An increasing number of genetic variants have been implicated in autism spectrum disorders (ASDs), and the functional study of such variants will be critical for the elucidation of autism ...pathophysiology. Here, we report a de novo balanced translocation disruption of TRPC6, a cation channel, in a non-syndromic autistic individual. Using multiple models, such as dental pulp cells, induced pluripotent stem cell (iPSC)-derived neuronal cells and mouse models, we demonstrate that TRPC6 reduction or haploinsufficiency leads to altered neuronal development, morphology and function. The observed neuronal phenotypes could then be rescued by TRPC6 complementation and by treatment with insulin-like growth factor-1 or hyperforin, a TRPC6-specific agonist, suggesting that ASD individuals with alterations in this pathway may benefit from these drugs. We also demonstrate that methyl CpG binding protein-2 (MeCP2) levels affect TRPC6 expression. Mutations in MeCP2 cause Rett syndrome, revealing common pathways among ASDs. Genetic sequencing of TRPC6 in 1041 ASD individuals and 2872 controls revealed significantly more nonsynonymous mutations in the ASD population, and identified loss-of-function mutations with incomplete penetrance in two patients. Taken together, these findings suggest that TRPC6 is a novel predisposing gene for ASD that may act in a multiple-hit model. This is the first study to use iPSC-derived human neurons to model non-syndromic ASD and illustrate the potential of modeling genetically complex sporadic diseases using such cells.
This paper deals with a deterministic inventory model for linear trend in demand under inflationary conditions with different rates of deterioration in two separate warehouses (owned and rented ...warehouses). The replenishment rate is infinite. The stock is transferred from the rented warehouse to owned warehouse in continuous release pattern and the associated transportation cost is taken into account. At owned warehouse, shortages, if any, are allowed and partially backlogged with a rate dependent on the duration of waiting time up to the arrival of the next lot. The corresponding problems have been formulated as nonlinear constrained optimisation problems for two different policies (inventory follows shortage (IFS) and shortage follows inventory (SFI)). Finally, the model has been illustrated with a numerical example and to study the effects of changes of different system parameters on initial stock level, maximum shortage level and cycle length with the minimum cost of the system, sensitivity analyses have been carried out by changing one parameter at a time and keeping the others at their original values.
In this report, we report a green, rapid and scalable synthetic route for the production of reduced graphene oxide (rGO) using an environment-friendly reducing agent (l-glutathione/L-Glu) to test its ...feasibility for CO & NO2 gas sensing. The structure, morphology, and thermal stability of as-synthesized rGO are investigated via Raman spectroscopy, Fourier infrared spectroscopy, X-ray diffraction, Field emission scanning electron microscope, and thermal gravimetric analysis. The L-Glu-rGO shows higher sp2 carbon hybridization (42at.%) than graphene oxide (GO) (29 at.%). The results indicate that L-Glu-rGO exhibits good relative response at 150 °C to both gases (10 ppm of NO2 and CO). Further, L-Glu-rGO shows a smaller response time (∼10.61 s for NO2 and ∼5.05 s for CO) than GO (∼16.64 s, ∼11.92 s to NO2 and CO respectively) at 150 °C, indicating the potential application of L-Glu-rGO for gas sensing.
•Reduced graphene oxide synthesized by using an organic reducing agent l-glutathione.•XPS shows high percentage (42%) of sp2 carbon in L-Glu-rGO.•GO reduced through green method used for gas sensing of CO and NO2 gases.•Lower response and recovery time observed for L-Glu-rGO as compared to that for GO for both gases.
