Causal relationships between type 2 diabetes, glycemic traits and keratoconus

PurposeThe relationship between diabetes mellitus and keratoconus remains controversial. This study aimed to assess the potential causal relationships among type 2 diabetes, glycemic traits, and the risk of keratoconus.MethodsWe used a two-sample Mendelian randomization (MR) design based on genome-wide association summary statistics. Fasting glucose, proinsulin levels, adiponectin, hemoglobin A1c (HbA1c) and type 2 diabetes with and without body mass index (BMI) adjustment were used as exposures and keratoconus was used as the outcome. MR analysis was performed using the inverse-variance weighted method, MR-Egger regression method, weighted-mode method, weighted median method and the MR-pleiotropy residual sum and outlier test (PRESSO).ResultsResults showed that genetically predicted lower fasting glucose were significantly associated with a higher risk of keratoconus [IVW: odds ratio (OR) = 0.382; 95% confidence interval (CI) = 0.261–0.560; p = 8.162 × 10−7]. Genetically predicted lower proinsulin levels were potentially linked to a higher risk of keratoconus (IVW: OR = 0.739; 95% CI = 0.568–0.963; p = 0.025). In addition, genetically predicted type 2 diabetes negatively correlated with keratoconus (IVW: BMI-unadjusted: OR = 0.869; 95% CI = 0.775–0.974, p = 0.016; BMI-adjusted: OR = 0.880, 95% CI = 0.789–0.982, p = 0.022). These associations were further corroborated by the evidence from all sensitivity analyses.ConclusionThese findings provide genetic evidence that higher fasting glucose levels are associated with a lower risk of keratoconus. However, further studies are required to confirmed this hypothesis and to understand the mechanisms underlying this putative causative relationship

The influence of acoustic field induced by HRT on oscillation behavior of a single droplet

This paper presents an experimental and theoretical study on the effects of an acoustic field induced by Hartmann Resonance Tube (HRT) on droplet deformation behavior. The characteristics of the acoustic field generated by HRT are investigated. Results show that the acoustic frequency decreases with the increase of the resonator length, the sound pressure level (SPL) increases with the increase of nozzle pressure ratio (NPR), and it is also noted that increasing resonator length can cause SPL to decrease, which has rarely been reported in published literature. Further theoretical analysis reveals that the resonance frequency of a droplet has several modes, and when the acoustic frequency equals the droplet's frequency, heightened droplet responses are observed with the maximum amplitude of the shape oscillation. The experimental results for different resonator cavity lengths, nozzle pressure ratios and droplet diameters confirm the non-linear nature of this problem, and this conclusion is in good agreement with theoretical analysis. Measurements by high speed camera have shown that the introduction of an acoustic field can greatly enhance droplet oscillation, which means with the use of an ultrasonic atomizer based on HRT, the quality of atomization and combustion can be highly improved

Numerical investigation on shock train control and applications in a scramjet engine

Different factors which help to control the shock train in the scramjet isolator and combustor were analyzed via numerical investigations, and were applied to a whole scramjet engine in the working environment. A streamline traced Busemann inlet is proposed and simulated along with an isolator. During the combustor design, the influence of boundary layer thickness, slot bleeding, cavity and hydrogen injection position on the basic combustor performance with uniform inlet flow condition are investigated, and it was found that the boundary layer bleeding could prevent the shock train from moving upstream, and the cavity could further enhance the combustion efficiency. By arranging hydrogen injections at certain intervals, it could reduce the combustion back pressure. An improved basic model by integrating the aforementioned advantages is then numerically studied. The results have shown that the improved combustor model contained a section of shock train which can reduce the loads on the isolator. Another model with bleeding slots in the isolator is also found able to raise the maximum chemical equivalence ratio from 0.7 to 1, but unfortunately it comes with undesirable combustion efficiency decrease

Structural Basis for Specific Binding of Human MPP8 Chromodomain to Histone H3 Methylated at Lysine 9

