2/Vs at room temperature. It has one-dimensional chiral crystal structure and can be grown into 2D films under right conditions. Just like other 2D materials, these 2D facets of Te also contain no dangling bonds and therefore the 2D films can preserve the material properties and have great potential for miniaturizing device geometry in principle. Here we first report systematic investigation of 2D Te p-type transistor performance approaching atomic-thin limit. The device key parameters, such as field-effect mobility, on/off ratio and stability were thoroughly studied as a function of film thickness. The device performance was then optimized through contact and dielectric engineering, and large drive current over 1 A/mm was achieved. We further employed photo-current mapping method to show that rare accumulation-type ohmic contacts were formed using high work function metal (palladium). Finally, we present an atomic layer deposited (ALD) dielectric doping technique to effectively dope the intrinsically p-type channel into n-type with almost symmetric operations for both NMOS and PMOS. Prototypical inverters based on Te CMOS demonstrate great potential of constructing Te-based high-speed CMOS logic circuits. Our work not only established a comprehensive guideline for designing and optimizing 2D Te based CMOS devices, but also provided a device platform to explore versatility of 2D Te from many other perspectives, such as condensed matter physics and thermoelectronics.

Candida species is an important cause of nosocomial infection in neonatal intensive care units (NICUs). However, most reports in China have been limited to single institutions. The aim of this study is to investigate the epidemiology of invasive candidiasis in multiple NICUs across China.We retrospectively collected demographic data, clinical characteristics, microbiological results and outcome of preterm infants with invasive candidiasis discharged from 11 academic tertiary NICUs during January 2009 to December 2011.There were 30,045 preterm infants discharged from 11 NICUs during the study period. We detected 223 infants with invasive candidiasis, resulting in an incidence of 0.74 cases per 100 preterm discharges from NICUs. In very low birth weight infants, the incidence was 3.42 cases per 100 very low birth weight discharges. Mean gestational age of infected infants was 31.4 weeks and median birth weight was 1410 gram. Among the cohort of infants with invasive candidiasis, 214 (96.0%) infants had positive blood culture for fungus, 5 infants had positive urine culture, 3 from cerebrospinal fluid and 1 from articular effusion in the shoulder joint. Among the cohort of infants with candidemia, 48 (22.4%) infants had fungal meningitis. Candida albicans accounted for 57.4% of total positive cultures. Overall mortality attributable to invasive candidiasis was 19.3%.Invasive candidiasis is a common problem among preterm neonates in China, especially among very low birth weight infants and it is associated with a high mortality. The preponderance of infections was due to Candida albicans.

Bei der Bemessung einer Kaikonstruktion ist die Berechnung des aktiven Erddrucks hinter einer Spundwand eine haufige Fragestellung. Messungen und FE-Analysen haben gezeigt, dass der Erddruck auf die vordere Spundwand durch die Verdubelung des Bodenkorpers von den hinter der Spundwand stehenden Pfahlreihen abgeschirmt wird. Bei den konventionellen Berechnungen wird die Verdubelungswirkung der Pfahlreihen rechnerisch durch eine Erhohung des Reibungswinkels berucksichtigt. Mittels eines kleinmasstablichen Versuchsstandes, der am Institut fur Geotechnik und Baubetrieb der TU Hamburg-Harburg steht, werden Erkenntnisse uber den Mechanismus der Erddruckabschirmung gewonnen. Abschliesend wird ein Ansatz zur Evaluation der Erddruckabschirmung vorgestellt. Active earth pressure shielding in quay wall constructions: physical modeling and an analytical approach Designing a quay wall construction the calculation of the active earth pressure behind the sheet pile wall is often a problem. Measurements and FE-analyses have shown that the earth pressure is shielded from the sheet pile wall due to the dowel effect of the pile rows behind the sheet piling. In conventional calculations a higher friction angle is used to take the dowel effect into account. Small-scaled model tests have been carried out to investigate the failure mechanisms of the earth pressure shielding. Based on the results an analytical approach is developed to estimate the shielding effect of the pile rows.

