Funding criteria for research, development, and exploration projects

The sequential nature of activities like research, development, or exploration requires optimal funding criteria to take account of the fact that subsequent funding decisions will be made throughout the future. Thus, there is a continual possibility of reviewing a project's status, based on the latest information. After setting up a model to capture this feature, optimal funding criteria are investigated. In an important special case, an explicit formula is derived. As well as throwing light upon the nature of development activities, the analysis is also relevant to the general theory of information gathering processes

Vitamin A and zinc supplementation among pregnant women to prevent placental malaria: a randomized, double-blind, placebo-controlled trial in Tanzania

BACKGROUND: Malaria causes nearly 200 million clinical cases and approximately half a million deaths each year, primarily in sub-Saharan Africa.1 The risk of malaria increases during pregnancy,2 a period during which its prevention is especially important. Not only do pregnant women experience greater severity of illness compared with nonpregnant women,2 but studies have shown strong associations between prenatal malaria and maternal anemia,2 fetal loss, low birthweight, and infant mortality.2 Improving preventive measures that specifically target malaria in pregnancy is a global health priority.3 METHODS: Study design and participants. This randomized, doubleblind, placebo-controlled trial was implemented at 8 antenatal care clinics in the urban Temeke and Ilala districts of Dar es Salaam, Tanzania. The trial was registered RESULTS: A total of 2,500 screened participants were enrolled in the trial. The trial profile is shown in Figure 1. It was not possible to collect placentas from 875 participants for the following reasons: miscarriages (fetal loss before 28 weeks of gestation) (N = 234), delivery outside of Dar es Salaam or at a non-study hospital (N = 577), or withdrawal from the study (N = 34). Of the remaining 1,589 women, 1,404 placental samples were obtained (88%); histology results were available for 1,361 participants. PCR results were available for 1,158 participants, and 1,404 participants had either histology or PCR results available. CONCLUSION: This study is the first to examine the impact of vitamin A and zinc supplementation starting in early pregnancy on placental malaria. We observed that supplementation with 25 mg zinc per day from the first trimester until delivery was associated with a 36% (95% CI = 9–56%) reduced risk of histopathology-positive placental infection, but not PCRpositive infection. Vitamin A supplementation had no impact on placental malaria, but was associated with an increased risk for severe anemia

A matched study of surgically treated stage IB adenosquamous carcinoma and adenocarcinoma of the uterine cervix

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72055/1/j.1525-1438.1993.03040245.x.pd

Design and performance of the PALM-3000 3.5 kHz upgrade

PALM-3000 (P3K), the second-generation adaptive optics (AO) instrument for the 5.1 meter Hale telescope at Palomar Observatory, underwent a significant upgrade to its wavefront sensor (WFS) arm and real-time control (RTC) system in late 2019. Main features of this upgrade include an EMCCD WFS camera capable of 3.5 kHz framerates and advanced Digital Signal Processor (DSP) boards to replace the aging GPU based real-time control system. With this upgrade P3K is able to maintain a lock on natural guide stars fainter than mV=16. Here we present the design and on-sky re-commissioning results of the upgraded system

Nonlinear landscape and cultural response to sea-level rise

Dataset S1 (separate file). Relative sea-level database for Scilly comprising directly dated radiocarbon and optically stimulated luminescence samples with corresponding metainformation (lithostratigraphy, elevation, depositional environment and indicative meaning interpretations, paleotidal range change and sea-level calculations) following the ‘HOLSEA’ (‘Geographic Variability of Holocene Relative Sea Level’) protocol (Khan et al., 2019*). Dataset S2 (separate file). Table containing pollen results as relative abundance (genus level), modelled ages and age uncertainty for pollen samples, landcover index results (community cluster numbers and nMDS ordination axes 1 and 2), foraminifera results as species counts and transfer function results as paleomarsh elevations with uncertainty (1σ). Foraminifera samples with low test concentrations have indicative ranges (from mean high water neap tides to highest astronomical tides) in place of paleomarsh elevation estimations. Foraminifera abbreviations: H.wil – Haplophragmoides wilbertii ; J.mac – Jadammina macrescens ; M.fus – Miliammina fusca ; P.ipo – Polysaccammina ipohalina ; T.inf – Trochammina infalta ; T.och – Trochammina ochracea ; A.bat - Ammonia batavus ; A.mam – Asterigerinata mamilla ; B.var – Bolivina variablis; E.cri – Elphidium crispum ; E.wil – Elphidium Williamsoni ; F.spp. – Fissurina spp. ; Elphidium spp. ; H.ger – Haynesina germanica ; L.lob – Lobatula lobatula ; O.spp. – Oolha spp. ; Q.sem – Quinqueloculina seminula; R.spp. – Rosalina spp.. Dataset S3 (separate file). Database containing three worksheets for developing archaeological indices for Scilly. ‘SWBritain’ – Radiocarbon dates from Devon and Cornwall used to develop a summed probability distribution curve as an estimate of population demographic variation in Southwest Britain. ‘NWFrance’ - Radiocarbon dates from Brittany and Normandy used to develop a summed probability distribution curve as an estimate of population demography in Northwest France. ‘Scilly’ – Archaeological monuments from Scilly used to develop a probabilistic index of population variability.The article associated with these datasets is located in ORE at: http://hdl.handle.net/10871/123489Rising sea levels have been associated with human migration and behavioral shifts throughout prehistory, often with an emphasis on landscape submergence and consequent societal collapse. However, the assumption that future sea-level rise will drive similar adaptive responses is overly simplistic. Whilst the change from land to sea represents a dramatic and permanent shift for pre-existing human populations, the process of change is driven by a complex set of physical and cultural processes with long transitional phases of landscape and socio-economic change. Here we use reconstructions of prehistoric sea-level rise, paleogeographies, terrestrial landscape change and human population dynamics to show how the gradual inundation of an island archipelago resulted in decidedly non-linear landscape and cultural responses to rising sea-levels. Interpretation of past and future responses to sea-level change requires a better understanding of local physical and societal contexts to assess plausible human response patterns in the future.Historic EnglandWelsh GovernmentHigher Education Funding Council for Wale

