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► Study of mechanical and thermal properties of graphene nanoplatelets/epoxy composites. ► Processing by high pressure homogenizer and three roll mill to achieve uniform dispersion. ► ...Fracture toughness increased up to 66% over neat epoxy with EGNP reinforcement. ► Nanoindentation showed steady increase in hardness and modulus of composites. ► Significant improvement in thermal conductivity with incorporation of EGNPs.
Influence of reinforcements on mechanical and thermal properties of graphene nanoplatelets/epoxy composites is investigated. Amine functionalized expanded graphene nanoplatelets (EGNPs) were dispersed within epoxy resins using high-pressure processor followed by three roll milling. Functionality on the EGNPs was confirmed with FTIR and micro-Raman spectroscopy. Bending and nano-mechanical testing was performed on the composites. Incorporation of EGNPs improved the flexural modulus and hardness of the composite and increased fracture toughness by up to 60%. Marked improvement was observed in thermal conductivity of the composites reaching 36% at 2wt.% loading. Functionalized EGNPs exhibited significant improvements indicating favorable interaction at EGNPs/polymer interface.
For inversions of the GPS radio occultation (RO) data in the neutral atmosphere, this study investigates an optimal transition height for replacing the standard ionospheric correction using the ...linear combination of the L1 and L2 bending angles with the correction of the L1 bending angle by the L1–L2 bending angle extrapolated from above. The optimal transition height depends on the RO mission (i.e., the receiver and firmware) and is different between rising and setting occultations and between L2P and L2C GPS signals. This height is within the range of approximately 10–20 km. One fixed transition height, which can be used for the processing of currently available GPS RO data, can be set to 20 km. Analysis of the L1CA and the L2C bending angles shows that in some occultations the errors of standard ionospheric correction substantially increase around the strong inversion layers (such as the top of the boundary layer). This error increase is modeled and explained by the horizontal inhomogeneity of the ionosphere.
The dupilumab regimen of 300 mg every 2 weeks is approved for uncontrolled, moderate to severe atopic dermatitis (AD).
To assess the efficacy and safety of different dupilumab regimens in maintaining ...response after 16 weeks of initial treatment.
The Study to Confirm the Efficacy and Safety of Different Dupilumab Dose Regimens in Adults With Atopic Dermatitis (LIBERTY AD SOLO-CONTINUE) was a randomized, double-blind, phase 3 clinical trial conducted from March 25, 2015, to October 18, 2016, at 185 sites in North America, Europe, Asia, and Japan. Patients with moderate to severe AD who received dupilumab treatment and achieved an Investigator's Global Assessment score of 0 or 1 or 75% improvement in Eczema Area and Severity Index scores (EASI-75) at week 16 in 2 previous dupilumab monotherapy trials (LIBERTY AD SOLO 1 and 2) were rerandomized in SOLO-CONTINUE. After completing SOLO-CONTINUE, patients were followed up for up to 12 weeks or enrolled in an open-label extension. Data were analyzed from December 5 to 12, 2016.
High-responding patients treated with dupilumab in SOLO were rerandomized 2:1:1:1 to continue their original regimen of dupilumab, 300 mg, weekly or every 2 weeks or to receive dupilumab, 300 mg, every 4 or 8 weeks or placebo for 36 weeks.
Percentage change in EASI score from baseline during the SOLO-CONTINUE trial, percentage of patients with EASI-75 at week 36, and safety.
Among the 422 patients (mean SD age, 38.2 14.5 years; 227 53.8% male), continuing dupilumab treatment once weekly or every 2 weeks maintained optimal efficacy, with negligible change in percent EASI improvement from SOLO 1 and 2 baseline during the SOLO-CONTINUE trial (-0.06%; P < .001 vs placebo); percent change with the other regimens dose-dependently worsened (dupilumab every 4 weeks, -3.84%; dupilumab every 8 weeks, -6.84%; placebo, -21.67%). More patients taking dupilumab weekly or every 2 weeks (116 of 162 71.6%; P < .001 vs placebo) maintained EASI-75 response than those taking dupilumab every 4 weeks (49 of 84 58.3%) or every 8 weeks (45 of 82 54.9%) or those taking placebo (24 of 79 30.4%). Overall adverse event incidences were 70.7% in the weekly or every 2 weeks group, 73.6% in the every 4 weeks group, 75.0% in the every 8 weeks group, and 81.7% in the placebo group. Treatment groups had similar conjunctivitis rates. Treatment-emergent antidrug antibody incidence was lower with more frequent dupilumab dose regimens (11.3% in the placebo group and 11.7%, 6.0%, 4.3%, and 1.2% in the dupilumab every 8 weeks, every 4 weeks, every 2 weeks, and weekly groups, respectively).
