To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Cutaneous leishmaniasis (CL) is a major health problem in many countries and its current treatment involves multiple parenteral injections with toxic drugs and requires intensive health services. Previously, the efficacy of a single subcutaneous injection with a slow-release formulation consisting of poly(lactide-co-glycolide) (PLGA) microparticles loaded with an antileishmanial 3-nitro-2-hydroxy-4,6-dimethoxychalcone (CH8) was demonstrated in mice model. In the search for more easily synthesized active chalcone derivatives, and improved microparticle loading, CH8 analogues were synthesized and tested for antileishmanial activity in vitro and in vivo. The 3-nitro-2′,4′,6′-trimethoxychalcone (NAT22) analogue was chosen for its higher selectivity against intracellular amastigotes (selectivity index = 1489, as compared with 317 for CH8) and more efficient synthesis (89% yield, as compared with 18% for CH8). NAT22 was loaded into PLGA / polyvinylpyrrolidone (PVP) polymeric blend microspheres (NAT22-PLGAk) with average diameter of 1.9 μm. Although NAT22-PLGAk showed similar activity to free NAT22 in killing intracellular parasites in vitro (IC50 ~ 0.2 μm), in vivo studies in Leishmania amazonensis – infected mice demonstrated the significant superior efficacy of NAT22-PLGAk to reduce the parasite load. A single intralesional injection with NAT22-PLGAk was more effective than eight injections with free NAT22. Together, these results show that NAT22-PLGAk is a promising alternative for single-dose localized treatment of CL.
Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.
To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.
The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.
In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO.
This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.
New oral treatments are needed for all forms of leishmaniasis. Here, the improved oral efficacy of quercetin (Qc) and its penta-acetylated derivative (PQc) was evaluated in cutaneous leishmaniasis after encapsulation in lipid-core nanocapsules (LNCs) of poly(ε-caprolactone). Leishmania amazonensis-infected BALB/c mice were given 51 daily oral doses of free drugs (16 mg kg−1) or LNC-loaded drugs (0·4 mg kg−1). While treatment with free Qc reduced the lesion sizes and parasite loads by 38 and 71%, respectively, LNC-Qc produced 64 and 91% reduction, respectively. The antileishmanial efficacy of PQc was similar but not as potently improved by encapsulation as Qc. None of the treatments increased aspartate aminotransferase, alanine aminotransferase or creatinine serum levels. These findings indicate that when encapsulated in LNC, Qc and, to a lesser extent, PQc can safely produce an enhanced antileishmanial effect even at a 40-fold lower dose, with implications for the development of a new oral drug for cutaneous leishmaniasis.
Leishmania amazonensis promastigotes are known to express furosemide (Lasix®)-sensitive P-type membrane Na+-ATPase. In the present study, furosemide activity was studied in intracellular amastigotes and infected BALB/c mice to investigate its efficacy in cutaneous leishmaniasis (CL). Intracellular parasites, but not macrophages, were found to be sensitive to killing by furosemide (IC50 = 87 µmvs CC50 ≫ 1000 µm, respectively). Although furosemide did not induce nitric oxide production or intracellular pH changes in infected macrophages, it led to a significant reactive oxygen species (ROS) burst. Freshly isolated tissue parasites expressed a high degree of Na+-ATPase activity that decreased with culture, indicative of a higher enzyme expression in amastigotes than in promastigotes. Both intraperitoneal and oral treatment of L. amazonensis-infected mice with furosemide dosages equivalent to that prescribed as a diuretic significantly reduced the parasite's growth compared with the situation in untreated mice. Combination with oral furosemide increased the efficacy and safety of intraperitoneal treatment with sodium stibogluconate (SSG). To summarize, furosemide control of intracellular leishmanial growth by means of parasite Na+-ATPase inhibition, and macrophage ROS activation may help explain its sole and SSG-combined therapeutic effect against murine CL.
The cubic polytype of silicon carbide is a stimulating candidate for Micro-Electro-Mechanical-Systems (MEMS) applications due to its interesting physical and chemical properties. Recently, we demonstrated the possibility to elaborate 3C-SiC membranes on 3C-SiC pseudo-substrates, using a silicon epilayer grown by Low Pressure Chemical Vapor Deposition as a sacrificial layer. Such structures could be the starting point for the elaboration of new MEMS devices. However, the roughness still represents a major concern. Therefore, in this contribution, we investigate the influence of an excimer laser irradiation on the Si epilayer surface prior to the 3C-SiC epilayer growth. We compare these results with the 3C-SiC epilayer grown directly on the as-grown Si epilayer.
