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Search Results: 1 - 10 of 302562 matches for " McCall Philip J "
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“Sexual” Population Structure and Genetics of the Malaria Agent P. falciparum
Themba Mzilahowa, Philip J. McCall, Ian M. Hastings
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0000613
Abstract: The population genetics and structure of P. falciparum determine the rate at which malaria evolves in response to interventions such as drugs and vaccines. This has been the source of considerable recent controversy, but here we demonstrate the organism to be essentially sexual, in an area of moderately high transmission in the Lower Shire Valley, Malawi. Seven thousand mosquitoes were collected and dissected, and genetic data were obtained on 190 oocysts from 56 infected midguts. The oocysts were genotyped at three microsatellite loci and the MSP1 locus. Selfing rate was estimated as 50% and there was significant genotypic linkage disequilibrium (LD) in the pooled oocysts. A more appropriate analysis searching for genotypic LD in outcrossed oocysts and/or haplotypic LD in the selfed oocysts found no evidence for LD, indicating that the population was effectively sexual. Inbreeding estimates at MSP1 were higher than at the microsatellites, possibly indicative of immune action against MSP1, but the effect was confounded by the probable presence of null mutations. Mating appeared to occur at random in mosquitoes and evidence regarding whether malaria clones in the same host were related (presumably through simultaneous inoculation in the same mosquito bite) was ambiguous. This is the most detailed genetic analysis yet of P. falciparum sexual stages, and shows P. falciparum to be a sexual organism whose genomes are in linkage equilibrium, which acts to slow the emergence of drug resistance and vaccine insensitivity, extending the likely useful therapeutic lifespan of drugs and vaccines.
Redesigned and chemically-modified hammerhead ribozymes with improved activity and serum stability
Philip Hendry, Maxine J McCall, Tom S Stewart, Trevor J Lockett
BMC Chemical Biology , 2004, DOI: 10.1186/1472-6769-4-1
Abstract: A series of hammerhead ribozyme derivatives, varying in their hybridising arm length and size of helix II, were tested in vitro for cleavage of RNA derived from the carbamoyl phosphate synthetase II gene of Plasmodium falciparum. Against a 550-nt transcript the most efficient (t1/2 = 26 seconds) was a miniribozyme with helix II reduced to a single G-C base pair and with twelve nucleotides in each hybridising arm. Miniribozymes of this general design were targeted to three further sites, and they demonstrated exceptional cleavage activity. A series of chemically modified derivatives was prepared and examined for cleavage activity and stability in human serum. One derivative showed a 103-fold increase in serum stability and a doubling in cleavage efficiency compared to the unmodified miniribozyme. A second was almost 104-fold more stable and only 7-fold less active than the unmodified parent.Hammerhead ribozyme derivatives in which helix II is reduced to a single G-C base pair cleave long RNA substrates very efficiently in vitro. Using commonly available phosphoramidites and reagents, two patterns of nucleotide substitution in this derivative were identified which conferred both good cleavage activity against long RNA targets and good stability in human serum.Hammerhead ribozymes were discovered as self-cleaving motifs in a number of small, circular, pathogenic RNAs in plants [1-3]. Uhlenbeck [4] showed that the ribozyme was able to act in a bimolecular fashion as a true enzyme, ie each ribozyme was able to cleave multiple substrates. Haseloff and Gerlach [5] divided the hammerhead into a form in which the majority of the conserved nucleotides were located on the enzyme strand, with the only sequence requirements for the substrate being UH (H = A, U or C) [6-8]. Since 1988 this configuration, as shown in Figure 1, has been the paradigm for hammerhead ribozyme design. Hammerhead ribozymes are sequence-specific RNA cleaving agents with the potential to control the expre
Entomological indices of malaria transmission in Chikhwawa district, Southern Malawi
Mzilahowa Themba,Hastings Ian M,Molyneux Malcolm E,McCall Philip J
Malaria Journal , 2012, DOI: 10.1186/1475-2875-11-380
Abstract: Background Although malaria is highly prevalent throughout Malawi, little is known of its transmission dynamics. This paper describes the seasonal activity of the different vectors, human biting indices, sporozoite rates and the entomological inoculation rate in a low-lying rural area in southern Malawi. Methods Vectors were sampled over 52 weeks from January 2002 to January 2003, by pyrethrum knockdown catch in two villages in Chikhwawa district, in the Lower Shire Valley. Results In total, 7,717 anophelines were collected of which 55.1% were Anopheles gambiae sensu lato and 44.9% were Anopheles funestus. Three members of the An. gambiae complex were identified by PCR: Anopheles arabiensis (75%) was abundant throughout the year, An. gambiae s.s. (25%) was most common during the wet season and Anopheles quadriannulatus occurred at a very low frequency (n=16). An. funestus was found in all samples but was most common during the dry season. Anopheles gambiae s.s. and An. funestus were highly anthropophilic with human blood indices of 99.2% and 96.3%, respectively. Anopheles arabiensis had fed predominantly on humans (85.0%) and less commonly on cattle (10.9%; 1.2% of blood meals were of mixed origin). Plasmodium falciparum (192/3,984) and Plasmodium malariae (1/3,984) sporozoites were detected by PCR in An. arabiensis (3.2%) and An. funestus (4.5%), and in a significantly higher proportion of An. gambiae s.s. (10.6%)(p<0.01). All three vectors were present throughout the year and malaria transmission occurred in every month, although with greatest intensity during the rainy season (January to April). The combined human blood index exceeded 92% and the P. falciparum sporozoite rate was 4.8%, resulting in estimated inoculation rates of 183 infective bites/ person per annum, or an average rate of ~15 infective bites/person/month. Conclusions The results demonstrate the importance of An. gambiae s.s., An. arabiensis and An. funestus in driving the high levels of malaria transmission in the south of Malawi. Sustained and high coverage or roll out of current approaches to malaria control (primarily insecticide-treated bed nets and indoor residual house spraying) in the area are likely to reduce the observed high malaria transmission rate and consequently the incidence of human infections, unless impeded by increasing resistance of vectors to insecticides.