In this trial, continued response over time was most consistently maintained with dupilumab administered weekly or every 2 weeks. Longer dosage intervals and placebo resulted in a diminution of response for both continuous and categorical end points. No new safety signals were observed. The approved regimen of 300 mg of dupilumab every 2 weeks is recommended for long-term treatment.
ClinicalTrials.gov identifier: NCT02395133.
Universal brain signature of proficient reading Rueckl, Jay G.; Paz-Alonso, Pedro M.; Molfese, Peter J. ...
Proceedings of the National Academy of Sciences - PNAS,
12/2015, Volume:
112, Issue:
50
Journal Article
Peer reviewed
Open access
We propose and test a theoretical perspective in which a universal hallmark of successful literacy acquisition is the convergence of the speech and orthographic processing systems onto a common ...network of neural structures, regardless of how spoken words are represented orthographically in a writing system. During functional MRI, skilled adult readers of four distinct and highly contrasting languages, Spanish, English, Hebrew, and Chinese, performed an identical semantic categorization task to spoken and written words. Results from three complementary analytic approaches demonstrate limited language variation, with speech–print convergence emerging as a common brain signature of reading proficiency across the wide spectrum of selected languages, whether their writing system is alphabetic or logographic, whether it is opaque or transparent, and regardless of the phonological and morphological structure it represents.
Freeze-fixation and freeze-gelation methods are presented in this paper which can be used to prepare highly porous scaffolds without using the time and energy consuming freeze-drying process. The ...porous structure was generated during the freeze of a polymer solution, following which either the solvent was extracted by a non-solvent or the polymer was gelled under the freezing condition; thus, the porous structure would not be destructed during the subsequent drying stage. Compared with the freeze-drying method, the presented methods are time and energy-saving, with less residual solvent, and easier to be scaled up. Besides, the problem of formation of surface skin can be resolved and the limitation of using solvent with low boiling point can be lifted by the presented methods. With the freeze-extraction and freeze-gelation methods, porous PLLA, PLGA, chitosan and alginate scaffolds were successfully fabricated. In addition to the presentation of the morphologies of the fabricated scaffolds, preliminary data of cell culture on them are as well included in the present work.
Abstract Background Mammalian target of rapamycin inhibitors (mTORi) play an essential role as novel immunosuppressive agents in kidney transplantation (KT). Treatment cessation usually occurs after ...adverse effects occur. We investigated the risk factors associated with withdrawal of mTORi in KT recipients and evaluated the outcomes related to the withdrawal. Methods The study enrolled KT recipients being followed up in a medical center in southern Taiwan from January 1999 through December 2014. Results Risk factors associated with mTORi withdrawal were initial proteinuria level, higher initial serum creatinine level posttransplantation, and history of glomerulonephritis as the primary etiology of renal failure. mTORi withdrawal was associated with increased risk of graft failure (hazard ratio HR, 9.97 95% confidence interval (CI), 1.03–96.8; P = .047). Higher body mass index (HR, 11.2 95% CI, 1.63–76.6; P = .01) and tacrolimus usage (HR, 8.30 95% CI, 1.14–60.7; P = .037) were associated with increased risk of new-onset diabetes after transplantation in mTORi withdrawal groups. Conclusions Proteinuria, poor graft function, and primary glomerulonephritis were associated with cessation of mTORi treatment. Earlier identification of these risk factors may prevent further adverse events and optimize transplantation outcomes after mTORi conversion.
The adipocyte-derived secretory factor adiponectin promotes insulin sensitivity, decreases inflammation and promotes cell survival. No unifying mechanism has yet explained how adiponectin can exert ...such a variety of beneficial systemic effects. Here, we show that adiponectin potently stimulates a ceramidase activity associated with its two receptors, AdipoR1 and AdipoR2, and enhances ceramide catabolism and formation of its antiapoptotic metabolite--sphingosine-1-phosphate (S1P)--independently of AMP-dependent kinase (AMPK). Using models of inducible apoptosis in pancreatic beta cells and cardiomyocytes, we show that transgenic overproduction of adiponectin decreases caspase-8-mediated death, whereas genetic ablation of adiponectin enhances apoptosis in vivo through a sphingolipid-mediated pathway. Ceramidase activity is impaired in cells lacking both adiponectin receptor isoforms, leading to elevated ceramide levels and enhanced susceptibility to palmitate-induced cell death. Combined, our observations suggest a unifying mechanism of action for the beneficial systemic effects exerted by adiponectin, with sphingolipid metabolism as its core upstream signaling component.
