Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain

SummaryStem cell factor (SCF) is overexpressed by neurons following brain injury as well as by glioma cells; however, its role in gliomagenesis remains unclear. Here, we demonstrate that SCF directly activates brain microvascular endothelial cells (ECs) in vitro and induces a potent angiogenic response in vivo. Primary human gliomas express SCF in a grade-dependent manner and induce normal neurons to express SCF in brain regions infiltrated by glioma cells, areas that colocalize with prominent angiogenesis. Downregulation of SCF inhibits tumor-mediated angiogenesis and glioma growth in vivo, whereas overexpression of SCF is associated with shorter survival in patients with malignant gliomas. Thus, the SCF/c-Kit pathway plays an important role in tumor- and normal host cell-induced angiogenesis within the brain

Motion in classical field theories and the foundations of the self-force problem

This article serves as a pedagogical introduction to the problem of motion in classical field theories. The primary focus is on self-interaction: How does an object's own field affect its motion? General laws governing the self-force and self-torque are derived using simple, non-perturbative arguments. The relevant concepts are developed gradually by considering motion in a series of increasingly complicated theories. Newtonian gravity is discussed first, then Klein-Gordon theory, electromagnetism, and finally general relativity. Linear and angular momenta as well as centers of mass are defined in each of these cases. Multipole expansions for the force and torque are then derived to all orders for arbitrarily self-interacting extended objects. These expansions are found to be structurally identical to the laws of motion satisfied by extended test bodies, except that all relevant fields are replaced by effective versions which exclude the self-fields in a particular sense. Regularization methods traditionally associated with self-interacting point particles arise as straightforward perturbative limits of these (more fundamental) results. Additionally, generic mechanisms are discussed which dynamically shift --- i.e., renormalize --- the apparent multipole moments associated with self-interacting extended bodies. Although this is primarily a synthesis of earlier work, several new results and interpretations are included as well.Comment: 68 pages, 1 figur

From Input to Intake: Researching Learner Cognition

The distinction between input, what the teachers say to their learners, and intake, what the learners hear, has been recognised in research into second language acquisition at least since Corder (1967). The distinction is important because language development does not result from the input to which learners are exposed but what the learners take in. If a teacher in a class focussing on the past simple says “Harry and Megan cooked a curry last weekend,” the input that the learners are exposed to is “Harry and Megan cooked a curry last weekend.” However, if a learner hears “Harry and Megan cook a curry last weekend” then this sentence, in all its non-standard grammaticality, is the intake and this episode is unlikely to contribute to the learner’s command of the past tense. If, for example, researchers were interested in identifying the number of instances of the past tense needed for learners to acquire this tense, research that counted the number of times the teacher used the past tense will only help us to understand the acquisition process if there is a systematic relationship between what the teacher says, the input, and what the learner hears, the intake. However, the conceptual distinction between input and intake in second language acquisition (SLA) has been poorly operationalized and much research treats input as a straightforward proxy for intake. This article explores the relationship between input and intake in order to identify strategies for researching language development that are based on a more solid understanding of the connections between input and intake

Comparative effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors and human glucagon-like peptide-1 (GLP-1) analogue as add-on therapies to sulphonylurea among diabetes patients in the Asia-Pacific region: a systematic review

The prevalence of diabetes mellitus is rising globally, and it induces a substantial public health burden to the healthcare systems. Its optimal control is one of the most significant challenges faced by physicians and policy-makers. Whereas some of the established oral hypoglycaemic drug classes like biguanide, sulphonylureas, thiazolidinediones have been extensively used, the newer agents like dipeptidyl peptidase-4 (DPP-4) inhibitors and the human glucagon-like peptide-1 (GLP-1) analogues have recently emerged as suitable options due to their similar efficacy and favorable side effect profiles. These agents are widely recognized alternatives to the traditional oral hypoglycaemic agents or insulin, especially in conditions where they are contraindicated or unacceptable to patients. Many studies which evaluated their clinical effects, either alone or as add-on agents, were conducted in Western countries. There exist few reviews on their effectiveness in the Asia-Pacific region. The purpose of this systematic review is to address the comparative effectiveness of these new classes of medications as add-on therapies to sulphonylurea drugs among diabetic patients in the Asia-Pacific countries. We conducted a thorough literature search of the MEDLINE and EMBASE from the inception of these databases to August 2013, supplemented by an additional manual search using reference lists from research studies, meta-analyses and review articles as retrieved by the electronic databases. A total of nine randomized controlled trials were identified and described in this article. It was found that DPP-4 inhibitors and GLP-1 analogues were in general effective as add-on therapies to existing sulphonylurea therapies, achieving HbA1c reductions by a magnitude of 0.59–0.90% and 0.77–1.62%, respectively. Few adverse events including hypoglycaemic attacks were reported. Therefore, these two new drug classes represent novel therapies with great potential to be major therapeutic options. Future larger-scale research should be conducted among other Asia-Pacific region to evaluate their efficacy in other ethnic groups

