Measurements of immune responses for establishing correlates of vaccine protection against HIV

Well-defined correlates of protective immunity are an essential component of rational vaccine development. Despite years of basic science and three HIV vaccine efficacy trials, correlates of immunological protection from HIV infection remain undefined. In December 2010, a meeting of scientists engaged in basic and translational work toward developing HIV-1 vaccines was convened. The goal of this meeting was to discuss current opportunities and optimal approaches for defining correlates of protection, both for ongoing and future HIV-1 vaccine candidates; specific efforts were made to engage young scientists. We discuss here the highlights from the meeting regarding the progress made and the way forward for a protective HIV-1 vaccine.

On the use of OpenFOAM to model Oscillating wave surge converters

The Computational Fluid Dynamic (CFD) toolbox OpenFOAM is used to assess the applicability of Reynolds-Averaged Navier-Stokes (RANS) solvers to the simulation of Oscillating Wave Surge Converters (OWSC) in significant waves. Simulation of these flap type devices requires the solution of the equations of motion and the representation of the OWSC’s motion in a moving mesh. A new way to simulate the sea floor inside a section of the moving mesh with a moving dissipation zone is presented. To assess the accuracy of the new solver, experiments are conducted in regular and irregular wave traces for a full three dimensional model. Results of acceleration and flow features are presented for numerical and experimental data. It is found that the new numerical model reproduces experimental results within the bounds of experimental accuracy.

International inter-school competition to encourage children to walk to school: a mixed methods feasibility study.

Background: Active travel to school can be an important contributor to the total physical activity of children but levels have declined and more novel approaches are required to stimulate this as an habitual behaviour. The aim of this mixed methods study was to investigate the feasibility of an international walk to school competition supported by novel swipecard technology to increase children's walking to/from school. Methods: Children aged 9-13 years old participated in an international walk to school competition to win points for themselves, their school and their country over a 4-week period. Walks to and from school were recorded using swipecard technology and a bespoke website. For each point earned by participants, 1 pence (£0.01) was donated to the charity of the school's choice. The primary outcome was number of walks to/from school objectively recorded using the swipecard tracking system over the intervention period. Other measures included attitudes towards walking collected at baseline and week 4 (post-intervention). A qualitative sub-study involving focus groups with children, parents and teachers provided further insight. Results: A total of 3817 children (mean age 11.5±SD 0.7) from 12 schools in three cities (London and Reading, England and Vancouver, Canada) took part in the intervention, representing a 95% intervention participation rate. Results show a gradual decline in the average number of children walking to and from school over the 4-week period (week 1 mean 29%±SD2.5; week 2 mean 18%±SD3.6; week 3 mean 14%±SD4.0; week 4 mean 12%±SD1.1). Post intervention, 97% of children felt that walking to school helped them stay healthy, feel happy (81%) and stay alert in class (76%). These results are supported by qualitative findings from children, parents and teachers. Key areas for improvement include the need to incorporate strategies for maintenance of behaviour change into the intervention and also to adopt novel methods of data collection to increase follow-up rates. Conclusions: This mixed methods study suggests that an international walk to school competition using innovative technology can be feasibly implemented and offers a novel way of engaging schools and motivating children to walk to school.

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations.

METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.

RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)).

CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.

Chiral dienamides-substrates for asymmetric synthesis of amido cyclohexenes

Chiral dienamides, derived from chiral amines and oxazolidinones, react with electron deficient dienophiles Eo give amino-cyclohexanes with good to excellent de's.

CHROMIUM(II)-MEDIATED CONVERSION OF ALPHA,BETA-UNSATURATED ALDEHYDES TO CYCLOPROPANOLS

Chromium(II) chloride converts alpha,beta-unsaturated aldehydes to the corresponding cyclopropanols.

