The mechanical properties and toughening mechanisms of an epoxy polymer modified with polysiloxane-based core-shell particles

AbstractAn epoxy resin, cured using an anhydride hardener, has been modified by the addition of pre-formed polysiloxane core-shell rubber (S-CSR) particles with a mean diameter of 0.18 μm. The glass transition temperature, Tg, of the cured unmodified epoxy polymer was 148 °C, and this was unchanged after the addition of the S-CSR particles. The polysiloxane rubber particles had a Tg of about −100 °C. Atomic force microscopy showed that the S-CSR particles were well-dispersed in the epoxy polymer. The addition of the S-CSR particles reduced the Young's modulus and tensile strength of the epoxy polymer, but at 20 °C the fracture energy, GIc, increased from 117 J/m2 for the unmodified epoxy to 947 J/m2 when 20 wt% of the S-CSR particles were incorporated. Fracture tests were also performed at −55 °C, −80 °C, and −109 °C. The results showed that the measured fracture energy of the S-CSR-modified epoxy polymers decreased significantly below room temperature. For example, at −109 °C, a fracture energy of 481 J/m2 was measured using 20 wt% of S-CSR particles. Nevertheless, this value of toughness still represented a major increase compared with the unmodified epoxy polymer, which possessed a value of GIc of 174 J/m2 at this very low test temperature. Thus, a clear fact that emerged was that the addition to the epoxy polymer of the S-CSR particles may indeed lead to significant toughening of the epoxy, even at temperatures as low as about −100 °C. The toughening mechanisms induced by the S-CSR particles were identified as (a) localised plastic shear-band yielding around the particles and (b) cavitation of the particles followed by plastic void growth of the epoxy polymer. These mechanisms were modelled using the Hsieh et al. approach [33,49] and the values of GIc of the S-CSR-modified epoxy polymers at the different test temperatures were calculated. Excellent agreement was found between the predictions and the experimentally measured fracture energies. Further, the experimental and modelling results of the present study indicated that the extent of plastic void growth was suppressed at low temperatures for the S-CSR-modified epoxy polymers, but that the localised shear-band yielding mechanism was relatively insensitive to the test temperature

The comparison of immunomodulatory effects of peripheral mononuclear cells against proliferation in U937 in junior elderly habitual morning swimming in Taiwan cohort

The present investigation was carried out to evaluate the effect of greater immunomodulatory effects of human peripheral blood mononuclear cells against proliferation in human leukemia cells. To achieve this, cells U937 in junior elderly (with cool environmental physical activities) subjects with habitual morning swimming and sedentary lifestyle were recruited in relatively cool season in Taiwan; the isolated human peripheral blood mononuclear cells were stimulated by phytohemagglutinin to obtain the conditioned medium which contains various cytokines. However, the differential effects of the conditioned medium on growth inhibition in U937 leukemia cells were observed. The cytokines, including interferon-gamma, tumor necrosis factors-alpha and interleukine-2 secreted into conditioned medium were higher in the morning-swimming subjects than in the sedentary-lifestyle ones. Similarly, serum white blood cell, creatine phosphokinase, immunoglobulin G and immunoglobulin A in the morning-swimming and sedentary-lifestyle groups indicated that no further inflammatory status existed in the morning-swimming group. In summary, greater immunomodulatory effects of human peripheral blood mononuclear cells against proliferation in human leukemia cells U937 in junior elderly subjects came from the effects of regular moderate exercise in cool temperature rather than of inflammatory effects.Keywords: Immunomodulatory, junior elderly, morning swimming, leukemia, U937, human peripheral blood mononuclear cell

Novel PDE4 inhibitors derived from Chinese medicine Forsythia

Cyclic adenosine monophosphate (cAMP) is a crucial intracellular second messenger molecule that converts extracellular molecules to intracellular signal transduction pathways generating cell- and stimulus-specific effects. Importantly, specific phosphodiesterase (PDE) subtypes control the amplitude and duration of cAMP-induced physiological processes and are therefore a prominent pharmacological target currently used in a variety of fields. Here we tested the extracts from traditional Chinese medicine, Forsythia suspense seeds, which have been used for more than 2000 years to relieve respiratory symptoms. Using structural-functional analysis we found its major lignin, Forsynthin, acted as an immunosuppressant by inhibiting PDE4 in inflammatory and immune cell. Moreover, several novel, selective small molecule derivatives of Forsythin were tested in vitro and in murine models of viral and bacterial pneumonia, sepsis and cytokine-driven systemic inflammation. Thus, pharmacological targeting of PDE4 may be a promising strategy for immune-related disorders characterized by amplified host inflammatory response

Temporal reprogramming of calcium signalling via crosstalk of gonadotrophin receptors that associate as functionally asymmetric heteromers.

