Heterogeneity in susceptibility dictates the order of epidemiological models

The fundamental models of epidemiology describe the progression of an infectious disease through a population using compartmentalized differential equations, but do not incorporate population-level heterogeneity in infection susceptibility. We show that variation strongly influences the rate of infection, while the infection process simultaneously sculpts the susceptibility distribution. These joint dynamics influence the force of infection and are, in turn, influenced by the shape of the initial variability. Intriguingly, we find that certain susceptibility distributions (the exponential and the gamma) are unchanged through the course of the outbreak, and lead naturally to power-law behavior in the force of infection; other distributions often tend towards these "eigen-distributions" through the process of contagion. The power-law behavior fundamentally alters predictions of the long-term infection rate, and suggests that first-order epidemic models that are parameterized in the exponential-like phase may systematically and significantly over-estimate the final severity of the outbreak

The Impact of Virtual Methodologies on Artificial Intelligence

Recent advances in atomic methodologies and perfect modalities do not necessarily obviate the need for replication. Given the current status of semantic algorithms, information theorists dubiously desire the deployment of superpages, which embodies the un-proven principles of cryptoanalysis. In order to accomplish this purpose, we investigate how courseware can be applied to the analysis of the Internet

CNS Remyelination and the Innate Immune System.

A misguided inflammatory response is frequently implicated in myelin damage. Particularly prominent among myelin diseases, multiple sclerosis (MS) is an autoimmune condition, with immune-mediated damage central to its etiology. Nevertheless, a robust inflammatory response is also essential for the efficient regeneration of myelin sheaths after such injury. Here, we discuss the functions of inflammation that promote remyelination, and how these have been experimentally disentangled from the pathological facets of the immune response. We focus on the contributions that resident microglia and monocyte-derived macrophages make to remyelination and compare the roles of these two populations of innate immune cells. Finally, the current literature is framed in the context of developing therapies that manipulate the innate immune response to promote remyelination in clinical myelin disease.The authors would particularly like to acknowledge the support of the UK MS Society, The Jean Shanks Foundation and MedImmune.This is the author accepted manuscript. The final version is available from Frontiers via http://dx.doi.org/10.3389/fcell.2016.0003

Blood Vessels Under the Microscope

This paper looks at blood vessels. All humans and animals have blood vessels, including your pet rabbit or dog, a whale or a giraffe! We need blood vessels to stay alive. This paper answers many questions, including what blood vessels are used for and why we need them. It looks at how and why blood vessels grow and what they look like. It also explores what happens when things go wrong with blood vessels and if blood vessels are ever bad for us. So, if you want to know how many miles of blood vessels there are in your body, learn about problems astronauts have in space, see real blood vessels through a microscope, or learn how to keep your blood vessels healthy, you are reading the right article

Radiosynthesis of [18F]-Labelled Pro-Nucleotides (ProTides).

Phosphoramidate pro-nucleotides (ProTides) have revolutionized the field of anti-viral and anti-cancer nucleoside therapy, overcoming the major limitations of nucleoside therapies and achieving clinical and commercial success. Despite the translation of ProTide technology into the clinic, there remain unresolved in vivo pharmacokinetic and pharmacodynamic questions. Positron Emission Tomography (PET) imaging using [18F]-labelled model ProTides could directly address key mechanistic questions and predict response to ProTide therapy. Here we report the first radiochemical synthesis of [18F]ProTides as novel probes for PET imaging. As a proof of concept, two chemically distinct radiolabelled ProTides have been synthesized as models of 3'- and 2'-fluorinated ProTides following different radiosynthetic approaches. The 3'-[18F]FLT ProTide was obtained via a late stage [18F]fluorination in radiochemical yields (RCY) of 15-30% (n = 5, decay-corrected from end of bombardment (EoB)), with high radiochemical purities (97%) and molar activities of 56 GBq/μmol (total synthesis time of 130 min.). The 2'-[18F]FIAU ProTide was obtained via an early stage [18F]fluorination approach with an RCY of 1-5% (n = 7, decay-corrected from EoB), with high radiochemical purities (98%) and molar activities of 53 GBq/μmol (total synthesis time of 240 min)

A Primitive Enzyme for a Primitive Cell: The Protease Required for Excystation of Giardia

AbstractProtozoan parasites of the genus Giardia are one of the earliest lineages of eukaryotic cells. To initiate infection, trophozoites emerge from a cyst in the host. Excystation is blocked by specific cysteine protease inhibitors. Using a biotinylated inhibitor, the target protease was identified and its corresponding gene cloned. The protease was localized to vesicles that release their contents just prior to excystation. The Giardia protease is the earliest known branch of the cathepsin B family. Its phylogeny confirms that the cathepsin B lineage evolved in primitive eukaryotic cells, prior to the divergence of plant and animal kingdoms, and underscores the diversity of cellular functions that this enzyme family facilitates

Employing a User-Centered Design Process for Cybersecurity Awareness in the Power Grid

In this paper, we discuss the process we are using in the design and implementation of a tool to improve the situation awareness of cyberattacks in the power grid. We provide details of the steps we have taken to date and describe the steps that still need to be accomplished. The focus of this work is to provide situation awareness of the power grid to staff from different, non-overlapping roles in an electrical transmission organization in order to facilitate an understanding of a possible occurrence of a cyberattack. Our approach follows a user-centered design process and includes determining the types of information to display, the format of the displays, and the personnel to whom the display should be shown. Additionally, there is the issue of how much help the tool can provide in the way of assessing the probability of a cyberattack given the current status of various portions of the power grid. Regardless, the ability to provide a common operating picture should enable the various groups to collaborate on a response

Editorial: Safeguarding youth from agricultural injury and illness: international experiences

[Extract] Worldwide, agriculture is among the most dangerous industries and one of the few that involves children (<18 years-of-age) in the worksite as laborers or bystanders. Children are exposed to an array of agriculture-related hazards whether working or merely being present in the farm environment. From a public health and child advocacy perspective, safeguarding these young people from preventable disease and injury is important for many reasons. The negative impacts of a childhood agricultural disease or injury range from permanent disabilities, death, family disruptions, and economic hardships including the potential loss of a sustainable family farm enterprise. At the same time, growing up in an agricultural setting can lead to independent, hardworking, successful adults, who gain a range of benefits, including skill development, family time together, improved immune response, and other protective health factors

A Pilot Study Comparing HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas by Whole Exome Sequencing.

Background. Next-generation sequencing of cancers has identified important therapeutic targets and biomarkers. The goal of this pilot study was to compare the genetic changes in a human papillomavirus- (HPV-)positive and an HPV-negative head and neck tumor. Methods. DNA was extracted from the blood and primary tumor of a patient with an HPV-positive tonsillar cancer and those of a patient with an HPV-negative oral tongue tumor. Exome enrichment was performed using the Agilent SureSelect All Exon Kit, followed by sequencing on the ABI SOLiD platform. Results. Exome sequencing revealed slightly more mutations in the HPV-negative tumor (73) in contrast to the HPV-positive tumor (58). Multiple mutations were noted in zinc finger genes (ZNF3, 10, 229, 470, 543, 616, 664, 638, 716, and 799) and mucin genes (MUC4, 6, 12, and 16). Mutations were noted in MUC12 in both tumors. Conclusions. HPV-positive HNSCC is distinct from HPV-negative disease in terms of evidence of viral infection, p16 status, and frequency of mutations. Next-generation sequencing has the potential to identify novel therapeutic targets and biomarkers in HNSCC