In order to study the influence of settlement under gas pressure in bioreactor landfill, the landfill is simplified as a one-way gas seepage field, combining Darcy’s Law, the gas equation of state, and the principle of effective stress and fluid dynamics of porous media theory. First assume that the bioreactor landfill leachate is fully recharged on the basis of gas mass conservation, then according to the changes in gas pressure (inside the landfill and surrounding atmosphere) during the gas leakage time and settlement in the landfill, establish a numerical model of bioreactor landfill settlement under the action of the gas pressure, and use the finite difference method to solve it. Through a case study, the model’s improved prediction of the settlement of bioreactor landfill is demonstrated.

Enzootic pneumonia (EP), often caused by Mycoplasma hyopneumoniae, occurs in Tibetan pigs between October and December in Western China. The aim of this study was to determine the prevalence of M. hyopneumoniae in Tibetan pig herds and also the prevalence of infection. M. hyopneumoniae was detected using enzyme-linked immunosorbent assay, polymerase chain reaction (PCR), and 16S rRNA sequencing. Twenty-nine inflammatory gross-lesions were observed in 155 lungs of slaughtered pigs. Invasion of focal lymphocytes was confirmed by paraffin sectioning and hematoxylin-eosin staining of lung sections. Bronchoalveolar lavage fluid (BALF) from slaughtered Tibetan pigs and nasal swabs from others were assayed using PCR. The prevalence of M. hyopneumoniae in Tibetan pig herds (via ELISA) was 20.48% (93/454) in 3 provinces (Sichuan, Tibet autonomous region, and Qinghai) between October and December of 2014. The difference in prevalence among animals in six different growing stages was statistically significant (P

Tibial dyschondroplasia (TD) cases has not been reported in Tibetan chickens (TBCs), but it is commonly seen in commercial broilers characterized by lameness. The underlying mechanism remains unclear. Hypoxia-inducible factors (HIFs) are important regulators of cellular adaptation to hypoxic conditions. In this study, we investigated the role of HIF-1α, -2α, and -3α in hypoxia and thiram-induced TD and their effect on tibial growth plate development in Arbor Acres chickens (AACs) and TBCs. RNA and protein expression levels of HIF-1α, -2α, and -3α were determined by using quantitative reverse transcriptase polymerase chain reaction and western blotting analyses, respectively. Interestingly, the results showed that HIF-1α, -2α, and -3α expressions in the tibial growth plate of TBCs were upregulated by hypoxia and the change was more significant in TBCs than in AACs. However, these factors were downregulated in thiram-induced TD. To further clarify the effect of thiram on tibial growth plate in commercial broilers, AACs were observed to exhibit more pronounced changes in their growth plate that that in TBCs. Taken together, these results demonstrate that HIF-1α, -2α, and -3α may be important in tibial growth plate development and in the prevention of TD. The present study contributes novel insights on a therapeutic target for poultry TD.

Over 80% of triple negative breast cancers express mutant p53. Mutant p53 often gains oncogenic function suggesting that triple negative breast cancers may be driven by p53 protein type. To determine the chromatin targets of this gain-of-function mutant p53 we used inducible knockdown of endogenous gain-of-function mtp53 in MDA-MB-468 cells in conjunction with stable isotope labeling with amino acids in cell culture and subcellular fractionation. We sequenced over 70,000 total peptides for each corresponding reciprocal data set and were able to identify 3010 unique cytoplasmic fraction proteins and 3403 unique chromatin fraction proteins. The present proteomics experiment corroborated our previous experiment-based results that poly ADP-ribose polymerase has a positive association with mutant p53 on the chromatin. Here, for the first time we report that the heterohexomeric minichromosome maintenance complex that participates in DNA replication initiation ranked as a high mutant p53-chromatin associated pathway. Enrichment analysis identified the minichromosome maintenance members 2–7. To validate this mutant p53- poly ADP-ribose polymerase-minichromosome maintenance functional axis, we experimentally depleted R273H mutant p53 and found a large reduction of the amount of minichromosome maintenance complex proteins on the chromatin. Furthermore a mutant p53-minichromosome maintenance 2 direct interaction was detected. Overexpressed mutant p53, but not wild type p53, showed a protein-protein interaction with minichromosome maintenance 2 and minichromosome maintenance 4. To target the mutant p53- poly ADP-ribose polymerase-minichromosome maintenance axis we treated cells with the poly ADP-ribose polymerase inhibitor talazoparib and the alkylating agent temozolomide and detected synergistic activation of apoptosis only in the presence of mutant p53. Furthermore when minichromosome maintenance 2–7 activity was inhibited the synergistic activation of apoptosis was blocked. This mutant p53- poly ADP-ribose polymerase -minichromosome maintenance axis may be useful for theranostics., Personalized medicine: Mutated tumors respond to therapy Mutations in the p53 tumor suppressor gene could offer a predictive biomarker of response to certain drugs in triple-negative breast cancer. Jill Bargonetti from Hunter College in New York, USA, and colleagues showed that mutant p53, which is expressed in more than 80% of patients with triple-negative breast cancer, interacts with and regulates hundreds of proteins, including those found in a complex needed for DNA replication. Members of this complex, called the minichromosome maintenance protein complex, interact with mutant p53—but less with wild-type p53. Bargonetti’s team targeted this pathway in mutated breast cancer cells with the PARP inhibitor talazoparib and the chemotherapeutic agent temozolomide. They observed synergistic cell killing with the two drugs, but only when the minichromosome maintenance protein complex was working and when p53 was mutated. These findings point toward a new strategy for personalizing therapy.

