2,399 research outputs found
Learning from Neighbors about a Changing State
Agents learn about a changing state using private signals and past actions of
neighbors in a network. We characterize equilibrium learning and social
influence in this setting. We then examine when agents can aggregate
information well, responding quickly to recent changes. A key sufficient
condition for good aggregation is that each individual's neighbors have
sufficiently different types of private information. In contrast, when signals
are homogeneous, aggregation is suboptimal on any network. We also examine
behavioral versions of the model, and show that achieving good aggregation
requires a sophisticated understanding of correlations in neighbors' actions.
The model provides a Bayesian foundation for a tractable learning dynamic in
networks, closely related to the DeGroot model, and offers new tools for
counterfactual and welfare analyses.Comment: minor revision tweaking exposition relative to v5 - which added new
Section 3.2.2, new Theorem 2, new Section 7.1, many local revision
Finite Element Analysis Of Modified Conebolt Under Static And Dynamic Loadings
Axisymmetric finite element models are developed to simulate static pull test and dynamic drop test of MCB33 (modified conebolt with full dedonding) using ABAQUS. Results from the numerical models are in reasonable agreement with the test results. A parametric study is performed considering various variables (i.e. friction, cone angle, material strength, etc.) to analyze the performance of MCB33. The results demonstrate that friction between the steel and resin, cone angle, and the Poisson’s ratio of the resin affect the static and dynamic behaviors of the rockbolt. These parameters can be modified to improve the current design and enhance the overall performance of the rockbolt
Regional center for complex colonoscopy: yield of neoplasia in patients with prior incomplete colonoscopy
Background and Aims
Incomplete colonoscopy increases the risk of incident proximal colon cancer postcolonoscopy. Incomplete colonoscopy is often followed by barium enema or CT colonography. We sought to describe the yield of completion colonoscopy in a regional center for complex colonoscopy.
Methods
This is a retrospective cohort study of 520 consecutive patients referred to a single colonoscopist over a 14-year period for completion colonoscopy after a previous incomplete examination.
Results
Colonoscopy was completed to the cecum in 506 of 520 patients (97.3%). A total of 913 conventional adenomas was removed in 277 patients (adenoma detection rate 53.3%). There were 184 adenomas ≥ 1 cm in size or with advanced pathology. There were 525 serrated-class lesions removed in 175 patients, including 54 sessile serrated polyps in 26 patients and 41 hyperplastic polyps greater than 1 cm in 26 patients. Nine colorectal cancers were found. We estimated that approximately 57% of the conventional adenomas, 58% of the sessile serrated polyps, 27% of the hyperplastic polyps, and all 9 cancers detected by the completion colonoscopy were beyond the extent of the previous examination.
Conclusions
The yield of completion colonoscopy in a cohort of patients with previous failed cecal intubation was substantial. Regional centers for complex colonoscopy can provide high rates of cecal intubation in cases of incomplete colonoscopy and high yields of lesions in these cases. The regional center for complex colonoscopy is an important medical service
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Investigating and exploiting the latency-associated expression of the human cytomegalovirus gene US28 in early myeloid lineage cells.
Human cytomegalovirus (HCMV) is a betaherpesvirus which establishes a lifelong persistent infection, underpinned by its ability to establish latent infection in early myeloid lineage cells, in the infected host. Although well controlled by a healthy immune system, HCMV causes pathological and life threatening disease in individuals with a compromised or immature immune response, which can come from primary HCMV infection or reactivation of latent infection. Although progress is being made in understanding the mechanisms by which HCMV maintains latency and reactivates, a better understanding is essential towards the aim of targeting and killing latently infected cells.
In this thesis, I will present evidence that the HCMV-encoded chemokine receptor homologue US28, which is expressed during latent infection of CD14+ monocytes, is necessary for maintaining HCMV latency in these monocytes and, in the absence of US28 protein expression, HCMV undergoes lytic infection. US28 expression was found to attenuate cellular signalling pathways in latently infected cells; in particular, MAP kinase and NFκB. Interestingly, deletion of the US28 gene or inhibition of the US28 protein resulted in the expression of lytic antigens which allowed detection of infected monocytes by the immune system. This observation may lead to a potential new immunotherapeutic strategy against latent HCMV.
