The Regional Security Crisis in the Andes: Patterns of State Response

The instability, corruption, displacement of people, and violence generated by Colombia\u27s unholy trinity of narcotics traffickers, insurgents, and paramilitaries is spilling over into virtually all of northern South America and Panama. Thus, the stability and political sovereignty of the region are being compromised. And, at the same time, progress toward achieving the Free Trade Area of the Americas (FTAA) and the economic integration of the Western Hemisphere by 2005 is being severely threatened. The author outlines some of the detail and implications of the regional security crisis in the Andes and makes recommendations for U.S. civil-military involvement in the hemispheric security arena. She argues for the United States to lead in the articulation of strategic objectives, while designing a defensible and feasible policy that critical elements in North America, Central and South America, Europe, and Japan can understand and support. She specifically argues for the U.S. military to build stronger and more cooperative security relationships within the circle of affected states around Colombia.https://press.armywarcollege.edu/monographs/1836/thumbnail.jp

EMPOWER-1.0: an Efficient Model of Planktonic ecOsystems WrittEn in R

Modelling marine ecosystems requires insight and judgement when it comes to deciding upon appropriate model structure, equations and parameterisation. Many processes are relatively poorly understood and tough decisions must be made as to how to mathematically simplify the real world. Here, we present an efficient plankton modelling testbed, EMPOWER-1.0 (Efficient Model of Planktonic ecOsystems WrittEn in R), coded in the freely available language R. The testbed uses simple two-layer "slab" physics whereby a seasonally varying mixed layer which contains the planktonic marine ecosystem is positioned above a deep layer that contains only nutrient. As such, EMPOWER-1.0 provides a readily available and easy to use tool for evaluating model structure, formulations and parameterisation. The code is transparent and modular such that modifications and changes to model formulation are easily implemented allowing users to investigate and familiarise themselves with the inner workings of their models. It can be used either for preliminary model testing to set the stage for further work, e.g. coupling the ecosystem model to 1-D or 3-D physics, or for undertaking front line research in its own right. EMPOWER-1.0 also serves as an ideal teaching tool. In order to demonstrate the utility of EMPOWER-1.0, we implemented a simple nutrient–phytoplankton–zooplankton–detritus (NPZD) ecosystem model and carried out both a parameter tuning exercise and structural sensitivity analysis. Parameter tuning was demonstrated for four contrasting ocean sites, focusing on station BIOTRANS in the North Atlantic (47° N, 20° W), highlighting both the utility of undertaking a planned sensitivity analysis for this purpose, yet also the subjectivity which nevertheless surrounds the choice of which parameters to tune. Structural sensitivity tests were then performed comparing different equations for calculating daily depth-integrated photosynthesis, as well as mortality terms for both phytoplankton and zooplankton. Regarding the calculation of daily photosynthesis, for example, results indicated that the model was relatively insensitive to the choice of photosynthesis–irradiance curve, but markedly sensitive to the method of calculating light attenuation in the water column. The work highlights the utility of EMPOWER-1.0 as a means of comprehending, diagnosing and formulating equations for the dynamics of marine ecosystems

Production of trans-Neptunian binaries through chaos-assisted capture

The recent discovery of binary objects in the Kuiper-belt opens an invaluable window into past and present conditions in the trans-Neptunian part of the Solar System. For example, knowledge of how these objects formed can be used to impose constraints on planetary formation theories. We have recently proposed a binary-object formation model based on the notion of chaos-assisted capture. Here we present a more detailed analysis with calculations performed in the spatial (three-dimensional) three- and four-body Hill approximations. It is assumed that the potential binary partners are initially following heliocentric Keplerian orbits and that their relative motion becomes perturbed as these objects undergo close encounters. First, the mass, velocity, and orbital element distribu- tions which favour binary formation are identified in the circular and elliptical Hill limits. We then consider intruder scattering in the circular Hill four-body problem and find that the chaos-assisted capture mechanism is consistent with observed, apparently randomly distributed, binary mutual orbit inclinations. It also predicts asymmetric distributions of retrograde versus prograde orbits. The time-delay induced by chaos on particle transport through the Hill sphere is analogous to the formation of a resonance in a chemical reaction. Implications for binary formation rates are considered and the 'fine-tuning' problem recently identified by Noll et al. (2007) is also addressed.Comment: submitted to MNRA

