59,632 research outputs found
Letter from D. M. Clements to S. B. Simmons
No full textLetter from D. M. Clements to S. B. Simmons, concerning FFA and NFA alumni
Spatial heterogeneity of parasite co-infection: Determinants and geostatistical prediction at regional scales.
No full textMultiple parasite infections are widespread in the developing world and understanding their geographical distribution is important for spatial targeting of differing intervention packages. We investigated the spatial epidemiology of mono- and co-infection with helminth parasites in East Africa and developed a geostatistical model to predict infection risk. The data used for the analysis were taken from standardised school surveys of Schistosoma mansoni and hookworm (Ancylostoma duodenale/Necator americanus) carried out between 1999 and 2005 in East Africa. Prevalence of mono- and co-infection was modelled using satellite-derived environmental and demographic variables as potential predictors. A Bayesian multi-nominal geostatistical model was developed for each infection category for producing maps of predicted co-infection risk. We show that heterogeneities in co-infection with S. mansoni and hookworm are influenced primarily by the distribution of S. mansoni, rather than the distribution of hookworm, and that temperature, elevation and distance to large water bodies are reliable predictors of the spatial large-scale distribution of co-infection. On the basis of these results, we developed a validated geostatistical model of the distribution of co-infection at a scale that is relevant for planning regional disease control efforts that simultaneously target multiple parasite species
Bayesian spatial analysis of a national urinary schistosomiasis questionnaire to assist geographic targeting of schistosomiasis control in Tanzania, East Africa.
No full textSpatial modelling was applied to self-reported schistosomiasis data from over 2.5 million school students from 12,399 schools in all regions of mainland Tanzania. The aims were to derive statistically robust prevalence estimates in small geographical units (wards), to identify spatial clusters of high and low prevalence and to quantify uncertainty surrounding prevalence estimates. The objective was to permit informed decision-making for targeting of resources by the Tanzanian national schistosomiasis control programme. Bayesian logistic regression models were constructed to investigate the risk of schistosomiasis in each ward, based on the prevalence of self-reported schistosomiasis and blood in urine. Models contained covariates representing climatic and demographic effects and random effects for spatial clustering. Degree of urbanisation, median elevation of the ward and median normalised difference vegetation index (NDVI) were significantly and negatively associated with schistosomiasis prevalence. Most regions contained wards that had >95% certainty of schistosomiasis prevalence being >10%, the selected threshold for bi-annual mass chemotherapy of school-age children. Wards with >95% certainty of schistosomiasis prevalence being >30%, the selected threshold for annual mass chemotherapy of school-age children, were clustered in north-western, south-western and south-eastern regions. Large sample sizes in most wards meant raw prevalence estimates were robust. However, when uncertainties were investigated, intervention status was equivocal in 6.7-13.0% of wards depending on the criterion used. The resulting maps are being used to plan the distribution of praziquantel to participating districts; they will be applied to prioritising control in those wards where prevalence was unequivocally above thresholds for intervention and might direct decision-makers to obtain more information in wards where intervention status was uncertain
Molecular effects of novel mutations in Hesx1/HESX1 associated with human pituitary disorders
