Cug2 is essential for normal mitotic control and CNS development in zebrafish.

Background: We recently identified a novel oncogene, Cancer-upregulated gene 2 (CUG2), which is essential for kinetochore formation and promotes tumorigenesis in mammalian cells. However, the in vivo function of CUG2 has not been studied in animal models. Results: To study the function of CUG2 in vivo, we isolated a zebrafish homologue that is expressed specifically in the proliferating cells of the central nervous system (CNS). Morpholino-mediated knockdown of cug2 resulted in apoptosis throughout the CNS and the development of neurodegenerative phenotypes. In addition, cug2-deficient embryos contained mitotically arrested cells displaying abnormal spindle formation and chromosome misalignment in the neural plate. Conclusions: Therefore, our findings suggest that Cug2 is required for normal mitosis during early neurogenesis and has functions in neuronal cell maintenance, thus demonstrating that the cug2 deficient embryos may provide a model system for human neurodegenerative disorders

Growth, Reproductive Condition, And Digestive Tubule Atrophy Of Pacific Oyster Crassostrea Gigas In Gamakman Bay Off The Southern Coast Of Korea

Spat of Pacific oysters (Crassostrea gigas) were collected from Gamakman Bay, Korea, and raised in a spat hardening facility located in the low intertidal zone of the bay for a hardening/stunting period of 10 mo. Seasonal changes in growth, reproductive condition, and digestive tubule atrophy (DTA) of these hardened/stunted oysters were monitored for more than a year after transplanting to a suspended longline system in a grow-out area in the bay. After transplantation, the hardened/stunted oysters showed a logarithmic increase in shell size for the first 4 mo, from June to October, and growth remained stable from late fall to early spring. During the 12 mo of the grow-out, the shell size of the hardened/stunted oysters increased from 15.4-74.2 mm, and tissue weight increased from 0.49-12.85 g. Histological analysis revealed that gametogenesis of hardened/stunted oysters commenced as early as February when water temperature remained at 10 degrees C, and spawning occurred from July to September when water temperature reached 25-27 degrees C. DTA assessed from histological analysis was higher from September to February, when the chlorophyll a level in the bay was lower. These data suggest that seasonal fluctuations in water temperature and food availability in the water column are the 2 main environmental parameters governing reproduction and growth of oyster in Gamakman Bay, and DTA could be a useful biomarker for monitoring the nutritional condition of oysters

Large-eddy simulatoin of flow field and pollutant dispession in urban street canyons under unstable atmospheric

Thermal stratification plays an important role in the air flow and pollutant dispersion processes. This study employed a large-eddy simulation (LES) code based on a one-equation subgrid-scale (SGS) model to investigate the flow field and pollutant dispersion characteristics inside urban street canyons. The unstable thermal stratification was simulated by heating the ground level of the street canyons. The thermal buoyancy forces were, using the Boussinesq assumption, taken into account in both the Navier-Stokes equations and the transport equation for SGS turbulent kinetic energy (TKE). The LES had been validated against experimental data obtained in wind tunnel studies before it was applied to study the detailed turbulence and pollutant dispersion characteristics in urban street canyons. The effects of different bulk Richardson number (Rb) were investigated. Several typical temperature differences between the street bottom and ambient air were configured to simulate the scenarios occurring at different times during the day.postprintThe 7th International Conference of Urban Climate (ICUC-7), Yokohama, Japan, 29 June-3 July 2009

Stabilizing multiple topological fermions on a quantum computer

AbstractIn classical and single-particle settings, non-trivial band topology always gives rise to robust boundary modes. For quantum many-body systems, however, multiple topological fermions are not always able to coexist, since Pauli exclusion prevents additional fermions from occupying the limited number of available topological modes. In this work, we show, through IBM quantum computers, how one can robustly stabilize more fermions than the number of topological modes through specially designed 2-fermion interactions. Our demonstration hinges on the realization of BDI- and D-class topological Hamiltonians on transmon-based quantum hardware, and relied on a tensor network-aided circuit recompilation approach. We also achieved the full reconstruction of multiple-fermion topological band structures through iterative quantum phase estimation (IQPE). All in all, our work showcases how advances in quantum algorithm implementation enable noisy intermediate-scale quantum (NISQ) devices to be exploited for topological stabilization beyond the context of single-particle topological invariants.</jats:p

Ultra-strong Adhesion of Graphene Membranes

As mechanical structures enter the nanoscale regime, the influence of van der Waals forces increases. Graphene is attractive for nanomechanical systems because its Young's modulus and strength are both intrinsically high, but the mechanical behavior of graphene is also strongly influenced by the van der Waals force. For example, this force clamps graphene samples to substrates, and also holds together the individual graphene sheets in multilayer samples. Here we use a pressurized blister test to directly measure the adhesion energy of graphene sheets with a silicon oxide substrate. We find an adhesion energy of 0.45 \pm 0.02 J/m2 for monolayer graphene and 0.31 \pm 0.03 J/m2 for samples containing 2-5 graphene sheets. These values are larger than the adhesion energies measured in typical micromechanical structures and are comparable to solid/liquid adhesion energies. We attribute this to the extreme flexibility of graphene, which allows it to conform to the topography of even the smoothest substrates, thus making its interaction with the substrate more liquid-like than solid-like.Comment: to appear in Nature Nanotechnolog