The reliable production of two-dimensional (2D) crystals is essential for the development of new technologies based on 2D materials. However, current synthesis methods suffer from a variety of drawbacks, including limitations in crystal size and stability. Here, we report the fabrication of large-area, high-quality 2D tellurium (tellurene) using a substrate-free solution process. Our approach can create crystals with process-tunable thickness, from a monolayer to tens of nanometres, and with lateral sizes of up to 100 µm. The chiral-chain van der Waals structure of tellurene gives rise to strong in-plane anisotropic properties and large thickness-dependent shifts in Raman vibrational modes, which is not observed in other 2D layered materials. We also fabricate tellurene field-effect transistors, which exhibit air-stable performance at room temperature for over two months, on/off ratios on the order of 106, and field-effect mobilities of about 700 cm^2 V^(−1) s^(−1). Furthermore, by scaling down the channel length and integrating with high-k dielectrics, transistors with a significant on-state current density of 1 A mm^(−1) are demonstrated.

The so-called Boltzmann Tyranny defines the fundamental thermionic limit of the subthreshold slope (SS) of a metal-oxide-semiconductor field-effect transistor (MOSFET) at 60 mV/dec at room temperature and, therefore, precludes the lowering of the supply voltage and the overall power consumption. Adding a ferroelectric negative capacitor to the gate stack of a MOSFET may offer a promising solution to bypassing this fundamental barrier. Meanwhile, two-dimensional (2D) semiconductors, such as atomically thin transition metal dichalcogenides (TMDs) due to their low dielectric constant, and ease of integration in a junctionless transistor topology, offer enhanced electrostatic control of the channel. Here, we combine these two advantages and demonstrate for the first time a molybdenum disulfide (MoS2) 2D steep slope transistor with a ferroelectric hafnium zirconium oxide layer (HZO) in the gate dielectric stack. This device exhibits excellent performance in both on- and off-states, with maximum drain current of 510 {\mu}A/{\mu}m, sub-thermionic subthreshold slope and is essentially hysteresis-free. Negative differential resistance (NDR) was observed at room temperature in the MoS2 negative capacitance field-effect-transistors (NC-FETs) as the result of negative capacitance due to the negative drain-induced-barrier-lowering (DIBL). High on-current induced self-heating effect was also observed and studied., Comment: 23 pages, 14 figures

Toxoplasma gondii (T. gondii) is one of the most common and widespread protozoan parasite which caused toxoplasma infection in animals and humans. Toxoplasma infection in healthy people is usually asymptomatic and it can lead to serious pathological effects in congenital cases and immunodeficient patients. The aim of the study is to investigate the prevalence of T. gondii infection in native Tibetans in Tibet as scarce information is available on such a high plateau. A total of 600 blood samples were collected from Tibetans people who visited the hospital in Nyingchi city with the history of flu, swollen lymph glands, muscle pain, and neurological or eyes complications (showing single or more signs). The serum of collected samples were tested for IgG antibody by ELISA. The result showed that the prevalence in men and women were 11.3% and 11.0%, respectively, the prevalence in different ages were 9.8% in < 7 years, 6.2% in ≥7-17 years, 10.1% in ≥18-40 years, 14.8% in ≥41-65 years and 11.6% in ≥66 years. The current study indicates the first report of this zoonotic parasite infection in Tibetan people.

