1,264 research outputs found
Mathematical Modeling of Malaria Infection with Innate and Adaptive Immunity in Individuals and Agent-Based Communities
Background: Agent-based modeling of Plasmodium falciparum infection offers an attractive alternative to the conventional Ross-Macdonald methodology, as it allows simulation of heterogeneous communities subjected to realistic transmission (inoculation patterns). Methodology/Principal Findings: We developed a new, agent based model that accounts for the essential in-host processes: parasite replication and its regulation by innate and adaptive immunity. The model also incorporates a simplified version of antigenic variation by Plasmodium falciparum. We calibrated the model using data from malaria-therapy (MT) studies, and developed a novel calibration procedure that accounts for a deterministic and a pseudo-random component in the observed parasite density patterns. Using the parasite density patterns of 122 MT patients, we generated a large number of calibrated parameters. The resulting data set served as a basis for constructing and simulating heterogeneous agent-based (AB) communities of MT-like hosts. We conducted several numerical experiments subjecting AB communities to realistic inoculation patterns reported from previous field studies, and compared the model output to the observed malaria prevalence in the field. There was overall consistency, supporting the potential of this agent-based methodology to represent transmission in realistic communities. Conclusions/Significance: Our approach represents a novel, convenient and versatile method to model Plasmodiu
Investor heterogeneity and the cross-section of U.K. investment trust performance
We use the upper and lower bounds derived by Ferson and Lin (2010) to examine the impact of investor heterogeneity on the performance of U.K. investment trusts relative to alternative linear factor models. We find using the upper bounds that investor heterogeneity has an important impact for nearly all investment trusts. The upper bounds are large in economic terms and significantly different from zero. We find no evidence of any trusts where all investors agree on the sign of performance beyond what we expect by chance. Using the lower bound, we find that trusts with a larger disagreement about trust performance have a weaker relation between the trust premium and past Net Asset Value (NAV) performance
Copy number variation in Parkinson's disease
A central theme of human genetic studies is to understand genomic variation and how this underlies the inherited basis of disease. Genomic variation can provide increased biological understanding of disease processes, which is necessary to develop future treatments. Recent technological advances have highlighted the role of copy number variants in normal and pathological phenotypic expression. These applications have been used in studies of Parkinson's disease, a common, late-onset, progressive neurodegenerative disorder. At present the main therapeutic approach is administration of symptom-alleviating drugs, which neither reverses the disease process nor halts its progression. However, the generation of in vivo model systems and development of novel disease intervention strategies for Parkinson's disease have come from research on monogenic forms of the disorder, including those caused by copy number variants. Here, we review the role of copy number variants and the mechanistic insights they have provided on the pathogenesis of Parkinson's disease
The Neutron Electric Dipole Moment and CP-violating Couplings in the Supersymmetric Standard Model without R-parity
We analyze the neutron electric dipole moment (EDM) in the Minimal
Supersymmetric Model with explicit R-parity violating terms. The leading
contribution to the EDM occurs at the 2-loop level and is dominated by the
chromoelectric dipole moments of quarks, assuming there is no tree-level
mixings between sleptons and Higgs bosons or between leptons and gauginos.
Based on the experimental constraint on the neutron EDM, we set limits on the
imaginary parts of complex couplings and
due to the virtual b-loop or tau-loop.Comment: final manuscript to appear in Phys. Rev. D, 15 pages, latex, 4
figures include
Characterization of complex networks: A survey of measurements
Each complex network (or class of networks) presents specific topological
features which characterize its connectivity and highly influence the dynamics
of processes executed on the network. The analysis, discrimination, and
synthesis of complex networks therefore rely on the use of measurements capable
of expressing the most relevant topological features. This article presents a
survey of such measurements. It includes general considerations about complex
network characterization, a brief review of the principal models, and the
presentation of the main existing measurements. Important related issues
covered in this work comprise the representation of the evolution of complex
networks in terms of trajectories in several measurement spaces, the analysis
of the correlations between some of the most traditional measurements,
perturbation analysis, as well as the use of multivariate statistics for
feature selection and network classification. Depending on the network and the
analysis task one has in mind, a specific set of features may be chosen. It is
hoped that the present survey will help the proper application and
interpretation of measurements.Comment: A working manuscript with 78 pages, 32 figures. Suggestions of
measurements for inclusion are welcomed by the author
The Role of Individual Variables, Organizational Variables and Moral Intensity Dimensions in Libyan Management Accountantsβ Ethical Decision Making
This study investigates the association of a broad set of variables with the ethical decision making of management accountants in Libya. Adopting a cross-sectional methodology, a questionnaire including four different ethical scenarios was used to gather data from 229 participants. For each scenario, ethical decision making was examined in terms of the recognition, judgment and intention stages of Restβs model. A significant relationship was found between ethical recognition and ethical judgment and also between ethical judgment and ethical intention, but ethical recognition did not significantly predict ethical intentionβthus providing support for Restβs model. Organizational variables, age and educational level yielded few significant results. The lack of significance for codes of ethics might reflect their relative lack of development in Libya, in which case Libyan companies should pay attention to their content and how they are supported, especially in the light of the under-development of the accounting profession in Libya. Few significant results were also found for gender, but where they were found, males showed more ethical characteristics than females. This unusual result reinforces the dangers of gender stereotyping in business. Personal moral philosophy and moral intensity dimensions were generally found to be significant predictors of the three stages of ethical decision making studied. One implication of this is to give more attention to ethics in accounting education, making the connections between accounting practice and (in Libya) Islam. Overall, this study not only adds to the available empirical evidence on factors affecting ethical decision making, notably examining three stages of Restβs model, but also offers rare insights into the ethical views of practising management accountants and provides a benchmark for future studies of ethical decision making in Muslim majority countries and other parts of the developing world
Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.
