Multiple myeloma (MM), the second most common hematologic malignancy, is characterized by the clonal expansion of plasma cells. Despite dramatic improvements in patients′ survival over the past decade due to advances in therapy exploiting novel molecular targets (immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies), the treatment of relapsed and refractory disease remains challenging. Recent studies confirmed complex, dynamic, and heterogeneous genomic alterations without unifying gene mutations in MM patients. In the current review, we survey recent therapeutic strategies, as well as molecular profiling data on MM, with emphasis on relapsed and refractory cases. A critical appraisal of novel findings and of their potential therapeutic implications will be discussed in detail, along with the author’s own experiences/views.

Discoidin domain receptors DDR1 and DDR2 are the only receptor tyrosine kinases that bind to and signal in response to collagen. In cancer, DDRs have been shown to play a key role in mediating the crosstalk between tumor cells and the stromal collagen matrix. Because prostate cancer (PCa) preferentially metastasizes to bone, a collagen-rich microenvironment, we set out to investigate the role of DDR1 in intraosseous growth of PC3 cells, a human PCa cell line that expresses DDR1 but not DDR2. PC3 cells were engineered to express short hairpin RNAs (shRNAs) against DDR1, or a scrambled shRNA as a control. These cells were inoculated into the tibiae of male SCID mice, and then bone response and intraosseous tumor growth evaluated by X-ray and histomorphometry. Whereas no differences were observed in bone response (osteolytic lesions), downregulation of DDR1 in PC3 cells was associated with a significant increase in intraosseous tumor growth when compared to control PC3 cells (P Citation Format: R. Daniel Bonfil, Anjum Sohail, Semir Vranic, Daniel S. Oliveira, Dongping Shi, Wei Chen, Hyejeong Jang, Allen D. Saliganan, Benjamin D. Wasinski, Hyeong-Reh C. Kim, Rafael A. Fridman. Discoidin domain receptor 1 (DDR1): A potential suppressor of prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1070.

Dayton Peace Agreement (DPA) has resulted in asymmetric decentralization in Bosnia and Herzegovina (BiH) in all aspects: political, administrative and fiscal. Decentralization driven by non-economic reasons is rather usual concept, and often the main reasons are political, ethnical or overall country stability. Decentralization model implemented in BiH became huge obstacle not only in reaching efficiency in provision of public services, but also to further economic development. While the purpose of DPA was to stop armed conflict, and while valuable back in time, there is no excuse to keep these solutions for more than 20 years. This paper aims to provide deep insight into experience of selected comparative countries where non-economic reasons initiated decentralization. In addition, it aims to identify patterns and features of administrative, fiscal and political arrangements that perform better in the environment similar to BiH. Analysis of the experience in developed countries identified different models in organizing ethnically divided societies and establishing different forms of cooperation between sub-national government units to increase efficiency. Transitional countries experience shows mixed results in terms of positive effects of decentralization on overall efficiency and citizens' well-being, but there is valuable experience and number of features, which may improve municipal efficiency in BiH as well. Having in mind very limited literature focused on specific BiH context as well as the need to improve efficiency at local community level, this paper takes an important first step in this direction by providing a systematic review of decentralization design in countries that had similar challenges as BiH. The focus of comparative analysis is on the administrative decentralization (territorial organization and responsibility designation), political decentralization (addressing democratic principles) and fiscal independency. Paper has identified certain mechanisms that do not require any or require minor changes in core legislation introduced by DPA. These primarily include activation of cooperation mechanisms already allowed by law as well as improving system of revenue and grant allocation. Democratization still did not reached proper level as mechanisms introduced by DPA do not address rights of minorities, and this has to be changed. Improving municipal efficiency in BiH by applying experience of developed and transitional countries therefore may range from better cooperation according to the existing laws, to substantive changes of legislation.

Alopecia areata (AA) is a non-scarring inflammatory disease of the hair follicle. Although it usually presents as asymptomatic localized hair loss, it is a disese of very broad spectrum. Alopecia universalis (AU) is an uncommon form of AA that involves the loss of all haed and body hair and is estimated to account approximately 5% of all alopecia cases [1]. The cause of disease is unknown, although there is evidence to suggest that the link between lymphocytic infiltration of the follicle and the disruption of the hair follicle cycle in AA may be provided by a combination of factors, including cytokine release, cytotoxic T-cell activity, and apoptosis [2,3]. It is also considered that a disequilibrium in the production of cytokines, with a relative excess of proinflammatory and Th1 types, vs. anti-inflammatory cytokines may be involved in the persistence of AA lesions, as shown in human scalp biopsies [4]. The immune response presented in AU is associated with aberrant lesional expression of interferon-gamma (IFN-γ), interleukin-2 (IL-2) and IL-1β, and overexpression of ICAM-1 and MHC molecules on hair follicle keratinocytes and dermal papilla cells [5].

Secondary prevention of ischemic stroke: overview of updated guidelines Abstract. It is widely stated that stroke is one of the most common diseases and the leading cause of severe disability in adults. Secondary stroke prevention is based on drug treatment, risk factor control as well as interventional procedures such as carotid artery revascularization or percutaneous device closure of a patent foramen ovale in cryptogenic stroke patients younger than 60 years.

This paper presents a large-scale simulator study on driver adherence to recommendationsgiven by driver support systems, specifically eco-driving support and navigation support.123 participants too ...

Single hidden layer feed forward neural networks are widely used for various practical problems. However, the training process for determining synaptic weights of such neural networks can be computationally very expensive. In this paper we propose a new learning algorithm for learning the synaptic weights of the single hidden layer feedforward neural networks in order to reduce the learning time. We propose combining the upgraded bat algorithm with the extreme learning machine. The proposed approach reduces the number of evaluations needed to train a neural network and efficiently finds optimal input weights and the hidden biases. The proposed algorithm was tested on standard benchmark classification problems and functions and compared with other approaches from literature. The results have shown that our approach produces a satisfactory performance in almost all cases and that it can obtains solutions much faster than the traditional learning algorithms.

This paper presents a nonlinear flatness-based control (FBC) approach for a full-order doubly fed induction generator (DFIG) in the wind turbine system. Flat outputs of the DFIG and the FBC controller are derived using differential flatness theory. The proposed approach ensures an efficient decoupled control for both active and reactive powers of the DFIG. Also, it provides a smooth trajectory tracking in the start-up and the rest to rest modes without any saturation. Therefore, the system satisfactory operates at a variable speed of the rotor with an effective active/reactive power tracking. The variable rotor speed represents a perturbation caused by changes in the wind speed or different wind energy capacity. The requirements on the active and the reactive power are converted into system variables using a high-level reference trajectory generator (HLRTG). The effectiveness of the proposed system is verified by simulations.

The aim of this research is to finalize implementation of new method and algorithm of Collaborative and Non-Collaborative Dynamic Path Prediction for Mobile objects Collision Detection with Dynamic Obstacles in 2D and 3D Space. The method is based human behavior in collision detection with vehicles in real-life natural environment. Advantages of proposed method are full decentralization of the system, minimizing network traffic and simplifying inclusion of additional agents in the system. The proposed method is inspired by nature and implemented in mobile robotics. The method decreases uncertainty and increases predictability in collision detection with dynamic obstacles. Method allows implementation of fully functional algorithm which is tested in experimental environment and shows excellent results both in collaborative mode using exchange of coordinates as well as non-collaborative mode using OpenCV library for computer imaging and mobile objects tracking. The proposed algorithm is named Sliding Holt algorithm. This research paper should be considered as a part of series of research papers published earlier.