SPATIALLY RESOLVED SPECTROSCOPY OF THE EXOPLANET HR 8799 c

HR 8799 is a multi-planet system detected in direct imaging, with three companions known so far. Here, we present spatially resolved Very Large Telescope/NACO 3.88-4.10 µm spectroscopy of the middle planet, HR 8799 c, which has an estimated mass of ~10 M Jup, temperature of ~1100 K, and projected separation of 38 AU. The spectrum shows some differences in the continuum from existing theoretical models, particularly longwards of 4 µm, implying that detailed cloud structure or non-equilibrium conditions may play an important role in the physics of young exoplanetary atmospheres.

Molecular dynamics simulation of nanoindentation of Fe3b>C and tetrahedral Fe4b>C

Study of nanomechanical response of iron carbides is important because presence of iron carbides greatly influences the performance and longevity of steel components. This work contributes to the literature by exploring nanoindentation of nanocrystalline Fe3C and tetrahedral-Fe4C using molecular dynamics simulation. The chemical interactions of iron and carbon were described through an analytical bond order inter-atomic potential (ABOP) energy function. The indentations were performed at an indentation speed of 50 m/sec and a repeat trial was performed at 5 m/sec. Load-displacement (P-h) curve for both these carbides showed residual indentation depth and maximum indentation depth (hf/hmax) ratio to be higher than 0.7 i.e. a circumstance where Oliver and Pharr method was not appropriate to be applied to evaluate the material properties. Alternate evaluation revealed Fe3C to be much harder than Fe4C. Gibbs free energy of formation and radial distribution function, coupled with state of the average local temperature and von Mises stresses indicate the formation of a new phase of iron-carbide. Formation of this newer phase was found to be due to deviatoric strain rather than the high temperature induced in the substrate during nanoindentation

Repeated measures of body mass index and C-reactive protein in relation to all-cause mortality and cardiovascular disease: Results from the consortium on health and ageing network of cohorts in Europe and the United States (CHANCES)

Obesity has been linked with elevated levels of C-reactive protein (CRP), and both have been associated with increased risk of mortality and cardiovascular disease (CVD). Previous studies have used a single ‘baseline’ measurement and such analyses cannot account for possible changes in these which may lead to a biased estimation of risk. Using four cohorts from CHANCES which had repeated measures in participants 50 years and older, multivariate time-dependent Cox proportional hazards was used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) to examine the relationship between body mass index (BMI) and CRP with all-cause mortality and CVD. Being overweight (≥25–<30 kg/m2) or moderately obese (≥30–<35) tended to be associated with a lower risk of mortality compared to normal (≥18.5–<25): ESTHER, HR (95 % CI) 0.69 (0.58–0.82) and 0.78 (0.63–0.97); Rotterdam, 0.86 (0.79–0.94) and 0.80 (0.72–0.89). A similar relationship was found, but only for overweight in Glostrup, HR (95 % CI) 0.88 (0.76–1.02); and moderately obese in Tromsø, HR (95 % CI) 0.79 (0.62–1.01). Associations were not evident between repeated measures of BMI and CVD. Conversely, increasing CRP concentrations, measured on more than one occasion, were associated with an increasing risk of mortality and CVD. Being overweight or moderately obese is associated with a lower risk of mortality, while CRP, independent of BMI, is positively associated with mortality and CVD risk. If inflammation links CRP and BMI, they may participate in distinct/independent pathways. Accounting for independent changes in risk factors over time may be crucial for unveiling their effects on mortality and disease morbidity.

Women, letter-writing and the life of the mind in England, c.1650-1750

Drawing on national and regional letter collections dating from the late seventeenth and early eighteenth centuries, this article explores women's experiences of the life of the mind through an analysis of their letter-writing. This study also highlights the shortcomings of the compartmentalised nature of scholarship on women's writing and intellectual lives and proposes the letter both as a beneficial historical source and methodological tool for research on women's mental worlds. By employing an inclusive definition of intellectual and creative life, and eschewing traditional benchmarks of achievement, this article contends that women took a full part in the cultures of knowledge of their time. 

