High-resolution x-ray study of the nematic - smectic-A and smectic-A - smectic-C transitions in 8barS5-aerosil gels

The effects of dispersed aerosil nanoparticles on two of the phase transitions of the thermotropic liquid crystal material 4-n-pentylphenylthiol-4'-n-octyloxybenzoate 8barS5 have been studied using high-resolution x-ray diffraction techniques. The aerosils hydrogen bond together to form a gel which imposes a weak quenched disorder on the liquid crystal. The smectic-A fluctuations are well characterized by a two-component line shape representing thermal and random-field contributions. An elaboration on this line shape is required to describe the fluctuations in the smectic-C phase; specifically the effect of the tilt on the wave-vector dependence of the thermal fluctuations must be explicitly taken into account. Both the magnitude and the temperature dependence of the smectic-C tilt order parameter are observed to be unaffected by the disorder. This may be a consequence of the large bare smectic correlation length in the direction of modulation for this transition. These results show that the understanding developed for the nematic to smectic-A transition for octylcyanobiphenyl (8CB) and octyloxycyanobiphenyl (8OCB) liquid crystals with quenched disorder can be extended to quite different materials and transitions.Comment: 7 pages, 8 figure

Environmental and Parental Influences on Offspring Health and Growth in Great Tits (Parus major)

PMCID: PMC3728352This 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

Inherited susceptibility to bleomycin-induced chromatid breaks in cultured peripheral blood lymphocytes

Background: Susceptibility to bleomycin-induced chromatid breaks in cultured peripheral blood lymphocytes may reflect the way a person deals with carcinogenic challenges. This susceptibility (also referred to as mutagen sensitivity) has been found to be increased in patients with environmentally related cancers, including cancers of the head and neck, lung, and colon, and, in combination with carcinogenic exposure, this susceptibility can greatly influence cancer risk. The purpose of this study was to assess the heritability of mutagen sensitivity. Methods: Heritability was determined by use of a maximum likelihood method that employed the FISHER package of pedigree analysis. Bleomycin-induced breaks per cell values for 135 healthy volunteers without cancer were determined. These individuals were from 53 different pedigrees and included 25 monozygotic twin pairs (n = 50), 14 pairs of dizygotes (twin pairs and siblings, n = 28), and 14 families selected on the basis of a first-degree relative who was successfully treated for head and neck cancer and who had no sign of recurrence for at least 1 year. All data were analyzed simultaneously, and different models of familial resemblance were fitted to the data. All P values are two-sided. Results: Our results showed no evidence for the influence of a shared family environment on bleomycin-induced chromatid breaks. Genetic influences, however, were statistically significant (P = .036) and accounted for 75% of the total variance. Conclusions: The high heritability estimate of the susceptibility to bleomycin-induced chromatid breaks indicates a clear genetic basis. The findings of this study support the notion that a common genetic susceptibility to DNA damage - and thereby a susceptibility to cancer - may exist in the general population

Experience and Challenges from Clinical Trials with Malaria Vaccines in Africa.

Malaria vaccines are considered amongst the most important modalities for potential elimination of malaria disease and transmission. Research and development in this field has been an area of intense effort by many groups over the last few decades. Despite this, there is currently no licensed malaria vaccine. Researchers, clinical trialists and vaccine developers have been working on many approached to make malaria vaccine available.African research institutions have developed and demonstrated a great capacity to undertake clinical trials in accordance to the International Conference on Harmonization-Good Clinical Practice (ICH-GCP) standards in the last decade; particularly in the field of malaria vaccines and anti-malarial drugs. This capacity is a result of networking among African scientists in collaboration with other partners; this has traversed both clinical trials and malaria control programmes as part of the Global Malaria Action Plan (GMAP). GMAP outlined and support global strategies toward the elimination and eradication of malaria in many areas, translating in reduction in public health burden, especially for African children. In the sub-Saharan region the capacity to undertake more clinical trials remains small in comparison to the actual need.However, sustainability of the already developed capacity is essential and crucial for the evaluation of different interventions and diagnostic tools/strategies for other diseases like TB, HIV, neglected tropical diseases and non-communicable diseases. There is urgent need for innovative mechanisms for the sustainability and expansion of the capacity in clinical trials in sub-Saharan Africa as the catalyst for health improvement and maintained

Identification of a new cocrystal of citric acid and paracetamol of pharmaceutical relevance

