Constrained tGAP for generalisation between scales: the case of Dutch topographic data

This article presents the results of integrating large- and medium-scale data into a unified data structure. This structure can be used as a single non-redundant representation for the input data, which can be queried at any arbitrary scale between the source scales. The solution is based on the constrained topological Generalized Area Partition (tGAP), which stores the results of a generalization process applied to the large-scale dataset, and is controlled by the objects of the medium-scale dataset, which act as constraints on the large-scale objects. The result contains the accurate geometry of the large-scale objects enriched with the generalization knowledge of the medium-scale data, stored as references in the constraint tGAP structure. The advantage of this constrained approach over the original tGAP is the higher quality of the aggregated maps. The idea was implemented with real topographic datasets from The Netherlands for the large- (1:1000) and medium-scale (1:10,000) data. The approach is expected to be equally valid for any categorical map and for other scales as well

Estrogen use and early onset Alzheimer's disease: a population-based study

Estrogen use may be protective for Alzheimer's disease with late onset. However, the effects on early onset Alzheimer's disease are unclear. This issue was studied in a population based setting. For each female patient, a female control was matched on age (within 5 years) and place of residence. Information on estrogen use and other risk factors were, for cases (n=109) and controls (n=119), collected from the next of kin by structured interview. The strength of the association between estrogen use and early onset Alzheimer's disease was studied using conditional logistic regression with adjustment for age and education level. There was an inverse association between estrogen use and early onset Alzheimer's disease (adjusted odds ratio 0.34; 95% confidence interval 0.12-0.94). The study therefore suggests that estrogen use is beneficial to Alzheimer's disease with early onset

Constrained tGAP for generalisation between scales: the case of Dutch topographic data

This article presents the results of integrating large- and medium-scale data into a unified data structure. This structure can be used as a single non-redundant representation for the input data, which can be queried at any arbitrary scale between the source scales. The solution is based on the constrained topological Generalized Area Partition (tGAP), which stores the results of a generalization process applied to the large-scale dataset, and is controlled by the objects of the medium-scale dataset, which act as constraints on the large-scale objects. The result contains the accurate geometry of the large-scale objects enriched with the generalization knowledge of the medium-scale data, stored as references in the constraint tGAP structure. The advantage of this constrained approach over the original tGAP is the higher quality of the aggregated maps. The idea was implemented with real topographic datasets from The Netherlands for the large- (1:1000) and medium-scale (1:10,000) data. The approach is expected to be equally valid for any categorical map and for other scales as well

Risk estimates of dementia by apolipoprotein E genotypes from a population-based incidence study: the Rotterdam Study

OBJECTIVES: To provide risk estimates of dementia and Alzheimer disease as a function of the apolipoprotein E (APOE) genotypes and to assess the proportion of dementia that is attributable to the APOE genotypes. DESIGN: Case-control study nested in a population-based cohort study with a mean (SD) follow-up of 2.1 (0.9) years. SETTING: General population in Rotterdam, the Netherlands. PARTICIPANTS: A total of 134 patients with incident dementia and a random sample of 997 nondemented control subjects. No participant had dementia at baseline. MAIN OUTCOME MEASURES: Odds ratios for dementia and Alzheimer disease, the fraction of dementia attributable to the APOE epsilon4 allele, and the proportion of the variance in age at the onset of dementia explained by the APOE genotypes. RESULTS: Persons with the epsilon4/4 genotype had a more than 10-fold higher risk of dementia (odds ratio, 11.2; 95% confidence interval, 3.6-35.2), and subjects with the epsilon3/4 genotype had a 1.7-fold increased risk of dementia (95% confidence interval, 1.0-2.9) as compared with persons with the epsilon3/3 genotype. The proportion of patients with dementia that is attributable to the epsilon4 allele was estimated to be 20%. The APOE genotypes explained up to 10% of the variance in age at the onset of dementia. The association between the epsilon4 allele and dementia was strongest in the youngest age category and in those with a family history of dementia. CONCLUSIONS: The APOE genotype is an important determinant of the risk of dementia. At a population level, however, other factors than the APOE genotype may play an important role in the cause of dementia