Cystic Fibrosis from Laboratory to Bedside: The Role of A20 in NF-κB-Mediated Inflammation

Cystic fibrosis (CF) is a lifelong, inflammatory multi-organ disease and the most common lethal, genetic condition in Caucasian populations, with a median survival rate of 41.5 years. Pulmonary disease, characterized by infective exacerbations, bronchiectasis and increasing airway insufficiency is the most serious manifestation of this disease process, currently responsible for over 80% of CF deaths. Chronic dysregulation of the innate immune and host inflammatory response has been proposed as a mechanism central to this genetic condition, primarily driven by the nuclear factor κB (NF-κB) pathway. Chronic activation of this transcription factor complex leads to the production of pro-inflammatory cytokines and mediators such as IL-6, IL-8 and TNF-α. A20 has been described as a central and inducible negative regulator of NF-κB. This intracellular molecule negatively regulates NF-κB-driven pro-inflammatory signalling upon toll-like receptor activation at the level of TRAF6 activation. Silencing of A20 increases cellular levels of p65 and induces a pro-inflammatory state. We have previously shown that A20 expression positively correlates with lung function (FEV1%) in CF. Despite improvement in survival rates in recent years, advancements in available therapies have been incremental. We demonstrate that the experimental use of naturally occurring plant diterpenes such as gibberellin on lipopolysaccharide-stimulated cell lines reduces IL-8 release in an A20-dependent manner. We discuss how the use of a novel bio-informatics gene expression connectivity-mapping technique to identify small molecule compounds that similarly mimic the action of A20 may lead to the development of new therapeutic approaches capable of reducing chronic airway inflammation in CF. 

The effect of pantethine and ultraviolet-B radiation on the development of lenticular opacity in the emory mouse.

PURPOSE: Few studies have examined the impact of long-term treatments or exposures on the development of cataract in maturity-onset animal models. We studied the effect of treatment with D-pantethine and exposure to ultraviolet-B (UVB) radiation on the development of lenticular opacity in the Emory mouse. METHODS: A total of 164 Emory mice were randomized by litter at weaning to exposure to UVB light at 12 mJ/cm(2) for 6 hr/day (UV) or usual room light (A), and within litter, were further randomized to bi-weekly intra-peritoneal injections of 0.8 g/kg pantethine (T) or no treatment (C). Retro illumination lens photos were taken at 2, 4, 6, 8, and 10 months after weaning, and graded in masked fashion. The animals were sacrificed at 10 months and the lenses analyzed for total pantethine and total cysteamine. RESULTS: Lens pantethine and cysteamine levels were significantly (P < 0.001) higher for the T as compared to C litters. Mean cataract grade increased monotonically over time for all four groups. Unadjusted mean grade for the AT group at 8 (1.32) and 10 (1.86) months appeared lower than for the other groups (AC: 2.17, 2.39; UVC: 1.77, 2.40; UVT: 1.88, 2.37). However, the mean grade for the pantethine-treated litters did not differ significantly from the untreated litters except at 2 months (when untreated litters had significantly lower grades), when adjusting for UV treatment, gender and litter effect. No significant difference in cataract score existed between UV-exposed and ambient litters. Mortality was higher among pantethine-treated (hazard ratio = 1.8, p = 0.05) and UV-exposed animals (hazard ratio = 1.8, p = 0. 03) than among the untreated and unexposed litters. CONCLUSION: Significantly increased lens levels of pantethine are achieved with long-term intra-peritoneal dosing. The impact of pantethine on the progression of lenticular opacity in the Emory mouse is less than has been reported in other models. This level of chronic UVB exposure appeared to have no effect on the development of cataract in this model.