Cocrystals have been increasingly recognized as an attractive alternative delivery form for solid drug products. In this work, Raman spectroscopy, X-ray powder diffraction/X-ray crystallography, and differential scanning calorimetry have been used to study the phenomenon of cocrystal formation in stoichiometric mixtures of citric acid with paracetamol. Raman spectroscopy was particularly useful for the characterization of the products and was used to determine the nature of the interactions in the cocrystals. It was observed that little change in the vibrational modes associated with the phenyl groups of the respective reactants took place upon cocrystal formation but changes in intensities of the vibrational modes associated with the amide and the carboxylic acid groups were observed upon cocrystal formation. Several new vibrational bands were identified in the cocrystal which were not manifest in the raw material and could be used as diagnostic features of cocrystal formation. An understanding of the effects of cocrystal formation on the vibrational modes was obtained by the complete assignment of the spectra of the starting materials and of the cocrystal component. The results show that the cocrystals was obtained in a 2:1 molar ratio of paracetamol to citric acid. The asymmetric unit of the crystal contains two paracetamol molecules hydrogen-bonded to the citric acid; one of these acts as a phenolic-OH hydrogen bond donor to the carbonyl of a carboxylic acid arm of citric acid. In contrast, the other phenolic-OH acts as a hydrogen bond acceptor from the quaternary C-OH of citric acid. © 2011 The Royal Society of Chemistry

Framing the Paralympic Games: A Mixed-Methods Analysis of Spanish Media Coverage of the Beijing 2008 and London 2012 Paralympic Games

In recent years, there has been an increased emergence of studies focusing on the media coverage of the Paralympic Games. Until recently, studies have predominately used quantitative content analyses that, although providing useful interrogation of observational patterns, limits the understanding of and appreciation for the contexts that may have shaped the production of information. By focusing exclusively on the ‘what’ and on the ‘how much’ it is difficult to reveal the ‘why’ and to identify the underlying motives of any changes. This paper recognizes the nuances of the editorial decision-making process by using a mixed methods approach; employing quantitative and qualitative data drawn from a case study focusing on the Spanish media coverage of the 2008 and 2012 Paralympic Games. An initial content analysis of all news published in Spain’s twelve highest-circulation newspapers during Beijing 2008 and London 2012 Paralympic Games was undertaken. Subsequently, 15 semi-structured interviews were conducted with journalists that were also sent to these two iterations of the Paralympic Games by Spanish media. Drawing on conceptualisations of media framing, the results highlight that the numerical data alone shed insufficient light on the complexity of the news-making process. The semi-structured interviews brought to light issues such as editorial management buoyed by commercial imperatives, and organisational interjection in journalists’ narratives and authorship, that also contoured coverage and content. In addition to further debate about the complexities of media coverage of Paralympic sport, the study also underscores the utility of incorporating and combining qualitative and quantitative methodologies within sport media and communication research

Endocytic profiling of cancer cell models reveals critical factors influencing lipid nanoparticle mediated mRNA delivery and protein expression

Lipid nanoparticles have great potential for delivering nucleic acid-based therapeutics, but low efficiency limits their broad clinical translation. Differences in transfection capacity between in vitro models used for nanoparticle pre-clinical testing is poorly understood. To address this, using a clinically relevant lipid nanoparticle (LNP) delivering mRNA we highlight specific endosomal characteristics in in vitro tumour models that impact on protein expression. A 30-cell line LNP-mRNA transfection screen identified three cells lines having low, medium and high transfection that correlated with protein expression when they were analysed in tumour models. Endocytic profiling of these cell lines identified major differences in endolysosomal morphology, localisation, endocytic uptake, trafficking, recycling, and endolysosomal pH, identified using a novel pH probe. High transfecting cells showed rapid LNP uptake and trafficking through an organised endocytic pathway to lysosomes or rapid exocytosis. Low transfecting cells demonstrated slower endosomal LNP trafficking to lysosomes, and defective endocytic organisation and acidification. Our data establishes that efficient LNP-mRNA transfection relies on an early and narrow endosomal escape window prior to lysosomal sequestration and/or exocytosis. Endocytic profiling should form an important pre-clinical evaluation step for nucleic acid delivery systems to inform model selection and guide delivery system design for improved clinical translation

Evaluation of Oxfendazole, Praziquantel and Albendazole against Cystic Echinococcosis: A Randomized Clinical Trial in Naturally Infected Sheep

Cystic Echinococcosis (CE) is a near-cosmopolitan parasitic zoonosis that causes economic losses in many regions of the world. This parasitic infection can be regarded as an emerging or re-emerging disease causing considerable losses in livestock production. CE is produced by the larval cystic stage (hydatid) of the dog parasite Echinococcus granulosus. After infective eggs are ingested, cysts develop mainly in lungs and liver of humans and animals (sheep, cattle, pigs, horses, etc). Infected people may require surgery and/or Albendazole-based chemotherapy. In this study, we evaluated the effects of Oxfendazole alone (an antiparasitic drug used in animals), Oxfendazole plus Praziquantel, and Albendazole plus Praziquantel against hydatid cysts in sheep over 4 to 6 weeks of treatment. All of the treatments in this study were efficacious in killing the larval stages and, therefore, in minimizing the risk of a dog acquiring new infections (taenias). These treatment schemes can be added to control measures in animals and eventually could be used for the treatment of human infection. Further investigations on different schedules of monotherapy or combined chemotherapy are needed, as well as studies to evaluate the safety and efficacy of Oxfendazole in humans