One-pot synthesis and negative ion mass spectrometric investigation of a densely functionalized cinnoline, 3-amino-5,7,8-trichloro-6-hydroxycinnoline-4-carbonitrile

Known densely substituted 3-amino-5,7,8-trichloro-6-hydroxycinnoline-4-carbonitrile was synthesized using a new synthetic protocol involving chloranil and malonitrile via quinone methide formation. This one-pot synthesis occurs under base mediated conditions in a polar medium. The method involves condensation of excess malononitrile with chloranil in ethanol at reflux to 2-(2,4,5-trichloro-3-hydroxy-6-oxocyclohexa-2,4-dien-1-ylidene) malononitrile. This is an atom efficient, simple and effective procedure for the preparation of a highly substituted cinnoline that can serve as a relay to antimalarial prototypes

Classical and semi-classical energy conditions

The standard energy conditions of classical general relativity are (mostly) linear in the stress-energy tensor, and have clear physical interpretations in terms of geodesic focussing, but suffer the significant drawback that they are often violated by semi-classical quantum effects. In contrast, it is possible to develop non-standard energy conditions that are intrinsically non-linear in the stress-energy tensor, and which exhibit much better well-controlled behaviour when semi-classical quantum effects are introduced, at the cost of a less direct applicability to geodesic focussing. In this article we will first review the standard energy conditions and their various limitations. (Including the connection to the Hawking--Ellis type I, II, III, and IV classification of stress-energy tensors). We shall then turn to the averaged, nonlinear, and semi-classical energy conditions, and see how much can be done once semi-classical quantum effects are included.Comment: V1: 25 pages. Draft chapter, on which the related chapter of the book "Wormholes, Warp Drives and Energy Conditions" (to be published by Springer), will be based. V2: typos fixed. V3: small typo fixe

Purpurogallin-A heme binding component of oak galls

Recently, it has been shown that Purpurogallin (PPG), an orange benztropolone constituent of oak galls and its derivative, CU-CPT22, can compete with the binding of the specific lipoprotein ligand to toll-like receptors (TLRs), which are type I transmembrane proteins. These recognize pathogen-derived macromolecules that play a key role in the innate immune system. This system provides an attractive target for the treatment of various immune disorders. Notably, PPG also interacts with various metals and its mode of action against HIV in vitro may involve inhibition of metal containing integrases. In the current study, an optimised synthesis of PPG is presented together with its gas phase behaviour (probed by mass spectrometry) as well as its redox behaviour with porphyrins such as heme. This interaction may also explain its effects at metal containing integrases within HIV in vitro as well as its action during processing of iron complexes within Plasmodia. This compound could serve as a novel prototype for the synthesis of novel redox active antimalarials

Interim heterogeneity changes measured using entropy texture features on T2- weighted MRI at 3.0 T predict pathological response to neoadjuvant chemotherapy in primary breast cancer

Objectives: This study investigated whether interim changes in hetereogeneity (measured using entropy features) on magnetic resonance images (MRI) were associated with pathological residual cancer burden (RCB) at final surgery in patients receiving neoadjuvant chemotherapy (NAC) for primary breast cancer.Methods: Institutional review board approval was waived for this retrospective study of 88 consenting women (age:30-79). Scanning was performed on a 3.0T MRI scanner prior to NAC (baseline) and after 2-3 cycles of treatment (interim). Entropy was derived from the grey-level co-occurrence matrix, on slice-matched baseline/interim T2- weighted images. Response, assessed using RCB score on surgically resected specimens, was compared statistically with entropy/heterogeneity changes and ROC analysis performed. Prediction of pCR within each tumour immunophenotype was evaluated.Results: Mean entropy percent differences between examinations, by response category, were: pCR:32.8%, RCB-I:10.5%, RCB-II:9.7% and RCB-III:3.0%. Prediction of ultimate pCR from coarse entropy changes between baseline/interim MRI across all lesions yielded 85.2% accuracy (area under ROC curve:0.845). Excellent sensitivity/specificity was obtained for pCR prediction within each immunophenotype: ER+: 100%/100%; HER2+: 83.3%/95.7%, TNBC: 87.5%/80.0%.Conclusions: Lesion T2 heterogeneity changes are associated with response to NAC using RCB scores, particularly for pCR, and can be useful in prediction across all immunophenotypes with good diagnostic accuracy

