Detection of early antiangiogenic effects in human colon adenocarcinoma xenografts: in vivo changes of tumor blood volume in response to experimental VEGFR tyrosine kinase inhibitor

Antiangiogenesis is emerging as efficient strategy for targeting and potentially eliminating neoplastic tumor vessels. The main goal of this study was to establish whether absolute tumor blood volume (V(b)) change could be used as an early predictor of antiangiogenesis in ectopic and orthotopic colon carcinomas. To assess therapy-induced changes of V(b), we did comparative analysis of signal intensities in tumors and muscle using steady-state magnetic resonance imaging (MRI) assisted with an intravascular paramagnetic contrast agent [gadolinium-labeled protected graft copolymer (PGC-Gd)]. Athymic mice with implanted human MV522 tumors were treated with vascular endothelial growth factor type 2 receptor tyrosine kinase inhibitor (VEGFR2-TKI) that has been shown to inhibit VEGFR2 phosphorylation and tumor growth in vivo. Animals were imaged either after a single day or after a 1-week course of treatments. The measured V(b) in ectopic tumors was 2.5 +/- 1.5% of total tissue volume 1 week after the implantation (n = 8). Two doses of VEGFR2-TKI (25 mg/kg, p.o., b.i.d.) resulted in a decrease of V(b) to 1.3 +/- 0.3%. In orthotopic tumors, the measured V(b) was initially higher (11.9 +/- 2.0%); however, VEGFR2-TKI treatment also resulted in a statistically significant decrease of V(b). The absolute V(b) was not affected in the muscle as a result of treatments. MRI measurements were corroborated by using isotope and correlative histology experiments. Our results show that steady-state MRI is highly sensitive to early antiangiogenic effects caused by small molecule drugs

k-Essence, superluminal propagation, causality and emergent geometry

The k-essence theories admit in general the superluminal propagation of the perturbations on classical backgrounds. We show that in spite of the superluminal propagation the causal paradoxes do not arise in these theories and in this respect they are not less safe than General Relativity.Comment: 34 pages, 5 figure

Genome-wide association study and scan for signatures of selection point to candidate genes for body temperature maintenance under the cold stress in Siberian cattle populations

Design of new highly productive livestock breeds, well-adapted to local climatic conditions is one of the aims of modern agriculture and breeding. The genetics underlying economically important traits in cattle are widely studied, whereas our knowledge of the genetic mechanisms of adaptation to local environments is still scarce. To address this issue for cold climates we used an integrated approach for detecting genomic intervals related to body temperature maintenance under acute cold stress. Our approach combined genome-wide association studies (GWAS) and scans for signatures of selection applied to a cattle population (Hereford and Kazakh Whiteheaded beef breeds) bred in Siberia. We utilized the GGP HD150K DNA chip containing 139,376 single nucleotide polymorphism markers

Analysis of the IHC Adaptation for the Anthropomorphic Speech Processing Systems

<p/> <p>We analyse the properties of the physiological model of the adaptive behaviour of the chemical synapse between inner hair cells (IHC) and auditory neurons. On the basis of the performed analysis, we propose equivalent structures of the model for implementation in the digital domain. The main conclusion of the analysis is that the synapse reservoir model is equivalent in its properties to the signal-dependent automatic gain-control mechanism. We plot guidelines for creation of artificial anthropomorphic algorithms, which exploit properties of the original synapse model. This paper also presents a concise description of the experiments, which prove the presence of the positive effect from the introduction of the depicted anthropomorphic algorithm into feature extraction of the automated speech recognition engine.</p