No full textThe homeobox gene Hesx1/HESX1 has been implicated in the establishment of anterior pattern in the central nervous system (CNS) in a number of vertebrate species. Its role in pituitary development has been documented through loss-of-function studies in the mouse. A homozygous missense point mutation resulting in a single amino acid substitution, Arg160Cys (R160C), is associated with a heritable form of the human condition of septo-optic dysplasia (SOD). We have examined the phenotype of affected members in this pedigree in more detail and demonstrate for the first time a genetic basis for midline defects associated with an undescended or ectopic posterior pituitary. A similar structural pituitary abnormality was observed in a second patient heterozygous for another mutation in HESX1, Ser170Leu (S170L). Association of S170L with a pituitary phenotype may be a direct consequence of the HESX1 mutation since S170L is also associated with a dominant familial form of pituitary disease. However, a third mutation in HESX1, Asn125Ser (N125S), occurs at a high frequency in the Afro-Caribbean population and may therefore reflect a population-specific polymorphism. To investigate the molecular basis for these clinical phenotypes, we have examined the impact of these mutations on the regulatory functions of HESX1. We show that Hesx1 is a promoter-specific transcriptional repressor with a minimal 36 amino acid repression domain which can mediate promoter-specific repression by suppressing the activity of homeodomain-containing activator proteins. Mutations in HESX1 associated with pituitary disease appear to modulate the DNA-binding affinity of HESX1 rather than its transcriptional activity. Wild-type HESX1 binds a dimeric homeodomain site with high affinity (K-d 31 nM) whilst HESX1(S170L) binds with a 5-fold lower activity (K-d 150 nM) and HESX1(R160C) does not bind at all. Although HESX1(R160C) has only been shown to be associated with the SOD phenotype in children homozygous for the mutation, HESX1(R160C) can inhibit DNA binding by wild-type HESX1 both in vitro and in vivo in cell culture. This dominant negative activity of HESX1(R160C) is mediated by the Hesx1 repression domain, supporting the idea that the repression domain is implicated in interactions between homeodomain proteins. Our data suggest a possible molecular paradigm for the dominant inheritance observed in some pituitary disorders
1ST MEASUREMENT OF GAMMA(D(S)(+)-]MU+NU)/GAMMA(D(S)(+)-]PHI-PI+)
No full textComplete Author List:
ACOSTA D, ATHANAS M, MASEK G, PAAR H, BEAN A, GRONBERG J, KUTSCHKE R, MENARY S, MORRISON RJ, NAKANISHI S, NELSON HN, NELSON TK, RICHMAN JD, RYD A, TAJIMA H, SCHMIDT D, SPERKA D, WITHERELL MS, PROCARIO M, YANG S, BALEST R, CHO K, DAOUDI M, FORD WT, JOHNSON DR, LINGEL K, LOHNER M, RANKIN P, SMITH JG, ALEXANDER JP, BEBEK C, BERKELMAN K, BESSON D, BROWDER TE, CASSEL DG, CHO HA, COFFMAN DM, DRELL PS, EHRLICH R, GALIK RS, GARCIASCIVERES M, GEISER B, GITTELMAN B, GRAY SW, HARTILL DL, HELTSLEY BK, JONES CD, JONES SL, KANDASWAMY J, KATAYAMA N, KIM PC, KREINICK DL, LUDWIG GS, MASUI J, MEVISSEN J, MISTRY NB, NG CR, NORDBERG E, OGG M, PATTERSON JR, PETERSON D, RILEY D, SALMAN S, SAPPER M, WORDEN H, WURTHWEIN F, AVERY P, FREYBERGER A, RODRIGUEZ J, STEPHENS R, YELTON J, CINABRO D, HENDERSON S, KINOSHITA K, LIU T, SAULNIER M, SHEN F, WILSON R, YAMAMOTO H, ONG B, SELEN M, SADOFF AJ, AMMAR R, BALL S, BARINGER P, COPPAGE D, COPTY N, DAVIS R, HANCOCK N, KELLY M, KWAK N, LAM H, KUBOTA Y, LATTERY M, NELSON JK, PATTON S, PERTICONE D, POLING R, SAVINOV V, SCHRENK S, WANG R, ALAM MS, KIM IJ, NEMATI B, ONEILL JJ, SEVERINI H, SUN CR, ZOELLER MM, CRAWFORD G, DAUBENMIER CM, FULTON R, FUJINO D, GAN KK, HONSCHEID K, KAGAN H, KASS R, LEE J, MALCHOW R, MORROW F, SKOVPEN Y, SUNG M, WHITE C, WHITMORE J, WILSON P, BUTLER F, FU X, KALBFLEISCH G, LAMBRECHT M, ROSS WR, SKUBIC P, SNOW J, WANG PL, WOOD M, BORTOLETTO D, BROWN DN, FAST J, MCILWAIN RL, MIAO T, MILLER DH, MODESITT M, SCHAFFNER SF, SHIBATA EI, SHIPSEY IPJ, WANG PN, BATTLE M, ERNST J, KROHA H, ROBERTS S, SPARKS K, THORNDIKE EH, WANG CH, DOMINICK J, SANGHERA S, SHELKOV V, SKWARNICKI T, STROYNOWSKI R, VOLOBOUEV I, ZADOROZHNY P, ARTUSO M, HE D, GOLDBERG M, HORWITZ N, KENNETT R, MONETI GC, MUHEIM F, MUKHIN Y, PLAYFER S, ROZEN Y, STONE S, THULASIDAS M, VASSEUR G, ZHU G, BARTELT J, CSORNA SE, EGYED Z, JAIN V, SHELDON P, AKERIB DS, BARISH B, CHADHA M, CHAN S, COWEN DF, EIGEN G, MILLER JS, OGRADY C, URHEIM J, WEINSTEIN A
Pooling of Forecasts
No full textWe consider forecasting using a combination, when no model coincides with a non-constant data generation process (DGP). Practical experience suggests that combining forecasts adds value, and can even dominate the best individual device. We show why this can occur when forecasting models are differentially mis-specified, and is likely to occur when the DGP is subject to deterministic shifts. Moreover, averaging may then dominate over estimated weights in the combination. Finally, it cannot be proved that only non-encompassed devices should be retained in the combination. Empirical and Monte Carlo illustrations confirm the analysis.