Investigating the Cosmic-Ray Ionization Rate in the Galactic Diffuse Interstellar Medium through Observations of H3+
Nick Indriolo,Benjamin J. McCall
Physics , 2011, DOI: 10.1088/0004-637X/745/1/91
Abstract: Observations of H3+ in the Galactic diffuse interstellar medium (ISM) have led to various surprising results, including the conclusion that the cosmic-ray ionization rate (zeta_2) is about 1 order of magnitude larger than previously thought. The present survey expands the sample of diffuse cloud sight lines with H3+ observations to 50, with detections in 21 of those. Ionization rates inferred from these observations are in the range (1.7+-1.3)x10^-16 s^-1
Empathy Diminishes Prejudice: Active Perspective-Taking, Regardless of Target and Mortality Salience, Decreases Implicit Racial Bias  [PDF]
Travis J. Pashak, McCall A. Conley, Drew J. Whitney, Samuel R. Oswald, Stephanie G. Heckroth, Evan M. Schumacher
Psychology (PSYCH) , 2018, DOI: 10.4236/psych.2018.96082
Abstract: Racism, and particularly the oppression of Black citizens, remains a significant problem in the United States. This manuscript reports on an experiment studying the effects of mortality salience and active perspective-taking empathy on racial bias. Specifically, social empathy was hypothesized to counteract the increased in-group preferential bias typical of those primed with mortality salience. The sample consisted of n = 111 White emerging adults affiliated with a small Midwest American university. Death anxiety and active perspective-taking were experimentally manipulated, and the dependent variables were implicit bias change scores (pre-test versus post-test on the Race-Related Implicit Association Test using White/Black faces) and explicit racial prejudice (self-report scores on the Quick Discrimination Inventory and Scale of Ethnocultural Empathy). The four experimental groups did not differ on implicit bias change scores or explicit discrimination scores—neither main effects nor interaction effects were statistically significant. However, the QDI and SEE were correlated (r = .76, p > .001), thus supporting their construct validity, and the pre-scores on the Race IAT across the whole sample were statistically significantly higher than the post-scores, with a moderate effect size (t(110) = 3.13, p = .002, eta-squared = .08). Findings appear to indicate that engaging in active perspective-taking, regardless of the race of the target and regardless of the presence of mortality salience, leads to decreased implicit racial prejudice. Empathy training in various clinical and educational settings could lead to a reduction in prejudiced attitudes, and ultimately aid in the dismantling of American racism.
Novel therapies for treating atrial fibrillation  [PDF]
Raj Parikh, Philip J. Kadowitz
World Journal of Cardiovascular Diseases (WJCD) , 2012, DOI: 10.4236/wjcd.2012.24040
Abstract: Atrial fibrillation is the most common cardiac arrhythmia and is a major risk factor for stroke, heart failure, and death. Current treatments focus on anti-coagulation as well as rate-control and rhythm-control strategies. Frequent INR checks associated with warfarin along with several adverse side effects of anti-arrhythmics have propelled investigations into novel treatments for atrial fibrillation. Research is focused not only on pioneering new pharmacological antico- agulation and anti-arrhythmic agents but also on improving surgical techniques in hopes of treating the arrhythmia. Here, we first briefly discuss the current treatment options, both pharmacological and non-pharmacological, for atrial fibrillation. We then present a focused review of recent animal and human investigations that examine the use of novel an-ticoagulation agents, mechanisms of new anti-arrhythmics, analyze potential triggers of atrial fibrillation, and highlight the role of genetics in atrial fibrillation.