. MPP8 binding to methylated H3K9 is suggested to recruit the H3K9 methyltransferases GLP and ESET, and DNA methyltransferase 3A to the promoter of the E-cadherin gene, mediating the E-cadherin gene silencing and promote tumor cell motility and invasion. MPP8 contains a chromodomain in its N-terminus, which is used to bind the methylated H3K9. HP1, a chromodomain containing protein that binds to methylated H3K9 as well. The structure also reveals that the human MPP8 chromodomain forms homodimer, which is mediated via an unexpected domain swapping interaction through two β strands from the two protomer subunits.Our findings reveal the molecular mechanism of selective binding of human MPP8 chromodomain to methylated histone H3K9. The observation of human MPP8 chromodomain in both solution and crystal lattice may provide clues to study MPP8-mediated gene regulation furthermore

Neutrino Physics with JUNO

The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purposeunderground liquid scintillator detector, was proposed with the determinationof the neutrino mass hierarchy as a primary physics goal. It is also capable ofobserving neutrinos from terrestrial and extra-terrestrial sources, includingsupernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos,atmospheric neutrinos, solar neutrinos, as well as exotic searches such asnucleon decays, dark matter, sterile neutrinos, etc. We present the physicsmotivations and the anticipated performance of the JUNO detector for variousproposed measurements. By detecting reactor antineutrinos from two power plantsat 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4sigma significance with six years of running. The measurement of antineutrinospectrum will also lead to the precise determination of three out of the sixoscillation parameters to an accuracy of better than 1\%. Neutrino burst from atypical core-collapse supernova at 10 kpc would lead to ~5000inverse-beta-decay events and ~2000 all-flavor neutrino-proton elasticscattering events in JUNO. Detection of DSNB would provide valuable informationon the cosmic star-formation rate and the average core-collapsed neutrinoenergy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400events per year, significantly improving the statistics of existing geoneutrinosamples. The JUNO detector is sensitive to several exotic searches, e.g. protondecay via the $p\to K^++\bar\nu$ decay channel. The JUNO detector will providea unique facility to address many outstanding crucial questions in particle andastrophysics. It holds the great potential for further advancing our quest tounderstanding the fundamental properties of neutrinos, one of the buildingblocks of our Universe

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

Construction and analysis of Es2 efficient supersaturated designs

In this paper, we construct supersaturated designs for large numbers of two-level factors and 10?n?22 runs by augmenting k-circulant designs [Liu, Y., Dean, A.M., 2004. k-circulant supersaturated designs. Technometrics 46, 32–43] with interaction columns or by deleting columns from k-circulant designs. Most of the designs presented have Es2 efficiencies above 0.90 and they extend the range of efficient supersaturated designs available in the literature.Difficulties encountered in the use of supersaturated designs in detecting active factors are addressed. We show that, when only one factor is active, the regression technique of forward selection is guaranteed to select the correct factor as active under the idealized conditions that non-active factors have negligible effects and the errors are small. Under similar conditions, we derive bounds on the maximum allowable correlation between the columns of the model matrix that guarantee the correct selection of the “most active” factor when two or more factors are non-negligible. Further, we obtain conditions for the correct selection of the two most active factors using subset selection in regression. A number of designs that satisfy these conditions are identified

The complete mitochondrial genome of Lumbricus rubellus (Oligochaeta, Lumbricidae) and its phylogenetic analysis

The complete mitochondrial genome of Lumbricus rubellus was analyzed by next-generation sequencing. The mitogenome was 15,464 bp in length, comprising 13 protein-coding genes (PCGs), 22 transfer RNAs, 2 ribosomal RNAs, and a non-coding region. The phylogenetic analysis of 13 PCGs within the class Oligochaeta suggested that L. rubellus was placed as sister to L. terrestris of the same genus. The results obtained here can contribute to the phylogenetic analysis of earthworms