In the context of high-energy physics, the use of Nb 3 Sn superconducting magnets as a cost-effective and reliable technology depends on improvements in the following areas: long development and ...manufacturing cycles, conductor degradation after thermal cycling, long training, as well as a demonstration in accelerator magnets with a beam aperture of the full potential of modern Nb 3 Sn conductors. In short, performance, robustness, and cost are the three issues to be addressed. The Magnet Development project (MagDev) of the Swiss Accelerator Research and Technology initiative (CHART) at the Paul Scherrer Institute (PSI) aims to contribute to the solutions to each of these issues, re-thinking the manufacturing and design process. In our program, every innovation is to be validated by means of a panoply of fast-turnaround tools: from non-powered and powered samples and coils, tested under background field, to low-field subscale magnets and high field short prototypes. This work presents one element in this panoply of R&D vehicles: a stress-managed Nb 3 Sn coil called BigBOX, impregnated with paraffin wax, and tested, through a collaboration with the Magnet Development Program of the United States (US-MDP), in the background field of Brookhaven National Laboratory (BNL)'s common coils dipole DCC17.
Solution of Riemann problem for dusty gas flow Gupta, R.K.; Nath, Triloki; Singh, L.P.
International journal of non-linear mechanics,
June 2016, 2016-06-00, 20160601, Letnik:
82
Journal Article
Recenzirano
A direct approach is used to solve the Riemann problem for a quasilinear hyperbolic system of equations governing the one dimensional unsteady planar flow of an isentropic, inviscid compressible ...fluid in the presence of dust particles. The elementary wave solutions of the Riemann problem, that is, shock waves, rarefaction waves and contact discontinuities are derived and their properties are discussed for a dusty gas. The generalised Riemann invariants are used to find the solution between rarefaction wave and the contact discontinuity and also inside rarefaction fan. Unlike the ordinary gasdynamic case, the solution inside the rarefaction waves in dusty gas cannot be obtained directly and explicitly; indeed, it requires an extra iteration procedure. Although the case of dusty gas is more complex than the ordinary gas dynamics case, all the parallel results for compressive waves remain identical. We also compare/contrast the nature of the solution in an ordinary gasdynamics and the dusty gas flow case.
•Approximate analytical solution to the Riemann problem in a dusty gas is derived.•The generalised Riemann invariants are used to find the solution in some cases.•The properties of solutions to the Riemann problem of dusty gas are discussed.•The results of dusty gas are compared with those of ordinary gasdynamics.
Purpose:
To report patient demographics, the clinical course, and visual outcomes across a case series of patients who experienced dexamethasone (DEX) intravitreal implant (Ozurdex, Allergan, Inc) ...migration into the anterior chamber (AC), with a focus on the corneal transplantation rate.
Methods:
In this retrospective cross-sectional study, a chart review of all cases was performed. For numerical responses, means and SDs were calculated. Percentages and absolute numbers were used to report the proportion of patients who experienced various outcomes of interest.
Results:
The study comprised 32 cases. All cases occurred in pseudophakic eyes; of those, 8 (25.0%) had posterior chamber intraocular lenses in the capsular bag with no known capsular or zonular issues. The mean duration from DEX implant injection to detection of migration was 19.4 ± 14.5 days. The DEX implant was explanted in 21 patients (65.6%) and repositioned in the vitreous cavity or subconjunctival space in 6 patients (18.8%). Twelve patients (37.5%) ultimately required corneal transplantation.
Conclusions:
To our knowledge, this is the largest case series of DEX intravitreal implant migration into the AC compiled to date. Cases of migration occurred in individuals with no known history of significant prior zonule disruption. This potential complication should be discussed with all patients undergoing DEX implant injection, which may aid in earlier presentation and improved visual outcomes.
The computation of ejector geometry for a given fluid is essential and plays a crucial role in creating an ejector profile and performance analysis. The current paper discusses the constant rate of ...momentum change (CRMC) approach using a real gas equation for ejector design. The numerical analysis is carried to validate the analytical geometry and the effect of operating parameters on the entrainment ratio. The variation in entrainment ratio for the different working fluids has also been studied on the geometry computed for water-vapour. It is observed that the entrainment ratio of the ejector significantly varies with the change in operating conditions and working fluids. The numerically predicted entrainment ratio is ~0.354 compared to the on-design entrainment ratio 0.4 for water vapor, while the predicted entrainment ratio for other working fluids is ~0.319, ~0.314, and ~0.36 for air, N2, and CO2, respectively.
