Physical Context Detection using Wearable Wireless Sensor Networks

This paper presents the architecture of a wearable sensor network and a Hidden Markov Model (HMM) processingframework for stochastic identification of body postures andphysical contexts. The key idea is to collect multi-modal sensor data from strategically placed wireless sensors over a human subject’s body segments, and to process that using HMM in order to identify the subject’s instantaneous physical context. The key contribution of the proposed multi-modal approach is a significant extension of traditional uni-modal accelerometry in which only the individual body segment movements, without their relative proximities and orientation modalities, is used for physical context identification. Through real-life experiments with body mounted sensors it is demonstrated that while the unimodal accelerometry can be used for differentiating activityintensive postures such as walking and running, they are not effective for identification and differentiation between lowactivity postures such as sitting, standing, lying down, etc. In the proposed system, three sensor modalities namely acceleration, relative proximity and orientation are used for context identification through Hidden Markov Model (HMM) based stochastic processing. Controlled experiments using human subjects are carried out for evaluating the accuracy of the HMMidentified postures compared to a naïve threshold based mechanism over different human subjects

IoT Privacy and Security: Challenges and Solutions

Privacy and security are among the significant challenges of the Internet of Things (IoT). Improper device updates, lack of efficient and robust security protocols, user unawareness, and famous active device monitoring are among the challenges that IoT is facing. In this work, we are exploring the background of IoT systems and security measures, and identifying (a) different security and privacy issues, (b) approaches used to secure the components of IoT-based environments and systems, (c) existing security solutions, and (d) the best privacy models necessary and suitable for different layers of IoT driven applications. In this work, we proposed a new IoT layered model: generic and stretched with the privacy and security components and layers identification. The proposed cloud/edge supported IoT system is implemented and evaluated. The lower layer represented by the IoT nodes generated from the Amazon Web Service (AWS) as Virtual Machines. The middle layer (edge) implemented as a Raspberry Pi 4 hardware kit with support of the Greengrass Edge Environment in AWS. We used the cloud-enabled IoT environment in AWS to implement the top layer (the cloud). The security protocols and critical management sessions were between each of these layers to ensure the privacy of the users’ information. We implemented security certificates to allow data transfer between the layers of the proposed cloud/edge enabled IoT model. Not only is the proposed system model eliminating possible security vulnerabilities, but it also can be used along with the best security techniques to countermeasure the cybersecurity threats facing each one of the layers; cloud, edge, and IoT

A Critical Study of Ijtihad Methodologies: Jurisprudential Approaches to Al-Massaalih Al-Murssalah

This research is concerned with the study of the issue of al-massaalih al-mursalah (public interests,. It explores how ijtihad scholars dealt with the issue, showing their ijtihad attempts, as based on masslahah, and showing their underlying foundations and rules. The research approach inVol.ves the identification of the methodological rules, foundations and branches that were adopted by the jurisprudential schools and that manifest scholars' ijtihad approaches to dealing with the issue of al-masslahah al-mursalah. It is an inductive approach, analytical of jurisprudential scholars' masslahah-oriented ijtihad and of their intended outcome-related views. Each scholar's ijtihad methodology in approaching al-masslahah al-mursalah is examined separately. One of the important conclusions is that almasslahah al-mursalah is based on Shari'ah's general foundations and universal rules due to its association with religion and Shari'ah purposes regarding the realization of public interests. Therefore, recognized Muslim religious leaders and scholars from credible Muslim schools of thought agree on taking public interests into consideration in related ijtihad issues. Apparently, differences in that regard are a matter of terminology rather than reality or substance. As for recommendations, the research calls for giving more attention to ijtihad legislation sources in general, and al-massalih al-mursalah in particular, at the colleges of Shari'ah foundations. It also calls for the teaching of practical examples in methodological foundations as applied by ijtihad scholars, rather than concentration on terminology matters

MicroRNA-223 is a novel negative regulator of HSP90B1 in CLL

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: MicroRNAs are known to inhibit gene expression by binding to the 3'UTR of the target transcript. Downregulation of miR-223 has been recently reported to have prognostic significance in CLL. However, there is no evidence of the pathogenetic mechanism of this miRNA in CLL patients. [Methods]: By applying next-generation sequencing techniques we have detected a common polymorphism (rs2307842), in 24% of CLL patients, which disrupts the binding site for miR-223 in HSP90B1 3'UTR. We investigated whether miR-223 directly targets HSP90B1 through luciferase assays and ectopic expression of miR-223. Quantitative real-time polymerase chain reaction and western blot were used to determine HSP90B1 expression in CLL patients. The relationship between rs2307842 status, HSP90B1 expression and clinico-biological data were assessed. [Results]: HSP90B1 is a direct target for miR-223 by interaction with the putative miR-223 binding site. The analysis in paired samples (CD19+ fraction cell and non-CD19+ fraction cell) showed that the presence of rs2307842 and IGHV unmutated genes determined HSP90B1 overexpression in B lymphocytes from CLL patients. These results were confirmed at the protein level by western blot. Of note, HSP90B1 overexpression was independently predictive of shorter time to the first therapy in CLL patients. By contrast, the presence of rs2307842 was not related to the outcome. [Conclusions]: HSP90B1 is a direct target gene of miR-223. Our results provide a plausible explanation of why CLL patients harboring miR-223 downregulation are associated with a poor outcome, pointing out HSP90B1 as a new pathogenic mechanism in CLL and a promising therapeutic target.This work was partially supported by grants from the Spanish Fondo de Investigaciones Sanitarias FIS 09/01543 and PI12/00281, Proyectos de Investigación del SACYL 355/A/09, COST Action EuGESMA (BM0801), Fundación Manuel Solórzano, Obra Social Banca Cívica (Caja Burgos), Fundación Española de Hematología y Hemoterapia (FEHH) and by a grant (RD12/0036/0069) from the Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness & European Regional Development Fund (ERDF) “Una manera de hacer Europa” (Innocampus). The research leading to these results has received funding from the European Union Seventh Framework Programme [FP7/2007-2013] under Grant Agreement n°306242-NGS-PTL. MHS is fully supported by an Ayuda predoctoral de la Junta de Castilla y Leon by the Fondo Social Europeo. ME Sarasquete is supported by Contrato Miguel Servet (CP13/00080).Peer Reviewe