Signal crosstalk between distinct G protein-coupled receptors (GPCRs) is one mechanism that underlies pleiotropic signalling. Such crosstalk is also pertinent for GPCRs activated by gonadotrophic hormones; follicle-stimulating hormone (FSH) and luteinising hormone (LH), with specific relevance to female reproduction. Here, we demonstrate that gonadotrophin receptor crosstalk alters LH-induced Gαq/11-calcium profiles. LH-induced calcium signals in both heterologous and primary human granulosa cells were prolonged by FSHR coexpression via influx of extracellular calcium in a receptor specific manner. LHR/FSHR crosstalk involves Gαq/11 activation as a Gαq/11 inhibitor abolished calcium responses. Interestingly, the enhanced LH-mediated calcium signalling induced by FSHR co-expression was dependent on intracellular calcium store release and involved Gβγ. Biophysical analysis of receptor and Gαq interactions indicated that ligand-dependent association between LHR and Gαq was rearranged in the presence of FSHR, enabling FSHR to closely associate with Gαq following LHR activation. This suggests that crosstalk may occur via close associations as heteromers. Super-resolution imaging revealed that LHR and FSHR formed constitutive heteromers at the plasma membrane. Intriguingly, the ratio of LHR:FSHR in heterotetramers was specifically altered following LH treatment. We propose that functionally significant FSHR/LHR crosstalk reprograms LH-mediated calcium signalling at the interface of receptor-G protein via formation of asymmetric complexes

Exogenous WNT5A and WNT11 proteins rescue CITED2 dysfunction in mouse embryonic stem cells and zebrafish morphants

Mutations and inadequate methylation profiles of CITED2 are associated with human congenital heart disease (CHD). In mouse, Cited2 is necessary for embryogenesis, particularly for heart development, and its depletion in embryonic stem cells (ESC) impairs cardiac differentiation. We have now determined that Cited2 depletion in ESC affects the expression of transcription factors and cardiopoietic genes involved in early mesoderm and cardiac specification. Interestingly, the supplementation of the secretome prepared from ESC overexpressing CITED2, during the onset of differentiation, rescued the cardiogenic defects of Cited2-depleted ESC. In addition, we demonstrate that the proteins WNT5A and WNT11 held the potential for rescue. We also validated the zebrafish as a model to investigate cited2 function during development. Indeed, the microinjection of morpholinos targeting cited2 transcripts caused developmental defects recapitulating those of mice knockout models, including the increased propensity for cardiac defects and severe death rate. Importantly, the co-injection of anti-cited2 morpholinos with either CITED2 or WNT5A and WNT11 recombinant proteins corrected the developmental defects of Cited2-morphants. This study argues that defects caused by the dysfunction of Cited2 at early stages of development, including heart anomalies, may be remediable by supplementation of exogenous molecules, offering the opportunity to develop novel therapeutic strategies aiming to prevent CHD.Agência financiadora: Fundação para a Ciência e a Tecnologia (FCT) Comissão de Coordenação e Desenvolvimento Regional do Algarve (CCDR Algarve) ALG-01-0145-FEDER-28044; DFG 568/17-2 Algarve Biomedical Center (ABC) Municipio de Louléinfo:eu-repo/semantics/publishedVersio

Socio-demographic and health service factors associated with antibiotic dispensing in older Australian adults

