Molecular signature of response to preoperative radiotherapy in locally advanced breast cancer

BACKGROUND: Radiation therapy is an indispensable part of various treatment modalities for breast cancer. Specifically, for non-inflammatory locally advanced breast cancer (LABC) patients, preoperative radiotherapy (pRT) is currently indicated as a second line therapy in the event of lack of response to neoadjuvant chemotherapy. Still approximately one third of patients fails to respond favourably to pRT. The aim of this study was to explore molecular mechanisms underlying differential response to radiotherapy (RT) to identify predictive biomarkers and potential targets for increasing radiosensitivity. METHODS: The study was based on a cohort of 134 LABC patients, treated at the Institute of Oncology and Radiology of Serbia (IORS) with pRT, without previous or concomitant systemic therapy. Baseline transcriptional profiles were established using Agilent 60 K microarray platform in a subset of 23 formalin-fixed paraffin-embedded (FFPE) LABC tumour samples of which 11 radiotherapy naïve and 3 post-radiotherapy samples passed quality control and were used for downstream analysis. Biological networks and signalling pathways underlying differential response to RT were identified using Ingenuity Pathways Analysis software. Predictive value of candidate genes in the preoperative setting was further validated by qRT-PCR in an independent subset of 60 LABC samples of which 42 had sufficient quality for data analysis, and in postoperative setting using microarray data from 344 node-negative breast cancer patients (Erasmus cohort, GSE2034 and GSE5327) treated either with surgery only (20%) or surgery with RT (80%). RESULTS: We identified 192 significantly differentially expressed genes (FDR < 0.10) between pRT-responsive and non-responsive tumours, related to regulation of cellular development, growth and proliferation, cell cycle control of chromosomal replication, glucose metabolism and NAD biosynthesis II route. APOA1, MAP3K4, and MMP14 genes were differentially expressed (FDR < 0.20) between pRT responders and non-responders in preoperative setting, while MAP3K4 was further validated as RT-specific predictive biomarker of distant metastasis free survival (HR = 2.54, [95%CI:1.42-4.55], p = 0.002) in the postoperative setting. CONCLUSIONS: This study pinpoints MAP3K4 as a putative biomarker of response to RT in both preoperative and postoperative settings and a potential target for radiosensitising combination therapy, warranting further pre-clinical studies and prospective clinical validation

Adaptive continuously variable transmission used for maintaining stationary regime of driving machine

Continuously variable transmissions (CVTs) contained in many complex systems of modern techniques can be designed as purely mechanical systems that can, thanks to their structure, do self adjustments, meaning they can change their own characteristics in order to adapt to the external parameters variations. In this way adaptive CVT can be used for automatic regulation of a system. A general approach to the dynamical description of adaptive CVT behavior as a nonholonomic, completely mechanical system is developed. For the dynamical description of the mechanical nonholonomic system, Appell`s differential equations are used. By numerically solving differential equations of motion, answers about the working stability as well as the dynamical and kinematic behavior of the observed CVT system are obtained thus proving CVT’s functional applicability as a regulator for a changeable working regime. Presented approach can be used in choosing optimal parameters for the synthesis of this type of transmissions

Influence of the teeth number on the gear module value and load capacity of gear pair in universal helical gear drives

© 2018, Serbian Academic Center. All rights reserved. The basic parameters of the universal gear drives, except the axis height, are not defined by the standard, so the manufacturers of universal gear reducers can define them in their way. Most of the manufacturers followed the parameter values of universal gear reducers of leading world producers in order to ensure their interchangeability and the better positioning of their gear units at the market. This paper deals with the analysis of the influence of the gear pair teeth number on the size of the module, as well as on the load carrying capacity of single-stage universal gear units. For defined gear ratio values, different combinations of teeth number of pinion and driven gear were selected. Further, it was made calculation of the basic geometric dimensions of the gear pair, as well as the load capacity

A Suzuki-type multivalued contraction on weak partial metric spaces and applications