Atomic Cluster Au₁₀⁺ Is a Strong Broadband Midinfrared Chromophore

We report an intense broadband midinfrared absorption band in the Au10+ cluster in a region in which only molecular vibrations would normally be expected. Observed in the infrared multiple photon dissociation spectra of Au10Ar+, Au10(N2O)+, and Au10(OCS)+, the smooth feature stretches 700–3400  cm-1 (λ=14–2.9  μm). Calculations confirm unusually low-energy allowed electronic excitations consistent with the observed spectra. In Au10(OCS)+, IR absorption throughout the band drives OCS decomposition resulting in CO loss, providing an alternative method of bond activation or breaking

Football (Soccer) as a probable cause of long-term neurological impairment and neurodegeneration: a narrative review of the debate

Football (soccer) is the most widely played sport across the globe. Due to some recent high-profile cases and epidemiological studies suggesting football can lead to neurodegeneration, scientific and public interest has been piqued. This has resulted in research into whether an association between football participation and neurodegeneration or neurological impairment is present. It has been theorised that a combination of repeated sub-concussive and concussive injuries, due to ball-heading and head collisions, may lead to neurodegeneration. However, evidence remains conflicting. Due to the popularity of the sport, and the serious conditions it has been linked to, it is important to determine whether repeated head impacts during football participation can play a causative role in neurodegenerative disease. To answer this question, a review of the current literature was carried out. Epidemiological evidence showed a higher incidence of amyotrophic lateral sclerosis amongst amateur and professional footballers and that footballers in positions that involve less contact and heading, e.g., goalkeepers lead significantly longer lives. Additionally, imaging studies reach a similar conclusion, reporting changes in brain structure, blood flow, and inflammatory markers in footballers when compared to controls. However, studies looking at an association between heading frequency and cognition show a lack of consensus on whether a higher heading exposure results in reduced cognition. Similarly, in neuropathological studies, signs of chronic traumatic encephalopathy (CTE) have been found in some former players, with contrasting studies suggesting low levels of CTE-type pathology are found in the general population, regardless of exposure to head trauma. The majority of studies suggest a link between football and neurodegenerative disease. However, the high prevalence of retrospective cohort and cross-sectional studies, often plagued by recall bias, undermine the conclusions drawn. Therefore, until larger prospective cohort studies are conducted, concrete conclusions cannot be made. However, caution can be exercised to limit head impacts

A Model Based Background Adjustment for Oligonucleotide Expression Arrays

High density oligonucleotide expression arrays are widely used in many areas of biomedical research. Affymetrix GeneChip arrays are the most popular. In the Affymetrix system, a fair amount of further pre-processing and data reduction occurs following the image processing step. Statistical procedures developed by academic groups have been successful at improving the default algorithms provided by the Affymetrix system. In this paper we present a solution to one of the pre-processing steps, background adjustment, based on a formal statistical framework. Our solution greatly improves the performance of the technology in various practical applications. Affymetrix GeneChip arrays use short oligonucleotides to probe for genes in an RNA sample. Typically each gene will be represented by 11-20 pairs of oligonucleotide probes. The first component of these pairs is referred to as a perfect match probe and is designed to hybridize only with transcripts from the intended gene (specific hybridization). However, hybridization by other sequences (non-specific hybridization) is unavoidable. Furthermore, hybridization strengths are measured by a scanner that introduces optical noise. Therefore, the observed intensities need to be adjusted to give accurate measurements of specific hybridization. One approach to adjusting is to pair each perfect match probe with a mismatch probe that is designed with the intention of measuring non-specific hybridization. The default adjustment, provided as part of the Affymetrix system, is based on the difference between perfect match and mismatch probe intensities. We have found that this approach can be improved via the use of estimators derived from a statistical model that use probe sequence information. The model is based on simple hybridization theory from molecular biology and experiments specifically designed to help develop it. A final step in the pre-processing of these arrays is to combine the 11-20 probe pair intensities, after background adjustment and normalization, for a given gene to define a measure of expression that represents the amount of the corresponding mRNA species. In this paper we illustrate the practical consequences of not adjusting appropriately for the presence of nonspecific hybridization and provide a solution based on our background adjustment procedure. Software that computes our adjustment is available as part of the Bioconductor project (http://www.bioconductor