We previously found that endoplasmic reticulum stress (ERS) might be exhibited in the conventional protocol of the primary culture of neonate rat myocardial cells (NRMCs) and that the high glucose concentration (25 mmol/L) in the culture medium might be the cause. Here, we investigated if the high concentration of glucose might influence ERS in myocardial cells during culture. GRP78 expression (ERS marker) was similar in groups with tunicamycin (TM) and without TM in high glucose cultured cells (p > 0.01). Different glucose concentrations elicited different GRP78 expressions according to analyses of protein and RNA levels, which showed ERS in H/H groups. Finally, we found that GRP78 expression was higher in TM groups compared with M/M groups (p < 0.01). The conventional high-glucose culture media during primary culture of NRMCs induced ERS. We propose that medium-glucose culture media should be used and describe an improved protocol for the primary culture of NRMCs.

Transition metal pentatelluride ZrTe

In this paper, high-performance few-layer black phosphorus (BP) PMOSFETs have been demonstrated by using MOCVD BN and ALD Al 2 O 3 as the top-gate dielectric as well as the passivation layer. Highest Ion of 850μA/μm (V ds = −1.8 V) and g m of 340μS/μm (Vds = −0.8 V) have been achieved with the 200nm chancel length (L ch ) devices. Record low contact resistance (R c ) of 0.58kΩ·μm has been obtained on BP transistors by contact engineering. The gate leakage of the BN/Al 2 O 3 bilayer gate dielectric is less than 10−12A/μm2 (V g = −1V) with an EOT of 3nm. SS and hysteresis voltage as low as 70mV/dec and 0.1V have been achieved, indicating a high quality interface between BP and BN.

Thiamin pyrophosphate (ThDP), the active form of thiamin (vitamin B1), is believed to be an essential cofactor for all living organisms1,2. Here, we report the unprecedented result that thiamin is dispensable for the growth of the Lyme disease pathogen Borrelia burgdorferi (Bb)3. Bb lacks genes for thiamin biosynthesis and transport as well as known ThDP-dependent enzymes4, and we were unable to detect thiamin or its derivatives in Bb cells. We showed that eliminating thiamin in vitro and in vivo using BcmE, an enzyme that degrades thiamin, has no impact on Bb growth and survival during its enzootic infectious cycle. Finally, high-performance liquid chromatography analysis reveals that the level of thiamin and its derivatives in Ixodes scapularis ticks, the enzootic vector of Bb, is extremely low. These results suggest that by dispensing with use of thiamin, Borrelia, and perhaps other tick-transmitted bacterial pathogens, are uniquely adapted to survive in tick vectors before transmitting to mammalian hosts. To our knowledge, such a mechanism has not been reported previously in any living organisms.

Background: Over the last few years, probiotics have been one of the most studied interventions in neonatal medicine. Objectives: The aim of this work was to analyse all studies (randomized controlled trials, RCTs, and observational studies) assessing the use of probiotics in very low birth weight (VLBW) preterm infants. Search Methods: A systematic literature search was conducted using PubMed, Embase, Cochrane Library, and Web of Science. The data from RCTs and observational studies were pooled and analysed separately. Selection Criteria: RCTs and observational studies that enrolled VLBW infants with enteral administration of probiotics were considered. Extracted study data included probiotic characteristics and at least 1 clinical outcome (necrotizing enterocolitis [NEC], late-onset sepsis or all-cause mortality). Data Collection and Analysis: Forty-four studies were eligible for our review: 30 RCTs and 14 observational studies. Severe NEC rates (stage II or more) and all-cause mortality were reduced among the probiotic groups in both the RCTs (RR 0.57, 95% CI 0.47-0.70, and RR 0.77, 95% CI 0.65-0.92, respectively) and the observational studies (RR 0.51, 95% CI 0.37-0.70, and RR 0.71, 95% CI 0.62-0.81, respectively). Furthermore, there was a 12% reduction in the risk of sepsis in RCTs and a 19% reduction in observational studies. The meta-analysis of observational studies showed a reduction in the risk of NEC in extremely low birth weight infants. However, this was not statistically significant. Conclusions: This meta-analysis of RCT and observational studies found that the use of probiotics was beneficial for the prevention of severe NEC, late-onset sepsis, and all-cause mortality in VLBW infants.