Laser and oven annealing effects on hydrogen concentration, hydrogen diffusion and material microstructure in hydrogenated amorphous silicon films deposited on crystalline silicon substrates are compared. For laser annealing, a 6 W green (532 nm) continuous wave laser with 100 µm focus diameter was applied and samples of about 1 cm2 were scanned in ambient with a line distance of 50 µm and at a speed of 1 – 100 mm/s. Hydrogen content and microstructure were measured by infrared spectroscopy, and hydrogen diffusion was investigated by secondary ion mass spectroscopy (SIMS) measurements of depth profiles of deuterium and hydrogen in layered structures of deuterated and hydrogenated material. The results show that in both annealing experiments hydrogen diffuses predominantly in form of atoms although some formation of H2 molecules cannot be excluded. By comparison of laser and oven treatment, an effective temperature describing the laser treated state can be defined. Furthermore, the temperature of the thin silicon film during laser treatment is estimated.
This work is part of an ongoing project which aims to detect terrestrial planets in our neighbouring star system α Centauri using the Doppler method. Owing to the small angular separation between the two components of the α Cen AB binary system, the observations will to some extent be contaminated with light coming from the other star. We are accurately determining the amount of contamination for every observation by measuring the relative strengths of the H-α and NaD lines. Furthermore, we have developed a modified version of a well-established Doppler code that is modelling the observations using two stellar templates simultaneously. With this method we can significantly reduce the scatter of the radial velocity (RV) measurements due to spectral cross-contamination and hence increase our chances of detecting the tiny signature caused by potential Earth-mass planets. After correcting for the contamination we achieve RV precision of ~2.5 m s−1 for a given night of observations. We have also applied this new Doppler code to four southern double-lined spectroscopic binary systems (HR159, HR913, HR7578 and HD181958) and have successfully recovered radial velocities for both components simultaneously.
An accurate cartesian method is devised to simulate incompressible viscous flows past an arbitrary moving body. The Navier-Stokes equations are spatially discretized onto a fixed Cartesian mesh. The body is taken into account via the ghost-cell method and the so-called penalty method, resulting in second-order accuracy in velocity. The accuracy and the efficiency of the solver are tested through two-dimensional reference simulations. To show the versatility of this scheme we simulate a three-dimensional self propelled jellyfish prototype.
Fish consumption is the major dietary source of EPA and DHA, which according to rodent experiments may reduce body fat mass and prevent obesity. Only a few human studies have investigated the association between fish consumption and body-weight gain. We investigated the association between fish consumption and subsequent change in body weight. Women and men (n 344 757) participating in the European Prospective Investigation into Cancer and Nutrition were followed for a median of 5·0 years. Linear and logistic regression were used to investigate the associations between fish consumption and subsequent change in body weight. Among women, the annual weight change was 5·70 (95 % CI 4·35, 7·06), 2·23 (95 % CI 0·16, 4·31) and 11·12 (95 % CI 8·17, 14·08) g/10 g higher total, lean and fatty fish consumption per d, respectively. The OR of becoming overweight in 5 years among women who were normal weight at enrolment was 1·02 (95 % CI 1·01, 1·02), 1·01 (95 % CI 1·00, 1·02) and 1·02 (95 % CI 1·01, 1·04) g/10 g higher total, lean and fatty consumption per d, respectively. Among men, fish consumption was not statistically significantly associated with weight change. Adjustment for potential over- or underestimation of fish consumption did not systematically change the observed associations, but the 95 % CI became wider. The results in subgroups from analyses stratified by age or BMI at enrolment were not systematically different. In conclusion, the present study suggests that fish consumption has no appreciable association with body-weight gain.
