Inflammatory Mediators in Abdominal Aortic Aneurysms

Aortic wall dilatation in abdominal aortic aneurysms is characterized by extracellular matrix degradation together with a loss of smooth muscle cells from the aortic media. This occurs in conjunction with a marked inflammatory cell infiltration. The inflammatory cell is characteristic of the second phase of aneurysmal development–progression. It is widely accepted that usually there are three phases involved in the development of abdominal aortic aneurysms: initiation, progression and rupture. In this chapter, we present an overview of the inflammatory mediators in abdominal aortic aneurysms and intraluminal thrombus, highlighting evidence from experimental models and human disease

Trajectories of charged particles trapped in Earth's magnetic field

I outline the theory of relativistic charged-particle motion in the magnetosphere in a way suitable for undergraduate courses. I discuss particle and guiding center motion, derive the three adiabatic invariants associated with them, and present particle trajectories in a dipolar field. I provide twelve computational exercises that can be used as classroom assignments or for self-study. Two of the exercises, drift-shell bifurcation and Speiser orbits, are adapted from active magnetospheric research. The Python code provided in the supplement can be used to replicate the trajectories and can be easily extended for different field geometries.Comment: 10 pages, 7 figures. Submitted to American Journal of Physic

Biomethane Production as an Alternative Bioenergy Source from Codigesters Treating Municipal Sludge and Organic Fraction of Municipal Solid Wastes

Energy recovery potential of a mesophilic co-digester treating OFMSW and primary sludge at an integrated biomethanization plant was investigated based on feasibility study results. Since landfilling is still the main solid waste disposal method in Turkey, land scarcity will become one of the most important obstacles. Restrictions for biodegradable waste disposal to sanitary landfills in EU Landfill Directive and uncontrolled long-term contamination with gas emissions and leachate necessitate alternative management strategies due to rapid increase in MSW production. Moreover, since energy contribution from renewable resources will be required more in the future with increasing oil prices and dwindling supplies of conventional energy sources, the significance of biogas as a renewable fuel has been increased in the last decade. Results indicated that almost 93% of annual total cost can be recovered if 100% renewable energy subsidy is implemented. Besides, considering the potential revenue when replacing transport fuels, about 26 heavy good vehicles or 549 cars may be powered per year by the biogas produced from the proposed biomethanization plant (PE = 100,000; XPS = 61 g TS/PE·day; XSS-OFMSW = 50 g TS/PE·day)

Biophysical Interactions Underpin the Emergence of Information in the Genetic Code

The genetic code conceals a ‘code within the codons’, which hints at biophysical interactions between amino acids and their cognate nucleotides. Yet, research over decades has failed to corroborate systematic biophysical interactions across the code. Using molecular dynamics simulations and NMR, we have analysed interactions between the 20 standard proteinogenic amino acids and 4 RNA mononucleotides in 3 charge states. Our simulations show that 50% of amino acids bind best with their anticodonic middle base in the −1 charge state common to the backbone of RNA, while 95% of amino acids interact most strongly with at least 1 of their codonic or anticodonic bases. Preference for the cognate anticodonic middle base was greater than 99% of randomised assignments. We verify a selection of our results using NMR, and highlight challenges with both techniques for interrogating large numbers of weak interactions. Finally, we extend our simulations to a range of amino acids and dinucleotides, and corroborate similar preferences for cognate nucleotides. Despite some discrepancies between the predicted patterns and those observed in biology, the existence of weak stereochemical interactions means that random RNA sequences could template non-random peptides. This offers a compelling explanation for the emergence of genetic information in biology

Self-consistent local-equilibrium model for density profile and distribution of dissipative currents in a Hall bar under strong magnetic fields

Recent spatially resolved measurements of the electrostatic-potential variation across a Hall bar in strong magnetic fields, which revealed a clear correlation between current-carrying strips and incompressible strips expected near the edges of the Hall bar, cannot be understood on the basis of existing equilibrium theories. To explain these experiments, we generalize the Thomas-Fermi--Poisson approach for the self-consistent calculation of electrostatic potential and electron density in {\em total} thermal equilibrium to a {\em local equilibrium} theory that allows to treat finite gradients of the electrochemical potential as driving forces of currents in the presence of dissipation. A conventional conductivity model with small values of the longitudinal conductivity for integer values of the (local) Landau-level filling factor shows that, in apparent agreement with experiment, the current density is localized near incompressible strips, whose location and width in turn depend on the applied current.Comment: 9 pages, 7 figure

Isolated Hepatic Tuberculosis Presenting as Cystic-Like and Tumour-Like Mass Lesions

Hepatic tuberculosis is a rare manifestation of extra-pulmonary tuberculosis. Hepatic tuberculous lesions are especially mimicking tumour-like mass or cystic lesions in the liver and so can be misdiagnosed with several diseases. Histopathological examination of the specimen is essential in the diagnosis for hepatic tuberculosis. In this report, two cases with hepatic tuberculosis having cystic solid mass and abscess liver lesions are described

Parameter estimation for biochemical reaction networks using Wasserstein distances