Background The purpose of this study was to investigate whether uncovertebral joint ossification was a risk factor for axial symptoms (AS) after cervical disc arthroplasty (CDA). Methods This retrospective study included 52 consecutive patients who underwent CDA for single-level cervical disc disease. To examine possible risk factors for AS after CDA, univariate and multivariate logistic regression analyses were conducted to compare data from the patients with and without AS (the AS and no-AS groups, respectively). Results Among the 52 patients examined, AS were observed in 24 patients (46.2 %), including a stiff neck (n = 11), neck pain and dullness (n = 10), and shoulder pain (n = 3). Uncovertebral joint ossification was detected in 22 (42.3 %) patients, including 17 patients in the AS group and 5 patients in the no-AS group. Clinical outcome improved during the follow-up period for the AS group. According to multivariate logistic regression analysis, uncovertebral joint ossification, cervical kyphosis, and range of motion (ROM) at the index level were identified as significant risk factors for AS after CDA. Conclusions Satisfactory clinical outcomes were observed following CDA for the treatment of single-level cervical disc disease in the present cohort. In addition, uncovertebral joint ossification, cervical kyphosis, and ROM at the index level were found to affect the incidence of AS after CDA.

Fur die Errichtung von Windparks ist der Einsatz von Offshore-Hubplattformen Stand der Technik. Die Hubplattform installiert sich vor dem eigentlichen Arbeiten auf dem Meeresgrund, um ausreichende Stabilitat fur die Arbeiten zu haben und den Einfluss des Seegangs zu minimieren. Eine mogliche Grundungsvariante fur die Beine einer Offshore-Hubplattform ist die sogenannte Spudcan-Losung. Hierbei wird ein Kreisfundament mit grosem Durchmesser am Bein der Hubplattform befestigt, uber das die Grundungslasten abgetragen werden. Der Einsatz derartiger Grundungen ist im internationalen Ol- und Gasbereich gangig und erprobt. Dennoch ist bereits die korrekte Bemessung der vertikalen Tragfahigkeit der Spudcans komplex. So ist zum Beispiel die Bestimmung der Last-Setzungskurve bei unterschiedlichen Baugrundverhaltnissen schwierig und die Definition der “sicheren Seite” ebenfalls nicht eindeutig. Ein weiteres Problem, welches bei Absetzen auf geschichtetem Baugrund auftreten kann, ist der sogenannte “punch-through”, d. h. bei beispielsweise dicht gelagertem Sand uber weichem Boden kann es zu einem plotzlichen Durchstanzen der Plattform in die Weichschicht kommen, was bis hin zum Verlust der Plattform fuhren kann. In diesem Beitrag werden verschiedene Bemessungsansatze aus der Literatur und internationale Richtlinien zur Bemessung von Spudcans vorgestellt. Zudem werden offene Fragestellungen und Ansatze aus der Forschung diskutiert. Diese sollen dem Leser einen Eindruck uber die Moglichkeiten von Spudcan-Grundungen geben und ihn gleichzeitig fur mogliche Problemstellungen sensibilisieren. Spudcans as foundations for offshore jack-up rigs – Problems and calculation methods For the installation of wind parks jack-up rigs can be used. Jack-up rigs are founded on the seabed before start of operation to receive sufficient stability and to reduce wave induced influences. One possible foundation for jack-up rigs on the seabed is the so-called spudcan. A spudcan is a circular foundation attached to the legs of the jack-up rig to transfer the vertical loads into the ground. The use of spudcan-foundations is state-of-the-art in the oil- and gas industry. Nevertheless, the design of this type of foundation is still challenging. For example, the correct determination of the load-settlement-response with respect to different soil conditions is complex and the definition of the “safe side” is not always clear. Another problem related to the spudcan depositioning onto layered soil is the so-called “punch-through”-failure. This means that during installation onto dense sand overlying weak clay the spudcan may suddenly punch through the sand layer into the weaker layer. This can even lead to a total loss of the jack-up rig. In this contribution, different methods for spudcan design recommended in literature and international guidelines are summarized. Furthermore, open questions and results of ongoing research are discussed to give the reader an impression of the capabilities and the difficulties regarding spudcan foundations.

