An Improved Integrated Hash and Attributed based Encryption Model on High Dimensional Data in Cloud Environment

Cloud computing is a distributed architecture where user can store their private, public or any application software components on it. Many cloud based privacy protection solutions have been implemented, however most of them only focus on limited data resources and storage format. Data confidentiality and inefficient data access methods are the major issues which block the cloud users to store their high dimensional data. With more and more cloud based applications are being available and stored on various cloud servers, a novel multi-user based privacy protection mechanism need to design and develop to improve the privacy protection on high dimensional data. In this paper, a novel integrity algorithm with attribute based encryption model was implemented to ensure confidentiality for high dimensional data security on cloud storage. The main objective of this model is to store, transmit and retrieve the high dimensional cloud data with low computational time and high security. Experimental results show that the proposed model has high data scalability, less computational time and low memory usage compared to traditional cloud based privacy protection models

Modeling the NB-IoT transmission process with intermittent network availability

Standardized by 3GPP, Narrowband Internet-of-Thing (NB-IoT) technology operating in licensed bands is nowadays widely deployed and utilized for static deployments of IoT communications services. The recent trend to equip large complex inherently nomadic systems such as trains and ships with advanced sensory capabilities call for mobility support in NB-IoT technology. Such systems entering and leaving the NB-IoT coverage periodically could lead to synchronized behavior of sensor nodes resulting in occasional spikes in the number of sensors simultaneously accessing the NB-IoT random access channel. In this study, we develop a model capturing behavior of nomadic systems roaming between coverage of NB-IoT technology. The metrics of interest are mean message transmission delay as well as the message loss probability. Our numerical results illustrate that these metrics are mainly affected by the duration of the outage interval and fraction of time systems spends in outage conditions. At the same time, the loss and delay performance only insignificantly affected by the number of sensors implying that NB-IoT random access procedure may efficiently handle sporadic loads.acceptedVersionPeer reviewe

Proteogenomic integration reveals therapeutic targets in breast cancer xenografts

Recent advances in mass spectrometry (MS) have enabled extensive analysis of cancer proteomes. Here, we employed quantitative proteomics to profile protein expression across 24 breast cancer patient-derived xenograft (PDX) models. Integrated proteogenomic analysis shows positive correlation between expression measurements from transcriptomic and proteomic analyses; further, gene expression-based intrinsic subtypes are largely re-capitulated using non-stromal protein markers. Proteogenomic analysis also validates a number of predicted genomic targets in multiple receptor tyrosine kinases. However, several protein/phosphoprotein events such as overexpression of AKT proteins and ARAF, BRAF, HSP90AB1 phosphosites are not readily explainable by genomic analysis, suggesting that druggable translational and/or post-translational regulatory events may be uniquely diagnosed by MS. Drug treatment experiments targeting HER2 and components of the PI3K pathway supported proteogenomic response predictions in seven xenograft models. Our study demonstrates that MS-based proteomics can identify therapeutic targets and highlights the potential of PDX drug response evaluation to annotate MS-based pathway activities

FLASH Knockdown Sensitizes Cells To Fas-Mediated Apoptosis via Down-Regulation of the Anti-Apoptotic Proteins, MCL-1 and Cflip Short

FLASH (FLICE-associated huge protein or CASP8AP2) is a large multifunctional protein that is involved in many cellular processes associated with cell death and survival. It has been reported to promote apoptosis, but we show here that depletion of FLASH in HT1080 cells by siRNA interference can also accelerate the process. As shown previously, depletion of FLASH halts growth by down-regulating histone biosynthesis and arrests the cell cycle in S-phase. FLASH knockdown followed by stimulating the cells with Fas ligand or anti-Fas antibodies was found to be associated with a more rapid cleavage of PARP, accelerated activation of caspase-8 and the executioner caspase-3 and rapid progression to cellular disintegration. As is the case for most anti-apoptotic proteins, FLASH was degraded soon after the onset of apoptosis. Depletion of FLASH also resulted in the reduced intracellular levels of the anti-apoptotic proteins, MCL-1 and the short isoform of cFLIP. FLASH knockdown in HT1080 mutant cells defective in p53 did not significantly accelerate Fas mediated apoptosis indicating that the effect was dependent on functional p53. Collectively, these results suggest that under some circumstances, FLASH suppresses apoptosis