Search for gravitational waves associated with the InterPlanetary Network short gamma ray bursts

We outline the scientific motivation behind a search for gravitational waves associated with short gamma ray bursts detected by the InterPlanetary Network (IPN) during LIGO's fifth science run and Virgo's first science run. The IPN localisation of short gamma ray bursts is limited to extended error boxes of different shapes and sizes and a search on these error boxes poses a series of challenges for data analysis. We will discuss these challenges and outline the methods to optimise the search over these error boxes.Comment: Methods paper; Proceedings for Eduardo Amaldi 9 Conference on Gravitational Waves, July 2011, Cardiff, U

Recombinant plants provide a new approach to the production of bacterial polysaccharide for vaccines

Bacterial polysaccharides have numerous clinical or industrial uses. Recombinant plants could offer the possibility of producing bacterial polysaccharides on a large scale and free of contaminating bacterial toxins and antigens. We investigated the feasibility of this proposal by cloning and expressing the gene for the type 3 synthase (cps3S) of Streptococcus pneumoniae in Nicotinia tabacum, using the pCambia2301 vector and Agrobacterium tumefaciens-mediated gene transfer. In planta the recombinant synthase polymerised plant-derived UDP-glucose and UDP-glucuronic acid to form type 3 polysaccharide. Expression of the cps3S gene was detected by RT-PCR and production of the pneumococcal polysaccharide was detected in tobacco leaf extracts by double immunodiffusion, Western blotting and high-voltage paper electrophoresis. Because it is used a component of anti-pneumococcal vaccines, the immunogenicity of the plant-derived type 3 polysaccharide was tested. Mice immunised with extracts from recombinant plants were protected from challenge with a lethal dose of pneumococci in a model of pneumonia and the immunised mice had significantly elevated levels of serum anti-pneumococcal polysaccharide antibodies. This study provides the proof of the principle that bacterial polysaccharide can be successfully synthesised in plants and that these recombinant polysaccharides could be used as vaccines to protect against life-threatening infections

Lead optimization of a pyrazole sulfonamide series of trypanosoma brucei N -myristoyltransferase inhibitors:Identification and evaluation of CNS penetrant compounds as potential treatments for stage 2 human african trypanosomiasis

[Image: see text] Trypanosoma bruceiN-myristoyltransferase (TbNMT) is an attractive therapeutic target for the treatment of human African trypanosomiasis (HAT). From previous studies, we identified pyrazole sulfonamide, DDD85646 (1), a potent inhibitor of TbNMT. Although this compound represents an excellent lead, poor central nervous system (CNS) exposure restricts its use to the hemolymphatic form (stage 1) of the disease. With a clear clinical need for new drug treatments for HAT that address both the hemolymphatic and CNS stages of the disease, a chemistry campaign was initiated to address the shortfalls of this series. This paper describes modifications to the pyrazole sulfonamides which markedly improved blood–brain barrier permeability, achieved by reducing polar surface area and capping the sulfonamide. Moreover, replacing the core aromatic with a flexible linker significantly improved selectivity. This led to the discovery of DDD100097 (40) which demonstrated partial efficacy in a stage 2 (CNS) mouse model of HAT