Evolutionary algorithm for content-based image search

Content-based image retrieval systems attempt to provide a means of searching for images in large repositories without using any information other than that contained in the image itself, usually in the form of low-level descriptors. Since these descriptors do not accurately represent the semantics of the image, evaluating the perceptual similarity between two images based only on them is not a trivial task. This paper describes an effective method for image recovery based on evolutionary computing techniques. The results are compared with those obtained by the classical approach of the movement of the query point and the rescheduling of the axes and by a technique based on self-organizing maps, showing a remarkably higher performance in the repositories

OpenDR: An Open Toolkit for Enabling High Performance, Low Footprint Deep Learning for Robotics

Existing Deep Learning (DL) frameworks typically do not provide ready-to-use solutions for robotics, where very specific learning, reasoning, and embodiment problems exist. Their relatively steep learning curve and the different methodologies employed by DL compared to traditional approaches, along with the high complexity of DL models, which often leads to the need of employing specialized hardware accelerators, further increase the effort and cost needed to employ DL models in robotics. Also, most of the existing DL methods follow a static inference paradigm, as inherited by the traditional computer vision pipelines, ignoring active perception, which can be employed to actively interact with the environment in order to increase perception accuracy. In this paper, we present the Open Deep Learning Toolkit for Robotics (OpenDR). OpenDR aims at developing an open, non-proprietary, efficient, and modular toolkit that can be easily used by robotics companies and research institutions to efficiently develop and deploy AI and cognition technologies to robotics applications, providing a solid step towards addressing the aforementioned challenges. We also detail the design choices, along with an abstract interface that was created to overcome these challenges. This interface can describe various robotic tasks, spanning beyond traditional DL cognition and inference, as known by existing frameworks, incorporating openness, homogeneity and robotics-oriented perception e.g., through active perception, as its core design principles.acceptedVersionPeer reviewe

Current perspectives on bone metastases in castrate-resistant prostate cancer

Prostate cancer is the most frequent noncutaneous cancer occurring in men. On average, men with localized prostate cancer have a high 10-year survival rate, and many can be cured. However, men with metastatic castrate-resistant prostate cancer have incurable disease with poor survival despite intensive therapy. This unmet need has led to recent advances in therapy aimed at treating bone metastases resulting from prostate cancer. The bone microenvironment lends itself to metastases in castrate-resistant prostate cancer, as a result of complex interactions between the microenvironment and tumor cells. The development of 223radium dichloride (Ra-223) to treat symptomatic bone metastases has improved survival in men with metastatic castrate-resistant prostate cancer. Moreover, Ra-223 may have effects on the tumor microenvironment that enhance its activity. Ra-223 treatment has been shown to prolong survival, and its effects on the immune system are under investigation. Because prostate cancer affects a sizable portion of the adult male population, understanding how it metastasizes to bone is an important step in advancing therapy. Clinical trials that are underway should yield new information on whether Ra-223 synergizes effectively with immunotherapy agents and whether Ra-223 has enhancing effects on the immune system in patients with prostate cancer

A comparison of the radiosensitisation ability of 22 different element metal oxide nanoparticles using clinical megavoltage X-rays