Estrogen and early-onset Alzheimer's disease

Estrogen use may be protective for Alzheimer's disease with late onset. However, the effects on early onset Alzheimer's disease are unclear. This issue was studied in a population based setting. For each female patient, a female control was matched on age (within 5 years) and place of residence. Information on estrogen use and other risk factors were, for cases (n=109) and controls (n=119), collected from the next of kin by structured interview. The strength of the association between estrogen use and early onset Alzheimer's disease was studied using conditional logistic regression with adjustment for age and education level. There was an inverse association between estrogen use and early onset Alzheimer's disease (adjusted odds ratio 0.34; 95% confidence interval 0.12-0.94). The study therefore suggests that estrogen use is beneficial to Alzheimer's disease with early onset

Homo-FRET Imaging Enables Quantification of Protein Cluster Sizes with Subcellular Resolution

Fluorescence-anisotropy-based homo-FRET detection methods can be employed to study clustering of identical proteins in cells. Here, the potential of fluorescence anisotropy microscopy for the quantitative imaging of protein clusters with subcellular resolution is investigated. Steady-state and time-resolved anisotropy detection and both one- and two-photon excitation methods are compared. The methods are evaluated on cells expressing green fluorescent protein (GFP) constructs that contain one or two FK506-binding proteins. This makes it possible to control dimerization and oligomerization of the constructs and yields the experimental relation between anisotropy and cluster size. The results show that, independent of the experimental method, the commonly made assumption of complete depolarization after a single energy transfer step is not valid here. This is due to a nonrandom relative orientation of the fluorescent proteins. Our experiments show that this relative orientation is restricted by interactions between the GFP barrels. We describe how the experimental relation between anisotropy and cluster size can be employed in quantitative cluster size imaging experiments of other GFP fusions. Experiments on glycosylphosphatidylinisotol (GPI)-anchored proteins reveal that GPI forms clusters with an average size of more than two subunits. For epidermal growth factor receptor (EGFR), we observe that ∼40% of the unstimulated receptors are present in the plasma membrane as preexisting dimers. Both examples reveal subcellular heterogeneities in cluster size and distribution

Apolipoprotein E ε 4 and the risk of dementia with stroke. A population-based investigation.

OBJECTIVE: To investigate the association between the apolipoprotein E (APOE) genotypes and dementia in patients with stroke, defined as either vascular dementia (VaD) or Alzheimer disease with cerebrovascular disease (AD with CVD). DESIGN AND SETTING: Population-based, case-control study from Rotterdam, the Netherlands, and New York City. PARTICIPANTS: A total of 187 patients with dementia and stroke were compared with 507 controls similar in age and ethnic group. MAIN OUTCOME MEASURES: The APOE allele frequencies in patients and controls; the odds ratio of dementia with stroke, VaD, and AD with CVD, adjusted for age, sex, residency, and education; and the percent attributable risk related to the APOE epsilon4 allele. RESULTS: Overall, patients with dementia and stroke had a higher APOE epsilon4 allele frequency than controls. Compared with APOE epsilon3 homozygote individuals, APOE epsilon4 homozygotes had a 7-fold increased risk of dementia with stroke (OR=6.9; 95% CI, 1.6-29.4), while APOE epsilon4 heterozygotes had nearly a 2-fold increase in risk (OR=1.8; 95% CI,

A phase 2a proof of concept clinical trial to evaluate ZPL-3893787 (ZPL-389) a potent, oral histamine H4, receptor antagonist for the treatment of moderate to severe atopic dermatitis (AD) in adults

peer reviewedIt is well documented that histamine-induced inflammation is largely mediated through the H4 receptor (H4R). T lymphocytes and keratinocytes from patients with atopic dermatitis (AD) express high levels of H4R which mediate cytokine upregulation and histamine-induced proliferation. The identification of IL-17 positive cells in psoriatic lesions, and the fact that these cells expressed a functional H4R, lends weight to its therapeutic potential in inflammatory skin diseases such as AD and psoriasis. ZPL-389 is a low nanomolar and selective H4R antagonist