Abstract Based on a recent paper of Beg and Pathak (Vietnam J. Math. 46(3):693–706, 2018), we introduce the concept of Hq+ $\mathcal{H}_{q}^{+}$-type Suzuki multivalued contraction mappings. We establish a fixed point theorem for this type of mappings in the setting of complete weak partial metric spaces. We also present an illustrated example. Moreover, we provide applications to a homotopy result and to an integral inclusion of Fredholm type. Finally, we suggest open problems for the class of 0-complete weak partial metric spaces, which is more general than complete weak partial metric spaces

Contribution of Particles to Air Pollution in Green Parks

Parks can aid in the regulation of microclimates and the improvement of air quality. They can be utilized in real-world systems to choose the best model for explaining the source of pollutant emissions, indicating the requirement for pollution concentration monitoring. Monitoring concentration trends is critical to formulating a strategy to reduce CO2 emissions and the contribution of these gasses to the greenhouse effect, as well as to curbing the rising levels of PM in the air. The research background of this study was performed in the green parks of Novi Sad, Serbia. The results are represented in terms of the quantity of the pollutants, and the correlation of the examined phenomena through statistical analysis. Aeroqual monitors with laser sensors were used to take measurements of particle pollution (PM2.5/10). The constant was confirmed by inter-comparison laboratory measurements of air-quality quantitative control. The measurement findings revealed a minor variance in concentration values for PM2.5/10 from 26&ndash;30 &mu;g/m3, which were within the allowed limits, indicating that the air was moderately clean. The linear link between particle concentrations and nitrogen dioxide in the sample was also validated using simple linear regression, as was the high influence of humidity on particle concentrations

Development of the multi-segment lumbar spine for humanoid robots

The paper presents development of multi-segment lumbar structure based on the human spine. The research is performed within the project based on development of socially acceptable robot named "SARA". Two approaches for spine realization of humanoids exist: multi-joint viscoelastic structures (5-10 joints) that have variable flexibility and structures that consist of one joint - torso/waist joint, which has low elasticity and high stiffness. We propose multi-joint flexible structure with stiff, low backlash and self-locking mechanisms that require small actuators. Based on kinematic-dynamic requirements dynamical model of robot is formed. Dynamical simulation is performed for several postures of the robot and driving torques of lumbar structure are determined. During development of the lumbar structure 16 variant solutions are considered. Developed lumbar structure consists of three equal segments, it has 6 DOFs (2 DOFs per segment) and allows movements of lateral flexion ±30° and torsion ±45°, as well as the combination of these two movements. In development phase the movements of flexion/extension are excluded, for the bending of the body forward to an angle of 45° is achieved by rotation in the hip joints. Proposed solution of the lumbar structure is characterized by self-locking of mechanisms (if for any reason actuators stop working, lumbar structure retains current posture), low backlash (high positioning accuracy and repeatability of movements), compactness, high carrying capacity and small dimensions. [Projekat Ministarstva nauke Republike Srbije, br. III44008 and by Provincial secretariat for science and technological development under contract 114-451-2116/2011

The effect of kiwifruit (Actinidia deliciosa) cysteine protease actinidin on the occludin tight junction network in T84 intestinal epithelial cells

Actinidin, a kiwifruit cysteine protease, is a marker allergen for genuine sensitization to this food allergen source. Inhalatory cysteine proteases have the capacity for disruption of tight junctions (TJs) enhancing the permeability of the bronchial epithelium. No such properties have been reported for allergenic food proteases so far. The aim was to determine the effect of actinidin on the integrity of T84 monolayers by evaluating its action on the TJ protein occludin. Immunoblot and immunofluorescence were employed for the detection of occludin protein alterations. Gene expression was evaluated by RT-PCR. Breach of occludin network was assessed by measuring transepithelial resistance, blue dextran leakage and passage of allergens from the apical to basolateral compartment. Actinidin exerted direct proteolytic cleavage of occludin; no alteration of occludin gene expression was detected. There was a reduction of occludin staining upon actinidin treatment as a consequence of its degradation and dispersion within the membrane. There was an increase in permeability of the T84 monolayer resulting in reduced transepithelial resistance, blue dextran leakage and passage of allergens actinidin and thaumatin-like protein from the apical to basolateral compartment. Opening of TJs by actinidin may increase intestinal permeability and contribute to the process of sensitization in kiwifruit allergy. (C) 2014 Elsevier Ltd. All rights reserved