The clinical outcomes of imaging modalities for surgical management Cushing’s disease – A systematic review and meta-analysis

Introduction: Cushing’s disease presents major diagnostic and management challenges. Although numerous preoperative and intraoperative imaging modalities have been deployed, it is unclear whether these investigations have improved surgical outcomes. Our objective was to investigate whether advances in imaging improved outcomes for Cushing’s disease. Methods: Searches of PubMed and EMBASE were conducted. Studies reporting on imaging modalities and clinical outcomes after surgical management of Cushing’s disease were included. Multilevel multivariable meta-regressions identified predictors of outcomes, adjusting for confounders and heterogeneity prior to investigating the effects of imaging. Results: 166 non-controlled single-arm studies were included, comprising 13181 patients over 44 years. The overall remission rate was 77.0% [CI: 74.9%-79.0%]. Cavernous sinus invasion (OR: 0.21 [CI: 0.07-0.66]; p=0.010), radiologically undetectable lesions (OR: 0.50 [CI: 0.37–0.69]; p<0.0001), previous surgery (OR=0.48 [CI: 0.28–0.81]; p=0.008), and lesions ≥10mm (OR: 0.63 [CI: 0.35–1.14]; p=0.12) were associated with lower remission. Less stringent thresholds for remission was associated with higher reported remission (OR: 1.37 [CI: 1.1–1.72]; p=0.007). After adjusting for this heterogeneity, no imaging modality showed significant differences in remission compared to standard preoperative MRI. The overall recurrence rate was 14.5% [CI: 12.1%-17.1%]. Lesion ≥10mm was associated with greater recurrence (OR: 1.83 [CI: 1.13–2.96]; p=0.015), as was greater duration of follow-up (OR: 1.53 (CI: 1.17–2.01); p=0.002). No imaging modality was associated with significant differences in recurrence. Despite significant improvements in detection rates over four decades, there were no significant changes in the reported remission or recurrence rates. Conclusion: A lack of controlled comparative studies makes it difficult to draw definitive conclusions. Within this limitation, the results suggest that despite improvements in radiological detection rates of Cushing’s disease over the last four decades, there were no changes in clinical outcomes. Advances in imaging alone may be insufficient to improve surgical outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42020187751

Automated operative workflow analysis of endoscopic pituitary surgery using machine learning: development and preclinical evaluation (IDEAL stage 0)

OBJECTIVE: Surgical workflow analysis involves systematically breaking down operations into key phases and steps. Automatic analysis of this workflow has potential uses for surgical training, preoperative planning, and outcome prediction. Recent advances in machine learning (ML) and computer vision have allowed accurate automated workflow analysis of operative videos. In this Idea, Development, Exploration, Assessment, Long-term study (IDEAL) stage 0 study, the authors sought to use Touch Surgery for the development and validation of an ML-powered analysis of phases and steps in the endoscopic transsphenoidal approach (eTSA) for pituitary adenoma resection, a first for neurosurgery. METHODS: The surgical phases and steps of 50 anonymized eTSA operative videos were labeled by expert surgeons. Forty videos were used to train a combined convolutional and recurrent neural network model by Touch Surgery. Ten videos were used for model evaluation (accuracy, F1 score), comparing the phase and step recognition of surgeons to the automatic detection of the ML model. RESULTS: The longest phase was the sellar phase (median 28 minutes), followed by the nasal phase (median 22 minutes) and the closure phase (median 14 minutes). The longest steps were step 5 (tumor identification and excision, median 17 minutes); step 3 (posterior septectomy and removal of sphenoid septations, median 14 minutes); and step 4 (anterior sellar wall removal, median 10 minutes). There were substantial variations within the recorded procedures in terms of video appearances, step duration, and step order, with only 50% of videos containing all 7 steps performed sequentially in numerical order. Despite this, the model was able to output accurate recognition of surgical phases (91% accuracy, 90% F1 score) and steps (76% accuracy, 75% F1 score). CONCLUSIONS: In this IDEAL stage 0 study, ML techniques have been developed to automatically analyze operative videos of eTSA pituitary surgery. This technology has previously been shown to be acceptable to neurosurgical teams and patients. ML-based surgical workflow analysis has numerous potential uses-such as education (e.g., automatic indexing of contemporary operative videos for teaching), improved operative efficiency (e.g., orchestrating the entire surgical team to a common workflow), and improved patient outcomes (e.g., comparison of surgical techniques or early detection of adverse events). Future directions include the real-time integration of Touch Surgery into the live operative environment as an IDEAL stage 1 (first-in-human) study, and further development of underpinning ML models using larger data sets

Large-Eddy Simulation of Flow and Pollutant Transport in Urban Street Canyons with Ground Heating