Studies have suggested that moderate alcohol consumption is associated with a reduced risk of CVD and premature mortality in individuals with diabetes mellitus. However, history of alcohol consumption has hardly been taken into account. We investigated the association between current alcohol consumption and mortality in men and women with diabetes mellitus accounting for past alcohol consumption. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort was defined of 4797 participants with a confirmed diagnosis of diabetes mellitus. Men and women were assigned to categories of baseline and past alcohol consumption. Hazard ratios (HR) and 95 % CI for total mortality were estimated with multivariable Cox regression models, using light alcohol consumption (>0–6 g/d) as the reference category. Compared with light alcohol consumption, no relationship was observed between consumption of 6 g/d or more and total mortality. HR for >6–12 g/d was 0·89 (95 % CI 0·61, 1·30) in men and 0·86 (95 % CI 0·46, 1·60) in women. Adjustment for past alcohol consumption did not change the estimates substantially. In individuals who at baseline reported abstaining from alcohol, mortality rates were increased relative to light consumers: HR was 1·52 (95 % CI 0·99, 2·35) in men and 1·81 (95 % CI 1·04, 3·17) in women. The present study in diabetic individuals showed no association between current alcohol consumption >6 g/d and mortality risk compared with light consumption. The increased mortality risk among non-consumers appeared to be affected by their past alcohol consumption rather than their current abstinence.
We present preliminary results of a 4-month campaign carried out in the framework of the Mons project, where time-resolved Hα observations are used to study the wind and circumstellar properties of a number of OB stars.
We present the results from the spectroscopic follow-up of WR140 (WC7 + O4-5) during its last periastron passage in january 2009. This object is known as the archetype of colliding wind binaries and has a relatively large period (≃8 years) and eccentricity (≃0.89). We provide updated values for the orbital parameters, new estimates for the WR and O star masses and new constraints on the mass-loss rates.
A newly developed lectin neuraminidase test (LNT) and a panel of mouse monoclonal and post-infection ferret antibodies have been used to analyse antigenic drift in N1 neuraminidases of influenza A viruses isolated between 1933 and 1957 and also between 1977 and 1980. Significant antigenic differences were detected among the ‘early’ (1933–57) viruses since the NA of viruses isolated one year apart could be distinguished serologically. The NA ofthe ‘re-emerged’ virus A/USSR/92/77 (H1N1) was antigenically related but not identical to influenza A viruses isolated in 1949 (A/Paris/49 (H1N1), A/Geneva/49 (H1N1)) which thus predates the previously observed antigenic similarity of A/USSR/77 with A/FW/50 (H1N1) virus.
The goal of this work is to map the gas excitation and kinematics in the inner ~ 2 kiloparsecs of the radio-galaxy Arp 102B. Though being classified as an E0 galaxy, Arp 102B shows a nuclear gas spiral (Fathi et al., in preparation). Previous studies of the gas kinematics in nuclear spirals have led to the conclusion that these structures usually trace gas inflows (Fathi et al. 2006; [Storchi-Bergmann et al. 2007; [Riffel et al. 2008). We have used integral field spectroscopy obtained with GMOS instrument of the Gemini North telescope to investigate the nature of the nuclear spiral arms. The spectra cover the wavelength range 4400–7300 Å over a field of view of 5.″5 × 3.″9 (2.7 kpc × 1.9 kpc).
We analyze the grain size distribution during solid phase crystallization of Silicon thin films. We use a model developed recently that offers analytical expressions for the time-evolution of the grain size distribution during crystallization of a d-dimensional solid. Contrary to the usual fit of the experimental results with a lognormal distribution, the theory describes the data from basic physical principles such as nucleation and growth processes. The theory allows for a good description of the grain size distribution except for early stages of crystallization. The latter case is expected and discussed. An important outcome of the model is that the distribution at full crystallization is determined by the time-dependence of the nucleation and growth rates of grains. In the case under consideration, the theory leads to an analytical expression that has the form of a lognormal-type distribution for the fully crystallized sample.
Field trapping trials showed that Cameraria gaultheriella Walsingham and C. lobatiella Opler and Davis (Lepidoptera: Gracillariidae) were attracted in significant numbers in British Columbia, Canada, to sticky traps baited with 10 µg of (E,Z)-8,10-tetradecadienal (E8Z10-14Ald), the sex pheromone of the European horse chestnut leafminer, C. ohridella Deschka and Dimic. There was perfect specificity in captures at habitats located only about 8 km apart from each other: C. gaultheriella was captured exclusively at a humid habitat covered by the shrub salal, Gaultheria shallon Pursh (Ericaceae), whereas C. lobatiella was trapped at an arid location with Garry oak trees, Quercus garryana Dougl. (Fagaceae). Seasonal flight patterns of these two Canadian Cameraria species, as monitored by pheromone traps, indicated differences in their respective flight periods. The possibility of additional cryptic components in the respective pheromones of these three Cameraria species attracted to E8Z10-14Ald is discussed.