© 2019 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Widespread use of antibiotics has led to the development of antibiotic resistance. However, there are limited data describing antibiotic use in the community setting, and examining factors associated with greater use. Our study aimed to quantify antibiotic dispensing in older adults in the community according to socio-demographics and health services use. Methods Prospective analysis of a population-based cohort study of 239,981 adults aged 45 years in Australia (the Sax Institute’s 45 and Up Study). Data on socio-demographics and health from a questionnaire, were linked to 2015 antibiotic dispensing data from the Pharmaceutical Benefits Scheme (PBS), as well as other administrative health databases. We estimated the Defined Daily Dose (DDD) of systemic antibiotics dispensed, defined by an Anatomic Therapeutic Classification code beginning with J01, in 2015. We also conducted Poisson regression with robust standard errors to identify factors associated with antibiotic dispensing. Results Overall, 49.3% of 45 and Up Study participants had at least one systemic antibiotic dispensed in 2015 with a total of 392,856 prescriptions dispensed and an average of 36.5 DDDs/1000-persons/day in the study population. The quantity of antibiotics dispensed increased with increasing age (25.6 DDDs/1000/day in 15 general practitioner consultations in the last year (80.5 and 88.3 DDDs/1000/day, respectively). These factors remained strongly associated with greater antibiotic dispensing after adjusting for age, sex, education, income, area of residence and co-morbidities. Conclusions Residence in aged care facilities and high GP visits are associated with greater antibiotic dispensing. This study provides important evidence regarding high use groups for antimicrobial stewardship

Sliding charge density wave in manganites

The so-called stripe phase of the manganites is an important example of the complex behaviour of metal oxides, and has long been interpreted as the localisation of charge at atomic sites. Here, we demonstrate via resistance measurements on La_{0.50}Ca_{0.50}MnO_3 that this state is in fact a prototypical charge density wave (CDW) which undergoes collective transport. Dramatic resistance hysteresis effects and broadband noise properties are observed, both of which are typical of sliding CDW systems. Moreover, the high levels of disorder typical of manganites result in behaviour similar to that of well-known disordered CDW materials. Our discovery that the manganite superstructure is a CDW shows that unusual transport and structural properties do not require exotic physics, but can emerge when a well-understood phase (the CDW) coexists with disorder.Comment: 13 pages; 4 figure

Intrinsic and Extrinsic Performance Limits of Graphene Devices on SiO2

The linear dispersion relation in graphene[1,2] gives rise to a surprising prediction: the resistivity due to isotropic scatterers (e.g. white-noise disorder[3] or phonons[4-8]) is independent of carrier density n. Here we show that acoustic phonon scattering[4-6] is indeed independent of n, and places an intrinsic limit on the resistivity in graphene of only 30 Ohm at room temperature (RT). At a technologically-relevant carrier density of 10^12 cm^-2, the mean free path for electron-acoustic phonon scattering is >2 microns, and the intrinsic mobility limit is 2x10^5 cm^2/Vs, exceeding the highest known inorganic semiconductor (InSb, ~7.7x10^4 cm^2/Vs[9]) and semiconducting carbon nanotubes (~1x10^5 cm^2/Vs[10]). We also show that extrinsic scattering by surface phonons of the SiO2 substrate[11,12] adds a strong temperature dependent resistivity above ~200 K[8], limiting the RT mobility to ~4x10^4 cm^2/Vs, pointing out the importance of substrate choice for graphene devices[13].Comment: 16 pages, 3 figure

Adaptive Evolutionary Clustering

In many practical applications of clustering, the objects to be clustered evolve over time, and a clustering result is desired at each time step. In such applications, evolutionary clustering typically outperforms traditional static clustering by producing clustering results that reflect long-term trends while being robust to short-term variations. Several evolutionary clustering algorithms have recently been proposed, often by adding a temporal smoothness penalty to the cost function of a static clustering method. In this paper, we introduce a different approach to evolutionary clustering by accurately tracking the time-varying proximities between objects followed by static clustering. We present an evolutionary clustering framework that adaptively estimates the optimal smoothing parameter using shrinkage estimation, a statistical approach that improves a naive estimate using additional information. The proposed framework can be used to extend a variety of static clustering algorithms, including hierarchical, k-means, and spectral clustering, into evolutionary clustering algorithms. Experiments on synthetic and real data sets indicate that the proposed framework outperforms static clustering and existing evolutionary clustering algorithms in many scenarios.Comment: To appear in Data Mining and Knowledge Discovery, MATLAB toolbox available at http://tbayes.eecs.umich.edu/xukevin/affec