Obesity-Related Oxidative Stress: the Impact of Physical Activity and Diet Manipulation

Obesity-related oxidative stress, the imbalance between pro-oxidants and antioxidants (e.g., nitric oxide), has been linked to metabolic and cardiovascular disease, including endothelial dysfunction and atherosclerosis. Reactive oxygen species (ROS) are essential for physiological functions including gene expression, cellular growth, infection defense, and modulating endothelial function. However, elevated ROS and/or diminished antioxidant capacity leading to oxidative stress can lead to dysfunction. Physical activity also results in an acute state of oxidative stress. However, it is likely that chronic physical activity provides a stimulus for favorable oxidative adaptations and enhanced physiological performance and physical health, although distinct responses between aerobic and anaerobic activities warrant further investigation. Studies support the benefits of dietary modification as well as exercise interventions in alleviating oxidative stress susceptibility. Since obese individuals tend to demonstrate elevated markers of oxidative stress, the implications for this population are significant. Therefore, in this review our aim is to discuss (i) the role of oxidative stress and inflammation as associated with obesity-related diseases, (ii) the potential concerns and benefits of exercise-mediated oxidative stress, and (iii) the advantageous role of dietary modification, including acute or chronic caloric restriction and vitamin D supplementation

Comparison of breast cancer survival in two populations: Ardabil, Iran and British Columbia, Canada

<p>Abstract</p> <p>Background</p> <p>Patterns in survival can provide information about the burden and severity of cancer, help uncover gaps in systemic policy and program delivery, and support the planning of enhanced cancer control systems. The aim of this paper is to describe the one-year survival rates for breast cancer in two populations using population-based cancer registries: Ardabil, Iran, and British Columbia (BC), Canada.</p> <p>Methods</p> <p>All newly diagnosed cases of female breast cancer were identified in the Ardabil cancer registry from 2003 to 2005 and the BC cancer registry for 2003. The International Classification of Disease for Oncology (ICDO) was used for coding cancer morphology and topography. Survival time was determined from cancer diagnosis to death. Age-specific one-year survival rates, relative survival rates and weighted standard errors were calculated using life-tables for each country.</p> <p>Results</p> <p>Breast cancer patients in BC had greater one-year survival rates than patients in Ardabil overall and for each age group under 60.</p> <p>Conclusion</p> <p>These findings support the need for breast cancer screening programs (including regular clinical breast examinations and mammography), public education and awareness regarding early detection of breast cancer, and education of health care providers.</p

A Semantic Problem Solving Environment for Integrative Parasite Research: Identification of Intervention Targets for Trypanosoma cruzi

Effective research in parasite biology requires analyzing experimental lab data in the context of constantly expanding public data resources. Integrating lab data with public resources is particularly difficult for biologists who may not possess significant computational skills to acquire and process heterogeneous data stored at different locations. Therefore, we develop a semantic problem solving environment (SPSE) that allows parasitologists to query their lab data integrated with public resources using ontologies. An ontology specifies a common vocabulary and formal relationships among the terms that describe an organism, and experimental data and processes in this case. SPSE supports capturing and querying provenance information, which is metadata on the experimental processes and data recorded for reproducibility, and includes a visual query-processing tool to formulate complex queries without learning the query language syntax. We demonstrate the significance of SPSE in identifying gene knockout targets for T. cruzi. The overall goal of SPSE is to help researchers discover new or existing knowledge that is implicitly present in the data but not always easily detected. Results demonstrate improved usefulness of SPSE over existing lab systems and approaches, and support for complex query design that is otherwise difficult to achieve without the knowledge of query language syntax