Inland shell midden site-formation:Investigation into a late Pleistocene to early Holocene midden from Trang An, Northern Vietnam

Over the course of the past two decades there has been growing research interest in the site formation processes of shell middens. This stands along-side and is being used to inform cultural, dietary and palaeo-environmental reconstructions. Just as midden site formation processes have turned out to be many and varied, however, the kinds of shell-bearing sites that past human communities created are likely to have been no less diverse. Subsuming such sites under a single category - shell middens - normalises that variation and may lead to the misinterpretation of site function. The greater part of research in this field also continues to focus on coastal shell middens; comparatively little attention has been paid to middens containing freshwater and especially terrestrial molluscs from hinterland locations. As a result, much of the current understanding about shell-midden sites carries a spatial as well as a functional bias. This paper hopes to contribute towards discussion on both fronts. It presents a detailed examination of the formation processes that went into the creation of a land snail-dominated late- to post-glacial midden from northern Vietnam, and considers the role that it may have played in the early settlement of this area. The data presented comes from ongoing archaeological excavations at Hang Boi, a cave located in the sub-coastal karstic uplands of Trang An park, in the Vietnamese Province of Ninh Binh. (C) 2010 Elsevier Ltd and INQUA. All rights reserved.

The 'human revolution' in lowland tropical Southeast Asia:the antiquity and behavior of anatomically modern humans at Niah Cave (Sarawak, Borneo)

Recent research in Europe, Africa, and Southeast Asia suggests that we can no longer assume a direct and exclusive link between anatomically modern humans and behavioral modernity (the 'human revolution'), and assume that the presence of either one implies the presence of the other: discussions of the emergence of cultural complexity have to proceed with greater scrutiny of the evidence on a site-by-site basis to establish secure associations between the archaeology present there and the hominins who created it. This paper presents one such case study: Niah Cave in Sarawak on the island of Borneo, famous for the discovery in 1958 in the West Mouth of the Great Cave of a modern human skull, the 'Deep Skull,' controversially associated with radiocarbon dates of ca. 40,000 years before the present. A new chronostratigraphy has been developed through a re-investigation of the lithostratigraphy left by the earlier excavations, AMS-dating using three different comparative pre-treatments including ABOX of charcoal, and U-series using the Diffusion-Absorption model applied to fragments of bones from the Deep Skull itself. Stratigraphic reasons for earlier uncertainties about the antiquity of the skull are examined, and it is shown not to be an `intrusive' artifact. It was probably excavated from fluvial-pond-desiccation deposits that accumulated episodically in a shallow basin immediately behind the cave entrance lip, in a climate that ranged from times of comparative aridity with complete desiccation, to episodes of greater surface wetness, changes attributed to regional climatic fluctuations. Vegetation outside the cave varied significantly over time, including wet lowland forest, montane forest, savannah, and grassland. The new dates and the lithostratigraphy relate the Deep Skull to evidence of episodes of human activity that range in date from ca. 46,000 to ca. 34,000 years ago. Initial investigations of sediment scorching, pollen, palynomorphs, phytoliths, plant macrofossils, and starch grains recovered from existing exposures, and of vertebrates from the current and the earlier excavations, suggest that human foraging during these times was marked by habitat-tailored hunting technologies, the collection and processing of toxic plants for consumption, and, perhaps, the use of fire at some forest-edges. The Niah evidence demonstrates the sophisticated nature of the subsistence behavior developed by modern humans to exploit the tropical environments that they encountered in Southeast Asia, including rainforest. (c) 2006 Elsevier Ltd. All rights reserved.

Prehistoric foragers and farmers in south-east Asia:Renewed investigations at Niah Cave, Sarawak

The paper describes the initial results from renewed investigations at Niah Cave in Sarawak on the island of Borneo, famous for the discovery in 1958 of the c. 40,000-year old 'Deep Skull'. The archaeological sequences from the West Mouth and the other entrances of the cave complex investigated by Tom and Barbara Harrisson and other researchers have potential implications for three major debates regarding the prehistory of south-east Asia: the timing of initial settlement by anatomically modern humans; the means by which they subsisted in the late Pleistocene and early Holocene; and the timing, nature, and causation of the transition from foraging to farming. The new project is informing on all three debates. The critical importance of the Niah stratigraphies was commonly identified - including by Tom Harrisson himself - as because the site provided a continuous sequence of occupation over the past 40,000 years. The present project indicates that Niah was first used at least 45,000 years ago, and probably earlier; that the subsequent Pleistocene and Holocene occupations were highly variable in intensity and character; and that in some periods, perhaps of significant duration, the caves may have been more or less abandoned. The cultural sequence that is emerging from the new investigations may be more typical of cave use in tropical rainforests in south-east Asia than the Harrisson model.