To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo
A Sub-Microscopic Gametocyte Reservoir Can Sustain Malaria Transmission
Novel diagnostic tools, including PCR and high field gradient magnetic fractionation (HFGMF), have improved detection of asexual Plasmodium falciparum parasites and especially infectious gametocytes in human blood. These techniques indicate a significant number of people carry gametocyte densities that fall below the conventional threshold of detection achieved by standard light microscopy (LM).To determine how low-level gametocytemia may affect transmission in present large-scale efforts for P. falciparum control in endemic areas, we developed a refinement of the classical Ross-Macdonald model of malaria transmission by introducing multiple infective compartments to model the potential impact of highly prevalent, low gametocytaemic reservoirs in the population. Models were calibrated using field-based data and several numerical experiments were conducted to assess the effect of high and low gametocytemia on P. falciparum transmission and control. Special consideration was given to the impact of long-lasting insecticide-treated bed nets (LLIN), presently considered the most efficient way to prevent transmission, and particularly LLIN coverage similar to goals targeted by the Roll Back Malaria and Global Fund malaria control campaigns. Our analyses indicate that models which include only moderate-to-high gametocytemia (detectable by LM) predict finite eradication times after LLIN introduction. Models that include a low gametocytemia reservoir (requiring PCR or HFGMF detection) predict much more stable, persistent transmission. Our modeled outcomes result in significantly different estimates for the level and duration of control needed to achieve malaria elimination if submicroscopic gametocytes are included.It will be very important to complement current methods of surveillance with enhanced diagnostic techniques to detect asexual parasites and gametocytes to more accurately plan, monitor and guide malaria control programs aimed at eliminating malaria
Parental and infant characteristics and childhood leukemia in Minnesota
<p>Abstract</p> <p>Background</p> <p>Leukemia is the most common childhood cancer. With the exception of Down syndrome, prenatal radiation exposure, and higher birth weight, particularly for acute lymphoid leukemia (ALL), few risk factors have been firmly established. Translocations present in neonatal blood spots and the young age peak of diagnosis suggest that early-life factors are involved in childhood leukemia etiology.</p> <p>Methods</p> <p>We investigated the association between birth characteristics and childhood leukemia through linkage of the Minnesota birth and cancer registries using a case-cohort study design. Cases included 560 children with ALL and 87 with acute myeloid leukemia (AML) diagnoses from 28 days to 14 years. The comparison group was comprised of 8,750 individuals selected through random sampling of the birth cohort from 1976β2004. Cox proportional hazards regression specific for case-cohort studies was used to compute hazard ratios (HR) and 95% confidence intervals (CIs).</p> <p>Results</p> <p>Male sex (HR = 1.41, 95% CI 1.16β1.70), white race (HR = 2.32, 95% CI 1.13β4.76), and maternal birth interval β₯ 3 years (HR = 1.31, 95% CI 1.01β1.70) increased ALL risk, while maternal age increased AML risk (HR = 1.21/5 year age increase, 95% CI 1.0β1.47). Higher birth weights (>3798 grams) (HRALL = 1.46, 1.08β1.98; HRAML = 1.97, 95% CI 1.07β3.65), and one minute Apgar scores β€ 7 (HRALL = 1.30, 95% CI 1.05β1.61; HRAML = 1.62, 95% CI 1.01β2.60) increased risk for both types of leukemia. Sex was not a significant modifier of the association between ALL and other covariates, with the exception of maternal education.</p> <p>Conclusion</p> <p>We confirmed known risk factors for ALL: male sex, high birth weight, and white race. We have also provided data that supports an increased risk for AML following higher birth weights, and demonstrated an association with low Apgar scores.</p
Recruitment Potential of a Green Alga Ulva flexuosa Wulfen Dark Preserved Zoospore and Its Development
The recruitment potential and the ability of Ulva flexuosa Wulfen zoospores to survive darkness were tested under different conditions in the present study. The dark preserved zoospore was cultured under a two-factor experimental design to test the effect of salinity and nitrate, effect of salinity and phosphate, effect of light and salinity, and effect of light and phosphate. The recruitment (germination and growth) of zoospores was significantly affected by light and salinity. The nitrate concentration of 20 Β΅mol.lβ1 was found to initiate the process of germination and its subsequent growth and, its effect appeared greatest under 25 psu condition. While nitrate enhances the growth of biomass more than phosphate, both show a positive interactive effect on biomass increase when crossed with salinity. The combined effect of 25 psu salinity and 8 Β΅mol.lβ1 phosphate exhibited higher biomass growth. There was a significant effect of light and salinity on the biomass of zoospore, though there was no significant interaction between the two factors. There was an increase in biomass of growing zoospores to increase in light intensity and 80 Β΅mol.mβ2.sβ1 of light intensity was considered optimal. Similarly, high light intensity condition favored higher biomass growth and there was significant interaction between light (80 Β΅mol. mβ2. sβ1) and phosphate (4 Β΅mol. lβ1) in high salinity (35 psu) condition. The result of this study showed that dark preserved zoospores of U. flexuosa have the potential for recruitment and it gives us an understanding how different factors play a role in the process of recruitment
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