Tools and collaborative environments for bioinformatics research

Advanced research requires intensive interaction among a multitude of actors, often possessing different expertise and usually working at a distance from each other. The field of collaborative research aims to establish suitable models and technologies to properly support these interactions. In this article, we first present the reasons for an interest of Bioinformatics in this context by also suggesting some research domains that could benefit from collaborative research. We then review the principles and some of the most relevant applications of social networking, with a special attention to networks supporting scientific collaboration, by also highlighting some critical issues, such as identification of users and standardization of formats. We then introduce some systems for collaborative document creation, including wiki systems and tools for ontology development, and review some of the most interesting biological wikis. We also review the principles of Collaborative Development Environments for software and show some examples in Bioinformatics. Finally, we present the principles and some examples of Learning Management Systems. In conclusion, we try to devise some of the goals to be achieved in the short term for the exploitation of these technologies

Modelling background intensity in Affymetrix Genechips

DNA microarrays are devices that are able, in principle, to detect and quantify the presence of specific nucleic acid sequences in complex biological mixtures. The measurement consists in detecting fluorescence signals from several spots on the microarray surface onto which different probe sequences are grafted. One of the problems of the data analysis is that the signal contains a noisy background component due to non-specific binding. This paper presents a physical model for background estimation in Affymetrix Genechips. It combines two different approaches. The first is based on the sequence composition, specifically its sequence dependent hybridization affinity. The second is based on the strong correlation of intensities from locations which are the physical neighbors of a specific spot on the chip. Both effects are incorporated in a background functional which contains 24 free parameters, fixed by minimization on a training data set. In all data analyzed the sequence specific parameters, obtained by minimization, are found to strongly correlate with empirically determined stacking free energies for RNA/DNA hybridization in solution. Moreover, there is an overall agreement with experimental background data and we show that the physics-based model proposed in this paper performs on average better than purely statistical approaches for background calculations. The model thus provides an interesting alternative method for background subtraction schemes in Affymetrix Genechips.Comment: 8 pages, 4 figure

Faster disease progression in Parkinson's disease with type 2 diabetes is not associated with increased α-synuclein, tau, amyloid-β or vascular pathology

AIMS: Growing evidence suggests a shared pathogenesis between Parkinson's disease and diabetes although the underlying mechanisms remain unknown. The aim of this study is to evaluate the effect of type 2 diabetes on Parkinson's disease progression and to correlate neuropathological findings to elucidate pathogenic mechanisms. METHODS: In this cohort study, medical records were retrospectively reviewed of cases with pathologically-confirmed Parkinson's disease with and without pre-existing type 2 diabetes. Time to disability milestones (recurrent falls, wheelchair dependence, dementia, and care home placement) and survival were compared to assess disease progression and their risk estimated using Cox hazard regression models. Correlation with pathological data was performed, including quantification of α-synuclein in key brain regions and staging of vascular, Lewy and Alzheimer's pathologies. RESULTS: Patients with PD and diabetes (male 76%; age at death 78.6 ± 6.2 years) developed earlier falls (P < 0.001), wheelchair dependence (P = 0.004), dementia (P < 0.001), care home admission (P < 0.001) and had reduced survival (P < 0.001). Predating diabetes was independently associated with a two to three-fold increase in the risk of disability and death. Neuropathological assessment did not show any differences in global or regional vascular pathology, α-synuclein load in key brain areas, staging of Lewy pathology or Alzheimer's disease pathology. CONCLUSIONS: Pre-existing type 2 diabetes contributes to faster disease progression and reduced survival in Parkinson's disease which is not driven by increased vascular, Lewy or Alzheimer's pathologies. Additional non-specific neurodegeneration related to chronic brain insulin resistance may be involved

Quality Assessment and Data Analysis for microRNA Expression Arrays

MicroRNAs are small (∼22 nt) RNAs that regulate gene expression and play important roles in both normal and disease physiology. The use of microarrays for global characterization of microRNA expression is becoming increasingly popular and has the potential to be a widely used and valuable research tool. However, microarray profiling of microRNA expression raises a number of data analytic challenges that must be addressed in order to obtain reliable results. We introduce here a universal reference microRNA reagent set as well as a series of nonhuman spiked-in synthetic microRNA controls, and demonstrate their use for quality control and between-array normalization of microRNA expression data. We also introduce diagnostic plots designed to assess and compare various normalization methods. We anticipate that the reagents and analytic approach presented here will be useful for improving the reliability of microRNA microarray experiments