Background: A wide range of nanoparticles (NPs), composed of different elements and their compounds, are being developed by several groups as possible radiosensitisers, with some already in clinical trials. However, no systematic experimental survey of the clinical X-ray radiosensitising potential of different element nanoparticles has been made. Here, we directly compare the irradiation-induced (10 Gy of 6-MV X-ray photon) production of hydroxyl radicals, superoxide anion radicals and singlet oxygen in aqueous solutions of the following metal oxide nanoparticles: Al2O3, SiO2, Sc2O3, TiO2, V2O5, Cr2O3, MnO2, Fe3O4, CoO, NiO, CuO, ZnO, ZrO2, MoO3, Nd2O3, Sm2O3, Eu2O3, Gd2O3, Tb4O7, Dy2O3, Er2O3 and HfO2. We also examine DNA damage due to these NPs in unirradiated and irradiated conditions. Results: Without any X-rays, several NPs produced more radicals than water alone. Thus, V2O5 NPs produced around 5-times more hydroxyl radicals and superoxide radicals. MnO2 NPs produced around 10-times more superoxide anions and Tb4O7 produced around 3-times more singlet oxygen. Lanthanides produce fewer hydroxyl radicals than water. Following irradiation, V2O5 NPs produced nearly 10-times more hydroxyl radicals than water. Changes in radical concentrations were determined by subtracting unirradiated values from irradiated values. These were then compared with irradiation-induced changes in water only. Irradiation-specific increases in hydroxyl radical were seen with most NPs, but these were only significantly above the values of water for V2O5, while the Lanthanides showed irradiation-specific decreases in hydroxyl radical, compared to water. Only TiO2 showed a trend of irradiation-specific increase in superoxides, while V2O5, MnO2, CoO, CuO, MoO3 and Tb4O7 all demonstrated significant irradiation-specific decreases in superoxide, compared to water. No irradiation-specific increases in singlet oxygen were seen, but V2O5, NiO, CuO, MoO3 and the lanthanides demonstrated irradiation-specific decreases in singlet oxygen, compared to water. MoO3 and CuO produced DNA damage in the absence of radiation, while the highest irradiation-specific DNA damage was observed with CuO. In contrast, MnO2, Fe3O4 and CoO were slightly protective against irradiation-induced DNA damage. Conclusions: Beyond identifying promising metal oxide NP radiosensitisers and radioprotectors, our broad comparisons reveal unexpected differences that suggest the surface chemistry of NP radiosensitisers is an important criterion for their success

Tight junctions and the modulation of barrier function in disease

Tight junctions create a paracellular barrier in epithelial and endothelial cells protecting them from the external environment. Two different classes of integral membrane proteins constitute the tight junction strands in epithelial cells and endothelial cells, occludin and members of the claudin protein family. In addition, cytoplasmic scaffolding molecules associated with these junctions regulate diverse physiological processes like proliferation, cell polarity and regulated diffusion. In many diseases, disruption of this regulated barrier occurs. This review will briefly describe the molecular composition of the tight junctions and then present evidence of the link between tight junction dysfunction and disease

Identification of a candidate prognostic gene signature by transcriptome analysis of matched pre-and post-treatment prostatic biopsies from patients with advanced prostate cancer

Background: Although chemotherapy for prostate cancer (PCa) can improve patient survival, some tumours are chemo-resistant. Tumour molecular profiles may help identify the mechanisms of drug action and identify potential prognostic biomarkers. We performed in vivo transcriptome profiling of pre- and post-treatment prostatic biopsies from patients with advanced hormone-naive prostate cancer treated with docetaxel chemotherapy and androgen deprivation therapy (ADT) with an aim to identify the mechanisms of drug action and identify prognostic biomarkers. Methods: RNA sequencing (RNA-Seq) was performed on biopsies from four patients before and ~22 weeks after docetaxel and ADT initiation. Gene fusion products and differentially-regulated genes between treatment pairs were identified using TopHat and pathway enrichment analyses undertaken. Publically available datasets were interrogated to perform survival analyses on the gene signatures identified using cBioportal. Results: A number of genomic rearrangements were identified including the TMPRSS2/ERG fusion and 3 novel gene fusions involving the ETS family of transcription factors in patients, both pre and post chemotherapy. In total, gene expression analyses showed differential expression of at least 2 fold in 575 genes in post-chemotherapy biopsies. Of these, pathway analyses identified a panel of 7 genes (ADAM7, FAM72B, BUB1B, CCNB1, CCNB2, TTK, CDK1), including a cell cycle-related geneset, that were differentially-regulated following treatment with docetaxel and ADT. Using cBioportal to interrogate the MSKCC-Prostate Oncogenome Project dataset we observed a statistically-significant reduction in disease-free survival of patients with tumours exhibiting alterations in gene expression of the above panel of 7 genes (p = 0.015). Conclusions: Here we report on the first “real-time” in vivo RNA-Seq-based transcriptome analysis of clinical PCa from pre- and post-treatment TRUSS-guided biopsies of patients treated with docetaxel chemotherapy plus ADT. We identify a chemotherapy-driven PCa transcriptome profile which includes the down-regulation of important positive regulators of cell cycle progression. A 7 gene signature biomarker panel has also been identified in high-risk prostate cancer patients to be of prognostic value. Future prospective study is warranted to evaluate the clinical value of this panel