Large scale analytic calculations in quantum field theories

We present a survey on the mathematical structure of zero- and single scale quantities and the associated calculation methods and function spaces in higher order perturbative calculations in relativistic renormalizable quantum field theories.Comment: 25 pages Latex, 1 style fil

Parasites, drugs and captivity: blastocystis-microbiome associations in captive water voles

(1) Background: Blastocystis is a microbial eukaryote inhabiting the gastrointestinal tract of a broad range of animals including humans. Several studies have shown that the organism is associated with specific microbial profiles and bacterial taxa that have been deemed beneficial to intestinal and overall health. Nonetheless, these studies are focused almost exclusively on humans, while there is no similar information on other animals. (2) Methods: Using a combination of conventional PCR, cloning and sequencing, we investigated presence of Blastocystis along with Giardia and Cryptosporidium in 16 captive water voles sampled twice from a wildlife park. We also characterised their bacterial gut communities. (3) Results: Overall, alpha and beta diversities between water voles with and without Blastocystis did not differ significantly. Differences were noted only on individual taxa with Treponema and Kineothrix being significantly reduced in Blastocystis positive water voles. Grouping according to antiprotozoal treatment and presence of other protists did not reveal any differences in the bacterial community composition either. (4) Conclusion: Unlike human investigations, Blastocystis does not seem to be associated with specific gut microbial profiles in water vole

Genetic correlations between diabetes and glaucoma: an analysis of continuous and dichotomous phenotypes

Purpose: A genetic correlation is the proportion of phenotypic variance between traits that is shared on a genetic basis. Here we explore genetic correlations between diabetes- and glaucoma-related traits.Design: Cross-sectional study.Methods: We assembled genome-wide association study summary statistics from European-derived participants regarding diabetes-related traits like fasting blood sugar (FBS) and type 2 diabetes (T2D) and glaucoma-related traits (intraocular pressure (IOP), central corneal thickness (CCT), corneal hysteresis (CH), corneal resistance factor (CRF), cup-disc ratio (CDR), and primary open-angle glaucoma (POAG)). We included data from the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database, the UK Biobank and the International Glaucoma Genetics Consortium. We calculated genetic correlation (rg) between traits using linkage disequilibrium score regression. We also calculated genetic correlations between IOP, CCT and selected diabetes-related traits based on individual level phenotype data in two Northern European population-based samples using pedigree information and Sequential Oligogenic Linkage Analysis Routines (SOLAR).Results: Overall, there was little rg between diabetes- and glaucoma-related traits. Specifically, we found a non-significant negative correlation between T2D and POAG (rg=-0.14; p=0.16). Using SOLAR, the genetic correlations between measured IOP, CCT, FBS, fasting insulin and hemoglobin A1c, were null. In contrast, genetic correlations between IOP and POAG (rg ≥0.45; p≤3.0E-04) and between CDR and POAG were high (rg =0.57; p=2.8E-10). However, genetic correlations between corneal properties (CCT, CRF and CH) and POAG were low (rg range: -0.18 - 0.11) and non-significant (p≥0.07).Conclusion: These analyses suggest there is limited genetic correlation between diabetes- and glaucoma-related traits

The Potential Economic Value of a Trypanosoma cruzi (Chagas Disease) Vaccine in Latin America

The substantial burden of Chagas disease, especially in Latin America, and the limitations of currently available treatment and control strategies have motivated the development of a Trypanosoma cruzi (T. cruzi) vaccine. Evaluating a vaccine's potential economic value early in its development can answer important questions while the vaccine's key characteristics (e.g., vaccine efficacy targets, price points, and target population) can still be altered. This can assist vaccine scientists, manufacturers, policy makers, and other decision makers in the development and implementation of the vaccine. We developed a computational economic model to determine the cost-effectiveness of introducing a T. cruzi vaccine in Latin America. Our results showed vaccination to be very cost-effective, in many cases providing both cost savings and health benefits, even at low infection risk and vaccine efficacy. Moreover, our study suggests that a vaccine may actually “pay for itself”, as even a relatively higher priced vaccine will generate net cost savings for a purchaser (e.g., a country's ministry of health). These findings support continued investments in and efforts toward the development of a human T. cruzi vaccine