Our study employed large-eddy simulation (LES) based on a one-equation subgrid-scale model to investigate the flow field and pollutant dispersion characteristics inside urban street canyons. Unstable thermal stratification was produced by heating the ground of the street canyon. Using the Boussinesq approximation, thermal buoyancy forces were taken into account in both the Navier–Stokes equations and the transport equation for subgrid-scale turbulent kinetic energy (TKE). The LESs were validated against experimental data obtained in wind-tunnel studies before the model was applied to study the detailed turbulence, temperature, and pollutant dispersion characteristics in the street canyon of aspect ratio 1. The effects of different Richardson numbers (Ri) were investigated. The ground heating significantly enhanced mean flow, turbulence, and pollutant flux inside the street canyon, but weakened the shear at the roof level. The mean flow was observed to be no longer isolated from the free stream and fresh air could be entrained into the street canyon at the roof-level leeward corner. Weighed against higher temperature, the ground heating facilitated pollutant removal from the street canyon.Singapore-MIT Alliance for Research and Technology. Center for Environmental Sensing and Monitorin

Sphingosine 1-phosphate receptor 4 promotes nonalcoholic steatohepatitis by activating NLRP3 inflammasome

BACKGROUND & AIMS: Sphingosine 1-phosphate receptors (S1PRs) are a group of G-protein-coupled receptors that confer a broad range of functional effects in chronic inflammatory and metabolic diseases. S1PRs also may mediate the development of nonalcoholic steatohepatitis (NASH), but the specific subtypes involved and the mechanism of action are unclear. METHODS: We investigated which type of S1PR isoforms is activated in various murine models of NASH. The mechanism of action of S1PR4 was examined in hepatic macrophages isolated from high-fat, high-cholesterol diet (HFHCD)-fed mice. We developed a selective S1PR4 functional antagonist by screening the fingolimod (2-amino-2-[2-(4- n-octylphenyl)ethyl]-1,3-propanediol hydrochloride)-like sphingolipid-focused library. RESULTS: The livers of various mouse models of NASH as well as hepatic macrophages showed high expression of S1pr4. Moreover, in a cohort of NASH patients, expression of S1PR4 was 6-fold higher than those of healthy controls. S1pr4(++/-) mice were protected from HFHCD-induced NASH and hepatic fibrosis without changes in steatosis. S1pr4 depletion in hepatic macrophages inhibited lipopolysaccharide-mediated Ca++ release and deactivated the Nod-like receptor pyrin domaincontainning protein 3 (NLRP3) inflammasome. S1P increased the expression of S1pr4 in hepatic macrophages and activated NLRP3 inflammasome through inositol trisphosphate/inositol trisphosphate-receptor-dependent [Ca++] signaling. To further clarify the biological function of S1PR4, we developed SLB736, a novel selective functional antagonist of SIPR4. Similar to S1pr4(+/-) mice, administration of SLB736 to HFHCD-fed mice prevented the development of NASH and hepatic fibrosis, but not steatosis, by deactivating the NLRP3 inflammasome. CONCLUSIONS: S1PR4 may be a new therapeutic target for NASH that mediates the activation of NLRP3 inflammasome in hepatic macrophages

Martial arts as a mental health intervention for children? Evidence from the ECLS-K

<p>Abstract</p> <p>Background</p> <p>Martial arts studios for children market their services as providing mental health outcomes such as self-esteem, self-confidence, concentration, and self-discipline. It appears that many parents enroll their children in martial arts in hopes of obtaining such outcomes. The current study used the data from the Early Childhood Longitudinal Study, Kindergarten class of 1998-1999, to assess the effects of martial arts upon such outcomes as rated by classroom teachers.</p> <p>Methods</p> <p>The Early Childhood Longitudinal Study used a multistage probability sampling design to gather a sample representative of U.S. children attending kindergarten beginning 1998. We made use of data collected in the kindergarten, 3^rdgrade, and 5^thgrade years. Classroom behavior was measured by a rating scale completed by teachers; participation in martial arts was assessed as part of a parent interview. The four possible combinations of participation and nonparticipation in martial arts at time 1 and time 2 for each analysis were coded into three dichotomous variables; the set of three variables constituted the measure of participation studied through regression. Multiple regression was used to estimate the association between martial arts participation and change in classroom behavior from one measurement occasion to the next. The change from kindergarten to third grade was studied as a function of martial arts participation, and the analysis was replicated studying behavior change from third grade to fifth grade. Cohen's f²effect sizes were derived from these regressions.</p> <p>Results</p> <p>The martial arts variable failed to show a statistically significant effect on behavior, in either of the regression analyses; in fact, the f²effect size for martial arts was 0.000 for both analyses. The 95% confidence intervals for regression coefficients for martial arts variables have upper and lower bounds that are all close to zero. The analyses not only fail to reject the null hypothesis, but also render unlikely a population effect size that differs greatly from zero.</p> <p>Conclusion</p> <p>The data from the ECLS-K fail to support enrolling children in martial arts to improve mental health outcomes as measured by classroom teachers.</p