The characteristics of atmospheric tides in the upper troposphere and lower stratosphere region are investigated using radio occultation (RO) measurements performed by the Formosa Satellite ...Mission‐3/Constellation Observing System for Meteorology, Ionosphere, and Climate (FORMOSAT‐3/COSMIC) satellite constellation and compared to tides observed in short‐term forecast model fields of European Centre for Medium‐Range Weather Forecasts (ECMWF) and National Centers for Environmental Prediction (NCEP). Spectral analysis of 2 years of monthly data (2007 to 2008) yields the migrating diurnal tide to be the largest spectral component. This diurnal tide shows similar temporal, latitudinal, and altitudinal characteristics in all data sets equatorward of 50°. Beyond 50°, COSMIC local time sampling is insufficient within 1 month, which prevents space‐time spectral analysis from isolating atmospheric waves. Diurnal tides of temperature are characterized by largest amplitudes in the tropics (0.8 K to 1.0 K at an altitude of 30 km). Amplitudes of diurnal tides analyzed in model data are more pronounced by ∼20%. An annual cycle of the amplitudes, characteristically linked to the movement of the intertropical convergence zone, is clearly revealed. Tropical diurnal phase features downward progression of waves fronts with a vertical wavelength of 20 km. Extratropical diurnal tides are most pronounced in the model data sets with amplitudes of up to 0.5 K at 30 km. In this analysis we also see the influence of high‐altitude initialization of RO data by background information in using data processed by two different centers (University Corporation for Atmospheric Research (UCAR) and Wegener Center (WEGC)). UCAR data, initialized by a climatology without tidal information, exhibit no appreciable extratropical diurnal tides, while WEGC data, initialized by ECMWF forecasts, show more pronounced ones. Overall the results underpin the utility of the local‐time resolving COSMIC RO constellation data for monitoring diurnal tide dynamics in the stratosphere. The agreement between observational and model data further confirms that the tidal dynamics is appropriately captured in the models, which is important for other (middle/upper) atmosphere models relying on ECMWF or NCEP dynamics.
The cerebellum is best known for its role in controlling motor behaviors. However, recent work supports the view that it also influences non-motor behaviors. The contribution of the cerebellum ...towards different brain functions is underscored by its involvement in a diverse and increasing number of neurological and neuropsychiatric conditions including ataxia, dystonia, essential tremor, Parkinson’s disease (PD), epilepsy, stroke, multiple sclerosis, autism spectrum disorders, dyslexia, attention deficit hyperactivity disorder (ADHD), and schizophrenia. Although there are no cures for these conditions, cerebellar stimulation is quickly gaining attention for symptomatic alleviation, as cerebellar circuitry has arisen as a promising target for invasive and non-invasive neuromodulation. This consensus paper brings together experts from the fields of neurophysiology, neurology, and neurosurgery to discuss recent efforts in using the cerebellum as a therapeutic intervention. We report on the most advanced techniques for manipulating cerebellar circuits in humans and animal models and define key hurdles and questions for moving forward.
Present‐day shortcomings in the representation of upper tropospheric ice clouds in general circulation models (GCMs) lead to errors in weather and climate forecasts as well as account for a source of ...uncertainty in climate change projections. An ongoing challenge in rectifying these shortcomings has been the availability of adequate, high‐quality, global observations targeting ice clouds and related precipitating hydrometeors. In addition, the inadequacy of the modeled physics and the often disjointed nature between model representation and the characteristics of the retrieved/observed values have hampered GCM development and validation efforts from making effective use of the measurements that have been available. Thus, even though parameterizations in GCMs accounting for cloud ice processes have, in some cases, become more sophisticated in recent years, this development has largely occurred independently of the global‐scale measurements. With the relatively recent addition of satellite‐derived products from Aura/Microwave Limb Sounder (MLS) and CloudSat, there are now considerably more resources with new and unique capabilities to evaluate GCMs. In this article, we illustrate the shortcomings evident in model representations of cloud ice through a comparison of the simulations assessed in the Intergovernmental Panel on Climate Change Fourth Assessment Report, briefly discuss the range of global observational resources that are available, and describe the essential components of the model parameterizations that characterize their “cloud” ice and related fields. Using this information as background, we (1) discuss some of the main considerations and cautions that must be taken into account in making model‐data comparisons related to cloud ice, (2) illustrate present progress and uncertainties in applying satellite cloud ice (namely from MLS and CloudSat) to model diagnosis, (3) show some indications of model improvements, and finally (4) discuss a number of remaining questions and suggestions for pathways forward.
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