We present a method for estimating parameters in stochastic models of biochemical reaction networks by fitting steady-state distributions using Wasserstein distances. We simulate a reaction network at different parameter settings and train a Gaussian process to learn the Wasserstein distance between observations and the simulator output for all parameters. We then use Bayesian optimization to find parameters minimizing this distance based on the trained Gaussian process. The effectiveness of our method is demonstrated on the three-stage model of gene expression and a genetic feedback loop for which moment-based methods are known to perform poorly. Our method is applicable to any simulator model of stochastic reaction networks, including Brownian Dynamics.Comment: 22 pages, 8 figures. Slight modifications/additions to the text; added new section (Section 4.4) and Appendi

Current Understanding and Future Research Priorities in Malignancy Associated With Inborn Errors of Immunity and DNA Repair Disorders: The Perspective of an Interdisciplinary Working Group

Patients with inborn errors of immunity or DNA repair defects are at significant risk of developing malignancy and this complication of their underlying condition represents a substantial cause of morbidity and mortality. Whilst this risk is increasingly well-recognized, our understanding of the causative mechanisms remains incomplete. Diagnosing cancer is challenging in the presence of underlying co-morbidities and frequently other inflammatory and lymphoproliferative processes. We lack a structured approach to management despite recognizing the competing challenges of poor response to therapy and increased risk of toxicity. Finally, clinicians need guidance on how to screen for malignancy in many of these predisposing immunodeficiencies. In order to begin to address these challenges, we brought together representatives of European Immunology and Pediatric Haemato-Oncology to define the current state of our knowledge and identify priorities for clinical and research development. We propose key developmental priorities which our two communities will need to work together to address, collaborating with colleagues around the world

Clinical and Serological Characterization of Orf-Induced Immunobullous Disease

Importance: Ecthyma contagiosum, or orf, is a viral zoonotic infection caused by Poxviridae. Although human orf infection is considered to follow a self-limited course, various immunological reactions may be triggered, including immunobullous diseases. In the majority of the latter cases, the antigenic target remained enigmatic. Objective: To characterize the predominant autoantigen in orf-induced immunobullous disease and further describe this clinical entity. Design, Setting, and Participants: This multicenter case series sought to provide detailed clinical, histopathological and immunological characteristics of a patient with orf-induced pemphigoid. Based on this index patient, serological analyses were conducted of 4 additional patients with previously reported orf-induced immunobullous disease. Immunoblotting with extracellular matrix and a recently established indirect immunofluorescence assay for detection of serum anti-laminin 332 IgG were performed. Exposures: The disease course and clinical characteristics of orf-induced immunobullous disease were observed. Main Outcomes and Measures: Orf-induced immunobullous disease is primarily characterized by anti-laminin 332 autoantibodies, predominant skin involvement, and a self-limiting course. The study provides further details on epidemiological, clinical, immunopathological, diagnostic, and therapeutic aspects of orf-induced immunobullous disease. Results: In all 5 patients, IgG1 and/or IgG3 autoantibodies against laminin 332 were identified. The α3, β3, and γ2 chains were recognized in 2, 4, and 1 patient(s), respectively. Conclusions and Relevance: In this case series, laminin 332, a well-known target antigen in mucous membrane pemphigoid, was a major autoantigen in orf-induced immunobullous disease, even though predominant mucosal lesions were lacking in this autoimmune blistering disease. Orf-induced anti-laminin 332 pemphigoid is proposed as distinct clinical entity

A cost effectiveness analysis of salt reduction policies to reduce coronary heart disease in four Eastern Mediterranean countries.

BACKGROUND: Coronary Heart Disease (CHD) is rising in middle income countries. Population based strategies to reduce specific CHD risk factors have an important role to play in reducing overall CHD mortality. Reducing dietary salt consumption is a potentially cost-effective way to reduce CHD events. This paper presents an economic evaluation of population based salt reduction policies in Tunisia, Syria, Palestine and Turkey. METHODS AND FINDINGS: Three policies to reduce dietary salt intake were evaluated: a health promotion campaign, labelling of food packaging and mandatory reformulation of salt content in processed food. These were evaluated separately and in combination. Estimates of the effectiveness of salt reduction on blood pressure were based on a literature review. The reduction in mortality was estimated using the IMPACT CHD model specific to that country. Cumulative population health effects were quantified as life years gained (LYG) over a 10 year time frame. The costs of each policy were estimated using evidence from comparable policies and expert opinion including public sector costs and costs to the food industry. Health care costs associated with CHDs were estimated using standardized unit costs. The total cost of implementing each policy was compared against the current baseline (no policy). All costs were calculated using 2010 PPP exchange rates. In all four countries most policies were cost saving compared with the baseline. The combination of all three policies (reducing salt consumption by 30%) resulted in estimated cost savings of $235,000,000 and 6455 LYG in Tunisia;$39,000,000 and 31674 LYG in Syria; $6,000,000 and 2682 LYG in Palestine and$1,3000,000,000 and 378439 LYG in Turkey. CONCLUSION: Decreasing dietary salt intake will reduce coronary heart disease deaths in the four countries. A comprehensive strategy of health education and food industry actions to label and reduce salt content would save both money and lives