Stroma-Mediated Resistance to S63845 and Venetoclax through MCL-1 and BCL-2 Expression Changes Induced by miR-193b-3p and miR-21-5p Dysregulation in Multiple Myeloma.

BH3-mimetics targeting anti-apoptotic proteins such as MCL-1 (S63845) or BCL-2 (venetoclax) are currently being evaluated as effective therapies for the treatment of multiple myeloma (MM). Interleukin 6, produced by mesenchymal stromal cells (MSCs), has been shown to modify the expression of anti-apoptotic proteins and their interaction with the pro-apoptotic BIM protein in MM cells. In this study, we assess the efficacy of S63845 and venetoclax in MM cells in direct co-culture with MSCs derived from MM patients (pMSCs) to identify additional mechanisms involved in the stroma-induced resistance to these agents. MicroRNAs miR-193b-3p and miR-21-5p emerged among the top deregulated miRNAs in myeloma cells when directly co-cultured with pMSCs, and we show their contribution to changes in MCL-1 and BCL-2 protein expression and in the activity of S63845 and venetoclax. Additionally, direct contact with pMSCs under S63845 and/or venetoclax treatment modifies myeloma cell dependence on different BCL-2 family anti-apoptotic proteins in relation to BIM, making myeloma cells more dependent on the non-targeted anti-apoptotic protein or BCL-XL. Finally, we show a potent effect of the combination of S63845 and venetoclax even in the presence of pMSCs, which supports this combinatorial approach for the treatment of MM

Expression of p53 protein isoforms predicts survival in patients with multiple myeloma

Loss and/or mutation of the TP53 gene are associated with short survival in multiple myeloma, but the p53 landscape goes far beyond. At least 12 p53 protein isoforms have been identified as a result of a combination of alternative splicing, alternative promoters and/or alternative transcription site starts, which are grouped as α, β, γ, from transactivation domain (TA), long, and short isoforms. Nowadays, there are no studies evaluating the expression of p53 isoforms and its clinical relevance in multiple myeloma (MM). We used capillary nanoimmunoassay to quantify the expression of p53 protein isoforms in CD138‐purified samples from 156 patients with newly diagnosed MM who were treated as part of the PETHEMA/GEM2012 clinical trial and investigated their prognostic impact. Quantitative real‐time polymerase chain reaction was used to corroborate the results at RNA levels. Low and high levels of expression of short and TAp53β/γ isoforms, respectively, were associated with adverse prognosis in MM patients. Multivariate Cox models identified high levels of TAp53β/γ (hazard ratio [HR], 4.49; p < .001) and high‐risk cytogenetics (HR, 2.69; p < .001) as independent prognostic factors associated with shorter time to progression. The current cytogenetic‐risk classification was notably improved when expression levels of p53 protein isoforms were incorporated, whereby high‐risk MM expressing high levels of short isoforms had significantly longer survival than high‐risk patients with low levels of these isoforms. This is the first study that demonstrates the prognostic value of p53 isoforms in MM patients, providing new insights on the role of p53 protein dysregulation in MM biology

MicroRNA-223 is a novel negative regulator of HSP90B1 in CLL

Background MicroRNAs are known to inhibit gene expression by binding to the 3′UTR of the target transcript. Downregulation of miR-223 has been recently reported to have prognostic significance in CLL. However, there is no evidence of the pathogenetic mechanism of this miRNA in CLL patients. Methods By applying next-generation sequencing techniques we have detected a common polymorphism (rs2307842), in 24% of CLL patients, which disrupts the binding site for miR-223 in HSP90B1 3′UTR. We investigated whether miR-223 directly targets HSP90B1 through luciferase assays and ectopic expression of miR-223. Quantitative real-time polymerase chain reaction and western blot were used to determine HSP90B1 expression in CLL patients. The relationship between rs2307842 status,HSP90B1 expression and clinico-biological data were assessed. Results HSP90B1 is a direct target for miR-223 by interaction with the putative miR-223 binding site. The analysis in paired samples (CD19+ fraction cell and non-CD19+ fraction cell) showed that the presence of rs2307842 and IGHV unmutated genes determined HSP90B1 overexpression in B lymphocytes from CLL patients. These results were confirmed at the protein level by western blot. Of note, HSP90B1 overexpression was independently predictive of shorter time to the first therapy in CLL patients. By contrast, the presence of rs2307842 was not related to the outcome. Conclusions HSP90B1 is a direct target gene of miR-223. Our results provide a plausible explanation of why CLL patients harboring miR-223 downregulation are associated with a poor outcome, pointing out HSP90B1 as a new pathogenic mechanism in CLL and a promising therapeutic target. Keywords Chronic lymphocytic leukemia MicroRNAs Next-generation sequencingEuropean Commision (EC). Funding FP7/SP1/HEALTH. Project Code: 30624