Disease Development Caused by Ascochyta rabiei on Chickpea Detached-Leaves in Petri Dishes  [PDF]
Nunung Harijati, Philip J. Keane
American Journal of Plant Sciences (AJPS) , 2012, DOI: 10.4236/ajps.2012.310165
Abstract: A study using detached-leaves aimed to improve selection method. The improving method was done by scoring both disease symptom and lesion size. The research was begun by selecting agar concentration and dose of conidia that could distinguish response of very susceptible or resistant chickpea genotype. The result was used to determine disease severity (DS) and disease incident (DI) of eight genotypes that were previously tested in the field. Results of the tested agar concentration and dose of conidia showed that 1.5% and 2% agar were good to determine susceptible or resistant genotype; while 1 × 105 or 5 × 104 conidia dose was suitable for inoculation. The formula of DS (no. of leaflets in category × category value/Total no. of leaflets ×10) × 100, and DI (no. leaflets with pycnidial lesions + no. leaflets with necrotic lesions)/Total no. of leaflets × 100 successfully measured genotype response. The lesions development on detached leaves of the susceptible cultivar (Lasseter) began as circular, pale-colored areas, extending to the area covered by the drop of inoculum, then became light brown and finally dark brown. However, the response of resistant line (FLIP508) was restricted in area (and often confined to a tiny speck) surrounded by chlorosis or drying of the tissue.
The malaria vectors of the Lower Shire valley, Malawi
A A Spiers, T Mzilahowa, D Atkinson, P J McCall
Malawi Medical Journal , 2002,
Abstract: The aim of this study was to characterise breeding sites and climatic factors that influence the abundance of malaria vectors in the Lower Shire valley, Malawi. We regularly sampled adult and larval mosquitoes over the transition periods between the wet and dry seasons during 2000 and 2001. Three potential malaria vectors, An. arabiensis, An. gambiae sensu stricto and An. funestus, and a fourth non-vector species An. quadriannulatus, were identified. (This is the first record of An. quadriannulatus in Malawi). These four species bred predominately in larger water bodies, particularly rice paddies, and to a lesser extent in boreholes and puddles. Smaller temporary pools and puddles evaporated too quickly to permit the completion of larval development. Abundance of An. gambiae s.l. was closely associated with minimum temperatures. We discuss the relevance of the findings to malaria vector control in Malawi. [Malawi Med J. Vol.14(1) 2002: 4-7]
Remainders of power series
J. D. McCall,G. H. Fricke,W. A. Beyer
International Journal of Mathematics and Mathematical Sciences , 1979, DOI: 10.1155/s0161171279000223
Abstract: Suppose ¢ ‘n=0 ¢ anzn has radius of convergence R and N(z)=| ¢ ‘n=N ¢ anzn|. Suppose |z1|<|z2| N(z) ¢ € ‰for ¢ € ‰z μT}. Two questions are asked: (a) can S be cofinite? (b) can S be infinite? This paper provides some answers to these questions. The answer to (a) is no, even if T=z2. The answer to (b) is no, for T=z2 if liman=a ¢ ‰ 0. Examples show (b) is possible if T=z2 and for T a neighborhood of z2.
Assessing the Relationship between Vector Indices and Dengue Transmission: A Systematic Review of the Evidence
Leigh R. Bowman,Silvia Runge-Ranzinger,P. J. McCall
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0002848
Abstract: Background Despite doubts about methods used and the association between vector density and dengue transmission, routine sampling of mosquito vector populations is common in dengue-endemic countries worldwide. This study examined the evidence from published studies for the existence of any quantitative relationship between vector indices and dengue cases. Methodology/Principal Findings From a total of 1205 papers identified in database searches following Cochrane and PRISMA Group guidelines, 18 were included for review. Eligibility criteria included 3-month study duration and dengue case confirmation by WHO case definition and/or serology. A range of designs were seen, particularly in spatial sampling and analyses, and all but 3 were classed as weak study designs. Eleven of eighteen studies generated Stegomyia indices from combined larval and pupal data. Adult vector data were reported in only three studies. Of thirteen studies that investigated associations between vector indices and dengue cases, 4 reported positive correlations, 4 found no correlation and 5 reported ambiguous or inconclusive associations. Six out of 7 studies that measured Breteau Indices reported dengue transmission at levels below the currently accepted threshold of 5. Conclusions/Significance There was little evidence of quantifiable associations between vector indices and dengue transmission that could reliably be used for outbreak prediction. This review highlighted the need for standardized sampling protocols that adequately consider dengue spatial heterogeneity. Recommendations for more appropriately designed studies include: standardized study design to elucidate the relationship between vector abundance and dengue transmission; adult mosquito sampling should be routine; single values of Breteau or other indices are not reliable universal dengue transmission thresholds; better knowledge of vector ecology is required.
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