Multi-Omic Data Interpretation to Repurpose Subtype Specific Drug Candidates for Breast Cancer

Triple-negative breast cancer (TNBC), which is largely synonymous with the basal-like molecular subtype, is the 5th leading cause of cancer deaths for women in the United States. The overall prognosis for TNBC patients remains poor given that few treatment options exist; including targeted therapies (not FDA approved), and multi-agent chemotherapy as standard-of-care treatment. TNBC like other complex diseases is governed by the perturbations of the complex interaction networks thereby elucidating the underlying molecular mechanisms of this disease in the context of network principles, which have the potential to identify targets for drug development. Here, we present an integrated “omics” approach based on the use of transcriptome and interactome data to identify dynamic/active protein-protein interaction networks (PPINs) in TNBC patients. We have identified three highly connected modules, EED, DHX9, and AURKA, which are extremely activated in TNBC tumors compared to both normal tissues and other breast cancer subtypes. Based on the functional analyses, we propose that these modules are potential drivers of proliferation and, as such, should be considered candidate molecular targets for drug development or drug repositioning in TNBC. Consistent with this argument, we repurposed steroids, anti-inflammatory agents, anti-infective agents, cardiovascular agents for patients with basal-like breast cancer. Finally, we have performed essential metabolite analysis on personalized genome-scale metabolic models and found that metabolites such as sphingosine-1-phosphate and cholesterol-sulfate have utmost importance in TNBC tumor growth

On Kähler-Norden-Codazzi golden structures on pseudo-Riemannian manifolds

In this paper, we consider a pseudo-Riemannian manifold equipped with a Kähler-Norden-Codazzi golden structure. For such a manifold, we study curvature properties. Also, we define special connections of the first type and of the second type on the manifold, which preserve the associated twin Norden golden metric and satisfy some special conditions and present some results concerning them. © 2018 World Scientific Publishing Company

First record of Cassida pusilla Waltl, 1835 (Coleoptera: Chrysomelidae: Cassidinae) in Turkey

[No abstract available

Stress-Strain Behaviour of Structural Lightweight Concrete under Confinement

In this study, stress-strain behavior of structural lightweight concrete is studied under unconfined and confined conditions. To this end, the use of naturally occurring perlite material as lightweight aggregate and cement replacement material is considered. Although there are several studies on the confinement effects on normal weight concrete, there is lack of data on the confinement behavior attained for structural lightweight concrete by spiral or stirrup reinforcement. In order to evaluate the performances of structural lightweight concrete and normal weight concrete in a reliable manner, an experimental study is conducted. Through the experimental study on cylinder specimens that are unconfined and confined in different percentages by spiral reinforcement, the elastic and inelastic, namely post-peak behavior of structural lightweight concrete is recorded by the use of displacementcontrolled testing machine. The results indicate that concrete produced from perlite as lightweight aggregate as well as through the use of cement replacement material provide significant energy absorption in the presence of spiral reinforcement

Alkali reactivity of mortars containing chert and incorporating moderate-calcium fly ash

This paper reports the results of an experimental program, which aimed to investigate the alkali reactivity of chert and the effect of a moderate-calcium fly ash on the alkali-silica reaction. To determine the expansions, mortar bars were cast and tested in accordance with ASTM C1260. Mortar aggregate was replaced by chert, in controlled amounts, to find out the pessimum limit, if any. To evaluate the degree of cracking, sonic pulse velocity measurements and petrographic analysis were carried out on the cracked bars and on the thin sections taken from these bars, respectively. In the next series of tests, limestone and chert were blended together as mortar aggregate and cement was replaced by different dosages of fly ash to examine the changes in the mortar bar expansion as well as in the chemistry of reaction products. Microstructural observations were done on polished sections using a scanning electron microscope, equipped with energy dispersive X-ray analysis. The results showed that the chert used in this investigation had a pessimum proportion in the range of 5-15%. Sufficient fly-ash additions suppressed the expansion caused by chert. The study also revealed out that as the CaO/Na2Oeq of alkali-silica gel increased, the expansivity of the gel decreased

Pozzolanic activity of clinoptilolite: A comparative study with silica fume, fly ash and a non-zeolitic natural pozzolan

WOS: 000274869600006Pozzolanic activity of clinoptilolite, the most common natural zeolite mineral, was studied in comparison to silica fume, fly ash and a non-zeolitic natural pozzolan. Chemical, mineralogical and physical characterizations of the materials were considered in comparative evaluations. Pozzolanic activity of the natural zeolite was evaluated with various test methods including electrical conductivity of lime-pozzolan suspensions; and free lime content, compressive strength and pore size distribution of hardened lime-pozzolan pastes. The results showed that the clinoptilolite possessed a high lime-pozzolan reactivity that was comparable to silica fume and was higher than fly ash and a non-zeolitic natural pozzolan. The high reactivity of the clinoptilolite is attributable to its specific surface area and reactive SiO(2) content. Relatively poor strength contribution of clinoptilolite in spite of high pozzolanic activity can be attributable to larger pore size distribution of the hardened zeolite-lime product compared to the lime-fly ash system. (C) 2009 Elsevier Ltd. All rights reserved.Scientific and Technological Research Council of Turkey [104M393]This study was funded by The Scientific and Technological Research Council of Turkey under Project Number: 104M393. The instrumental analyses in this study were carried out in Middle East Technical University Central Laboratory. Acknowledgment is given to Emeritus Professor P. Kumar Mehta from the Civil and Environmental Engineering Department at the University of California, Berkeley, for his helpful comments during the investigation