To improve the production quality of mini-car spoke components, the forming process of mini-car spoke components is numerically simulated by DYNAFORM, and the geometry models of punch, die, blank holder and sheet metal are established, the effect of round-hole flange coefficient, material parameters and forming craft on flanging forming is evaluated by simulation computation method, and the suggestions for improvement are discussed. The results indicates that the increase in material yield strength has a great influence on flanging cracking; and through improving flanging process, the cracking defects of round-hole flanging in the spoke components can be controlled, the cracking rate reduces to 0.1 ‰, and the better product quality can be obtained.

Performing the 3-D numerical modeling of the automobile covering parts by the Pro/E software, creating both addendum and blank holding surfaces, and importing them into the DYNAFORM so that a FEM model can be created. Use the DYNAFORM to perform the simulation calculation and analysis, and study the influences of the factors such as friction coefficient, die clearance and material parameters (n and r values) on the stamping formability. The results show that the parameters such as friction coefficient between die and blank, die clearance and the v value in the material parameters play the key role in the the blank flowability, and have the significant influence on the stamping result.

A 3D pore-scale transport resolved model is used to study the performance characteristics of a vanadium redox flow battery (VRFB) with various electrode morphologies under different operating conditions. Three electrode structures are reconstructed from X-ray computed tomography (XCT) images of porous carbon felt electrode materials. The local vanadium concentration, overpotential, current density and overall cell voltage for the positive half cell are examined. The results indicate that the cell voltage increases with increasing electrolyte flow rate due to decreasing concentration gradients of vanadium species within the porous electrode. However, the marginal gain in cell voltage diminishes once the concentration field approaches uniformity under convection-dominated mass transport conditions at sufficiently high electrolyte flow rates. The model also predicts that electrode structures with low porosity (high surface area) result in more uniform and lower absolute current density and overpotential fields at the expense of increased pressure drop. Finally, poor cell performance is observed for simulations operated at low electrolyte flow rates and low states of charge due to the fuel starvation (i.e., insufficient amount of reactant in the cell).

By designing a quay wall construction the calculation of the active earth pressure behind the sheet pile wall is often a problem. Measurements and FE-analyses have shown that the earth pressure on a sheet pile wall is shielded due to the dowel effect of the pile rows behind the sheet piling. In conventional calculations a higher friction angle is used to take the dowel effect into account. In this study, numerical modeling using the Coupled Eulerian–Lagrangian method has been carried out to investigate the shielding effect of pile rows on the active earth pressure in sand. The failure mechanisms have been illustrated using the shear band patterns at the limit state. Based on the Terzaghi’s arching theory a new approach has been developed to estimate the shielding effect.

The vanadium redox flow battery (VRFB) has emerged as a viable grid-scale energy storage technology that offers cost-effective energy storage solutions for renewable energy applications. In this paper, a novel methodology is introduced for modeling of the transport mechanisms of electrolyte flow, species and charge in the VRFB at the pore scale of the electrodes; that is, at the level where individual carbon fiber geometry and electrolyte flow are directly resolved. The detailed geometry of the electrode is obtained using X-ray computed tomography (XCT) and calibrated against experimentally determined pore-scale characteristics (e.g., pore and fiber diameter, porosity, and surface area). The processed XCT data is then used as geometry input for modeling of the electrochemical processes in the VRFB. The flow of electrolyte through the pore space is modeled using the lattice Boltzmann method (LBM) while the finite volume method (FVM) is used to solve the coupled species and charge transport and predict the performance of the VRFB under various conditions. An electrochemical model using the Butler–Volmer equations is used to provide species and charge coupling at the surfaces of the carbon fibers. Results are obtained for the cell potential distribution, as well as local concentration, overpotential and current density profiles under galvanostatic discharge conditions. The cell performance is investigated as a function of the electrolyte flow rate and external drawing current. The model developed here provides a useful tool for building the structure–property–performance relationship of VRFB electrodes.

The dynamic explicit finite element software DYNAFORM was used to simulate the real and equivalent drawbead model. Analyzed the influence of the blank hold force (BHF) and virtual velocity on blank’s deformation behavior after passing through drawbead, compared the results of the FE simulation. The simulation results were confirmed by experiments. The study shows that the equivalent drawbead model can’t simulate the blank’s behavior precisely when it passing the real drawbeads, the effect of BHF on real drawbead model is larger than equal drawbead model; the proper range of virtual velocity was obtained at the same time.