Roller Spacing in the Float Glass Process
No full textCase Studies in Mathematical Modelling, Bradley R, Gibson R D and Cross M (editors), Pentech Press,1981, (sole author
Synthetic, Register-Specific, AAB Heterotrimers to Investigate Single Point Glycine Mutations in Osteogenesis Imperfecta
No full textOsteogenesis imperfecta (OI) is a
disease caused primarily by mutations
of glycine in the standard (Xaa-Yaa-Gly)<sub><i>n</i></sub> repeat of a type I collagen triple helix. Type I collagen is an
AAB heterotrimer which means that, depending on whether the A or B
chain is mutated, the glycine substitution will appear once or twice.
In this work we use designed axial charged pairs to self-assemble
an AAB triple helix with controlled composition and register. We then
substitute a single glycine of the B chain with alanine, serine, valine,
aspartate, or arginine and assess the impact on the structure and
folding of this OI mimic by CD, NMR, and restraint-guided modeling.
We find that alanine and serine substitutions are tolerated, resulting
in localized disruptions to the triple helix structure, while bulkier
amino acids result in alternatively folded structures. This work demonstrates
the potential of axial charged pairs to control the structure of low
stability triple helices and also helps to elucidate the structure
and folding challenges associated with OI-type mutations in collagen
A 2 h periodic variation in the low-mass X-ray binary Ser X-1
No full textSpectroscopy of the low-mass X-ray binary Ser X-1 using the Gran Telescopio Canarias have revealed a ?2 h periodic variability that is present in the three strongest emission lines. We tentatively interpret this variability as due to orbital motion, making it the first indication of the orbital period of Ser X-1. Together with the fact that the emission lines are remarkably narrow, but still resolved, we show that a main-sequence K dwarf together with a canonical 1.4 M? neutron star gives a good description of the system. In this scenario, the most likely place for the emission lines to arise is the accretion disc, instead of a localized region in the binary (such as the irradiated surface or the stream-impact point), and their narrowness is due instead to the low inclination (?10°) of Ser X-1
The suitability of anaerobic digesters on organic farms
No full textFood and energy security are two key environmental challenges currently faced by mankind. The principles behind organic farming are to promote environmental sustainability; however within the organic standards the use of renewable energy is only a suggested method with which to achieve this. If organic farmers can successfully utilise anaerobic digesters, they could contribute towards the provision of both food and energy security using one holistic system. Within this thesis, the suitability of anaerobic digesters on organic farms was explored using methods from ecological, sociological and environmental sciences. This enabled both the practical and theoretical issues behind the question of whether it is suitable for anaerobic digesters to be used on organic farms to be addressed.Field and laboratory experiments were used to compare the effects digestate and slurry had on earthworms, grass and weeds. Digestate and slurry had species dependent effects on earthworms during both LD50 / LT50 experiments and behavioural bioassays; Lumbricus terrestris survived longer in slurry and showed a behavioural preference towards slurry over digestate, whereas Eisenia fetida showed the opposite responses. Fertiliser application rates over 170 kg N ha-1 were found to be harmful to both species of earthworm. Suppressed germination effects were seen on thistles treated with digestate compared with no treatment (F0.56,19.66 =4.66, P < 0.01), whilst grass fertilised with digestate had a greater total mass than grass fertilised with slurry or left unfertilised (F2,27 =17.92, P < 0.001).Questionnaires and interviews were used to obtain a better understanding of the opinions farmers had about anaerobic digesters. Organic farmers believed renewable energy generation fitted well within organic principles, but using an anaerobic digester on an organic farm was less practical than on a conventional farm. This was due to multiple reasons including lack of information, poor associated finances, and that existing digesters are currently unsuitable for small organic farms. There was also support for anaerobic digesters to be on dairy farms- this was regardless of whether the farm was organic or conventional.Two case-study farms were used to assess the impact an anaerobic digester would have on the farms total GHG emissions. An anaerobic digester on the dairy farm was calculated to reduce GHG emissions by up to 24%, while for the mixed farm, the maximum reduction was by 20%. This was primarily due to the fact that the dairy farm benefitted from a higher volume of feedstock and proposed to use the biogas in a more energy efficient manner by producing electricity rather than vehicle fuel. Due to the high emissions associated with keeping livestock, both case studies needed to import additional feedstock if the farms were to achieve zero net GHG emissions.The answer to whether anaerobic digesters can be suitable for organic farms was judged on how well they complimented or conflicted with IFOAM’s definition of organic farming. Three main aspects of their definition were chosen and evidence from each chapter used to address the main question of the thesis. In conclusion, anaerobic digesters are theoretically suitable for use on organic farms, but are generally more practical for use on conventional farm systems. Across both farm systems the most suitable enterprises to adopt anaerobic digesters are dairy farms. This highlights the need for suitability of new systems to be assessed on a case-by-case scenario when trying to maximise positive impacts from new technologies
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