An R -matrix with pseudo-states calculation of electron-impact excitation in C 2 +

We have performed an R-matrix with pseudo-states (RMPS) calculation of electron-impact excitation in C2+.Collision strengths and effective collision strengths were determined for excitation between the lowest 24 terms, including all those arising from the 2s3l and 2s4l configurations. In the RMPS calculation, 238 terms (90 spectroscopic and 148 pseudo-state) were employed in the close-coupling (CC) expansion of the target. In order to investigate the significance of coupling to the target continuum and highly excited bound states, we compare the RMPS results with those from an R-matrix calculation that incorporated all 238 terms in the configuration- interaction expansion, but only the lowest 44 spectroscopic terms in the CC expansion. We also compare our effective collision strengths with those from an earlier 12-state R-matrix calculation (Berrington et al 1989 J. Phys. B: At.Mol. Opt. Phys. 22 665). The RMPS calculation was extremely large, involving (N +1)-electron Hamiltonian matrices of dimension up to 36 085, and required the use of our recently completed suite of parallel R-matrix programs. The full set of effective collision strengths fromourRMPS calculation is available at theOakRidgeNationalLaboratoryControlledFusion Atomic Data Center web site. 1.

Enhancement of the Cytotoxic Effect of Anticancer Agent by Cytochrome c Functionalised Hybrid Nanoparticles in Hepatocellular Cancer Cells

Treatment of hepatocellular cancer with chemotherapeutic agents has limited successin clinical practice and their efficient IC50 concentration would require extremely highdoses of drug administration which could not be tolerated due to systemic side effects.In order to potentiate the efficacy of anticancer agents we explored the potentialof co-treatment with pro-apoptotic Cytochrome c which activates the apoptoticpathway downstream of p53 that is frequently mutated in cancer. To this end weused hybrid iron oxide-gold nanoparticles as a drug delivery system to facilitate theinternalisation of Cytochrome c into cultured HepG2 hepatocellular carcinoma cells.Our results showed that Cytochrome c can be easily conjugated to the gold shell ofthe nanoparticles which are readily taken up by the cells. We used Cytochrome cin concentration (0.2μgmL-1) below the threshold required to induce apoptosis onits own. When the conjugate was administered to cells treated by doxorubicin, itsignificantly reduced its IC50 concentration from 9μgmL-1 to 3.5μgmL-1 as detectedby cell viability assay, and the efficiency of doxorubicin on decreasing viability ofHepG2 cells was significantly enhanced in the lower concentration range between0.01μgmL-1 to 5μgmL-1. The results demonstrate the potential of the application oftherapeutic proteins in activating the apoptotic pathway to complement conventionalchemotherapy to increase its efficacy. The application of hybrid iron oxide-goldnanoparticles can also augment the specificity of drug targeting and could serve as amodel drug delivery system for pro-apoptotic protein targeting and delivery.

Quantification of Type VI secretion system activity in macrophages infected with Burkholderia cenocepacia

The Gram-negative bacterial type VI Secretion System (T6SS) delivers toxins to kill orinhibit the growth of susceptible bacteria, while others target eukaryotic cells. Deletionof atsR, a negative regulator of virulence factors in B. cenocepacia K56-2, increasesT6SS activity. Macrophages infected with a K56-2 ΔatsR mutant display dramaticalterations in their actin cytoskeleton architecture that rely on the T6SS, which isresponsible for the inactivation of multiple Rho-family GTPases by an unknownmechanism. We employed a strategy to standardize the bacterial infection ofmacrophages and densitometrically quantify the T6SS-associated cellular phenotype,which allowed us to characterize the phenotype of systematic deletions of each genewithin the T6SS cluster and ten vgrG encoding genes in K56-2 ΔatsR. None of thegenes from the T6SS core cluster and the individual vgrGs were directly responsiblefor the cytoskeletal changes in infected cells. However, a mutant strain with all vgrGgenes deleted was unable to cause macrophage alterations. Despite not being able toidentify a specific effector protein responsible for the cytoskeletal defects inmacrophages, our strategy resulted in the identification of the critical core componentsand accessory proteins of the T6SS assembly machinery and provides a screeningmethod to detect T6SS effectors targeting the actin cytoskeleton in macrophages byrandom mutagenesis.