This paper presents a 2-D temperature-dependent analytical drain current model, which is valid for six different device architectures (by slightly modifying the used parameters), i.e., dual material ...gate dielectric pocket silicon-on-void, dual material gate silicon-on-void, dual material gate silicon-on-insulator, dielectric pocket silicon-on-void, silicon-on-void, and silicon-on-insulator MOSFETs. The results thus obtained, i.e., drain current, transconductance, g m /I ds ratio, threshold voltage, subthreshold slope, and I on /I off ratio have been verified with the simulated results obtained using ATLAS 3-D device simulator for channel length down to 30 nm. The analytical model is also used to investigate the impact of temperature variation on the characteristics of N-MOS inverter based on different architectures. In addition, impact of process and parameters variation (i.e., variation in shallow extension depth (X e ), side pillar thickness (T st ), thickness of buried oxide layer (t 3 ) along with the variation in temperature) on the subthreshold performance of different devices has also been studied through exhaustive device simulation.
Despite significant biological effects, the clinical use of chrysin has been restricted because of its poor oral bioavailability.
The purpose of the present research was to investigate the targeting ...potential of Mannose decorated chrysin (5,7- dihydroxyflavone) loaded solid lipid nanocarrier (MC-SLNs) for gastric cancer.
The Chrysin loaded SLNs (C-SLNs) were developed, optimized, characterized and further mannosylated. The C-SLNs were developed with a high shear homogenizer, optimized with 32 full factorial designs and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD) and Scanning Electron Microscope (SEM) and evaluated for particle size/polydispersity index, zeta-potential, entrapment efficiency, % release and haemolytic toxicity. The ex-vivo cytotoxicity study was performed on gastric cancer (ACG) and normal cell lines.
DSC and XRD data predict the chrysin encapsulation in the lipid core and FTIR results confirm the mannosylation of C-SLNs. The optimized C-SLNs exhibited a narrow size distribution with a particle size of 285.65 nm. The % Entrapment Efficiency (%EE) and % controlled release were found to be 74.43% and 64.83%. Once C-SLNs were coated with mannose, profound change was observed in a dependent variable - an increase in the particle size of MC-SLNs (307.1 nm) was observed with 62.87% release and 70.8% entrapment efficiency. Further, the in vitro studies depicted MC- SLNs to be least hemolytic than pure chrysin and C-SLNs. MC-SLNs were most cytotoxic and were preferably taken up ACG tumor cells as evaluated against C-SLNs.
These data suggested that the MC-SLNs demonstrated better biocompatibility and targeting efficiency to treat gastric cancer.
While uncommon, CNS-IRIS developing after the initiation of HAART in the setting of HIV-related severe immunosuppression is characterized by an intense inflammatory reaction to dead or latent ...organisms or to self-antigens due to a heightened but dysregulated immune response. While this reaction can range from mild to fulminating, encompassing a very wide clinical spectrum, it is important to recognize because changes in medical management may be necessary to prevent neurologic decline and even death. Once contained, however, this inflammatory response can be associated with improved patient outcome as immune function is restored. Among the infectious organisms that are most commonly associated with CNS-IRIS are the JC virus and Cryptococcus organisms, which will be the subject of this review. CD8 cell infiltration in the leptomeninges, perivascular spaces, blood vessels, and even parenchyma seems to be the pathologic hallmark of CNS-IRIS. While recognition of CNS-IRIS may be difficult, the onset of new or progressive clinical symptoms, despite medical therapy and despite improved laboratory data, and the appearance on neuroimaging studies of contrast enhancement, interstitial edema, mass effect, and restricted diffusion in infections not typically characterized by these findings in the untreated HIV-infected patient should raise the strong suspicion for CNS-IRIS. While CNS-IRIS is a diagnosis of exclusion, the neuroradiologist can play a critical role in alerting the clinician to the possibility of this syndrome.
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