Having demonstrated that US28 protein is expressed on the surface of latently infected monocytes, I tested whether a new fusion-toxin protein, called F49A-FTP, which binds US28 protein, could be used to target and kill latently infected cells. I developed a protocol for treating latently infected monocytes with F49A-FTP which resulted in a significant reduction in virus reactivation after monocyte differentiation to dendritic cells. I was also able to show that this treatment kills CD34+ progenitor cells, which were experimentally latently infected with HCMV, as well as latently infected monocytes from a healthy, seropositive blood donor.
Finally, during my investigations into the role of US28 during HCMV latency, a mass spectrometry screen was performed to measure changes in cellular protein expression when US28 protein is expressed in isolation, in THP-1 monocyte-like cell line. This identified CTCF, a transcription factor which appears to be modified by US28 in THP-1 cells. I showed that CTCF has a repressive effect on the HCMV MIEP, and that CTCF likely plays a role in HCMV latency.
In summary, this work provides insights into the role of US28 during HCMV latency, and proposes potential novel therapeutic strategies to kill latently infected cells.My PhD was funded by the Wellcome Trust, while my lab was funded by the Medical Research Council
A pan-Himalayan test of predictions on plant species richness based on primary production and water-energy dynamics
Spatial variation in plant species diversity is well-documented but an overarching first-principles theory for diversity variation is lacking. Chemical energy expressed as Net Primary Production (NPP) is related to a monotonic increase in species richness at a macroscale and supports one of the leading energy-productivity hypotheses, the More individuals Hypothesis. Alternatively, water-energy dynamics (WED) hypothesizes enhanced species richness when water is freely available and energy supply is optimal. This theoretical model emphasises the amount and duration of photosynthesis across the year and therefore we include the length of the growing season and its interaction with precipitation. This seasonal-WED model assumes that biotemperature and available water represent the photosynthetically active period for the plants and hence, is directly related to NPP, especially in temperate and alpine regions. This study aims to evaluate the above-mentioned theoretical models using interpolated elevational species richness of woody and herbaceous flowering plants of the entire Himalayan range based on data compiled from databases. Generalized linear models (GLM) and generalized linear mixed models (GLMM) were used to analyse species richness (elevational gamma diversity) in the six geopolitical sectors of the Himalaya. NPP, annual precipitation, potential evapotranspiration (derived by the Holdridge formula), and length of growing season were treated as the explanatory variables and the models were evaluated using the Akaike Information Criterion (AIC) and explained deviance. Both precipitation plus potential evapotranspiration (PET), and NPP explain plant species richness in the Himalaya. The seasonal-WED model explains the species richness trends of both plant life-forms in all sectors of the Himalayan range better than the NPP-model. Despite the linear precipitation term failing to precisely capture the amount of water available to plants, the seasonal-WED model, which is based on the thermodynamical transition between water phases, is reasonably good and can forecast peaks in species richness under different climate and primary production conditions.publishedVersio
Alveolar Macrophages Isolated Directly From Human Cytomegalovirus (HCMV)-Seropositive Individuals Are Sites of HCMV Reactivation In Vivo.
Human cytomegalovirus (HCMV) causes significant morbidity in the immunocompromised host. Following primary infection, the virus establishes latent infection in progenitor cells of the myeloid lineage. These cells exhibit limited viral gene transcription and no evidence of de novo virion production. It is well recognized that differentiation of latently infected myeloid progenitor cells to dendritic or macrophage-like cells permits viral reactivation in vitro. This has been used to support the concept that viral reactivation in HCMV carriers routinely occurs from such terminally differentiated myeloid cells in vivo. However, to date this has not been shown for in vivo-differentiated macrophages. This study is the first to demonstrate that alveolar macrophages from HCMV carriers express immediate early lytic genes and produce infectious virus. This supports the view, until now based on in vitro data, that terminally differentiated myeloid cells in vivo are sites of HCMV reactivation and potential centers of viral dissemination in latently infected individuals with no evidence of virus disease or dissemination.This work was supported by the UK Medical Research
Council (grant 0701279 to J. S.) and the National Institute for Health
Research UK Biomedical Research Centre (to J. S. and E. R. C.).This is the final published version. It first appeared at http://jid.oxfordjournals.org/content/211/12/1936
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