Long non-coding RNA RAMS11 promotes metastatic colorectal cancer progression

Colorectal cancer (CRC) is the most common gastrointestinal malignancy in the U.S.A. and approximately 50% of patients develop metastatic disease (mCRC). Despite our understanding of long non-coding RNAs (lncRNAs) in primary colon cancer, their role in mCRC and treatment resistance remains poorly characterized. Therefore, through transcriptome sequencing of normal, primary, and distant mCRC tissues we find 148 differentially expressed RNAs Associated with Metastasis (RAMS). We prioritize RAMS11 due to its association with poor disease-free survival and promotion of aggressive phenotypes in vitro and in vivo. A FDA-approved drug high-throughput viability assay shows that elevated RAMS11 expression increases resistance to topoisomerase inhibitors. Subsequent experiments demonstrate RAMS11-dependent recruitment of Chromobox protein 4 (CBX4) transcriptionally activates Topoisomerase II alpha (TOP2α). Overall, recent clinical trials using topoisomerase inhibitors coupled with our findings of RAMS11-dependent regulation of TOP2α supports the potential use of RAMS11 as a biomarker and therapeutic target for mCRC

Functional Annotation of ESR1 Gene Fusions in Estrogen Receptor-Positive Breast Cancer

RNA sequencing (RNA-seq) detects estrogen receptor alpha gene (ESR1) fusion transcripts in estrogen receptor-positive (ER+) breast cancer, but their role in disease pathogenesis remains unclear. We examined multiple ESR1 fusions and found that two, both identified in advanced endocrine treatment-resistant disease, encoded stable and functional fusion proteins. In both examples, ESR1-e6>YAP1 and ESR1-e6>PCDH11X, ESR1 exons 1–6 were fused in frame to C-terminal sequences from the partner gene. Functional properties include estrogen-independent growth, constitutive expression of ER target genes, and anti-estrogen resistance. Both fusions activate a metastasis-associated transcriptional program, induce cellular motility, and promote the development of lung metastasis. ESR1-e6>YAP1- and ESR1-e6>PCDH11X-induced growth remained sensitive to a CDK4/6 inhibitor, and a patient-derived xenograft (PDX) naturally expressing the ESR1-e6>YAP1 fusion was also responsive. Transcriptionally active ESR1 fusions therefore trigger both endocrine therapy resistance and metastatic progression, explaining the association with fatal disease progression, although CDK4/6 inhibitor treatment is predicted to be effective. Lei et al. show that transcriptionally active estrogen receptor gene (ESR1) fusions identified from late-stage, treatment-refractory estrogen receptor-positive (ER+) breast cancer drive pan-endocrine therapy resistance and metastatic progression. Growth of breast tumors driven by ESR1 fusions at primary and metastatic sties can be suppressed with a CDK4/6 inhibitor

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Intraoperative NIR Diffuse Optical Tomography System Based On Spatially Modulated Illumination Using The DLP4500 Evaluation Module (Conference Presentation)

We present a biomedical application of Digital Micro-mirror technologies by adapting the DLP4500 module for quasi real-time intraoperative tumor imaging. Fluorescence image guided surgery has been increasingly popular due to its ability to inform surgeons about tumor boundaries in real-time. We have extended this technique to provide 3D tomographic images of a tumor, by adapting a DLP4500 device to illuminate the surgical field with spatially modulated near-infrared (NIR) light. We combine the digital micro-mirror device (DMD) with two simultaneously triggered CMOS cameras to realize a spatial frequency domain imaging system. Spatial frequency domain imaging utilizes sinusoidally modulated illumination at different spatial frequencies and three different phases; corresponding signals are readily demodulated, and analyzed to derive a 3D fluorescence image. Our DMD device is commercially modified and equipped with high-power (5W) NIR diode laser. We present a brief discussion of data acquisition using DLP4500 module, and corrections for spatial inhomogeneity and gamma adjust in order to create linear/desired sinusoidal illumination of NIR light. We discuss results from a tissue phantom study and in-vivo experiments