Targeting cell cycle and hormone receptor pathways in cancer

The cyclin/cyclin-dependent kinase (CDK)/retinoblastoma (RB)-axis is a critical modulator of cell cycle entry and is aberrant in many human cancers. New nodes of therapeutic intervention are needed that can delay or combat the onset of malignancies. The antitumor properties and mechanistic functions of PD-0332991 (PD; a potent and selective CDK4/6 inhibitor) were investigated using human prostate cancer (PCa) models and primary tumors. PD significantly impaired the capacity of PCa cells to proliferate by promoting a robust G1-arrest. Accordingly, key regulators of the G1-S cell cycle transition were modulated including G1 cyclins D, E and A. Subsequent investigation demonstrated the ability of PD to function in the presence of existing hormone-based regimens and to cooperate with ionizing radiation to further suppress cellular growth. Importantly, it was determined that PD is a critical mediator of PD action. The anti-proliferative impact of CDK4/6 inhibition was revealed through reduced proliferation and delayed growth using PCa cell xenografts. Finally, first-in-field effects of PD on proliferation were observed in primary human prostatectomy tumor tissue explants. This study shows that selective CDK4/6 inhibition, using PD either as a single-agent or in combination, hinders key proliferative pathways necessary for disease progression and that RB status is a critical prognostic determinant for therapeutic efficacy. Combined, these pre-clinical findings identify selective targeting of CDK4/6 as a bona fide therapeutic target in both early stage and advanced PCa and underscore the benefit of personalized medicine to enhance treatment response.C E S Comstock, M A Augello, J F Goodwin, R de Leeuw, M J Schiewer, W F Ostrander Jr, R A Burkhart, A K McClendon, P A McCue, E J Trabulsi, C D Lallas, L G Gomella, M M Centenera, J R Brody, L M Butler, W D Tilley and K E Knudse

Analysis of Emergence of Quinolone-Resistant Gonococci in Greece by Combined Use of Neisseria gonorrhoeae Multiantigen Sequence Typing and Multilocus Sequence Typing▿†§

The prevalence of quinolone-resistant Neisseria gonorrhoeae (QRNG) in Greece remained low from 1997 to 2003 but increased dramatically from 11% to 56% between 2004 and 2007. N. gonorrhoeae multiantigen sequence typing (NG-MAST) and multilocus sequence typing (MLST) were used to investigate trends in quinolone resistance from 1997 to 2007 and explore the origins of the recent increase in QRNG. We characterized 295 QRNG isolates from the study period and 233 quinolone-susceptible (QS) gonococci from 2004 and 2005, when the rapid increase in QRNG occurred. From 1997 to 1999, an outbreak of QRNG was due to the dissemination of isolates of serovar Arst that belonged to two closely related genotypes. Few QRNG isolates, of diverse genotypes, were present between 2001 and 2003, whereas the sharp increase in QRNG from 2004 onwards was due to the appearance of serovar Bropyst isolates of several major NG-MAST sequence type (STs) that previously had not been identified in Greece. These isolates were shown by MLST to be variants of a single multiply antibiotic-resistant QRNG strain (ST1901) that appeared in Greece and rapidly diversified into 31 NG-MAST STs. There were no isolates of MLST ST1901 or any of the 31 NG-MAST STs among QS isolates from 2004 and 2005 or among 8 representatives of multiresistant but quinolone-susceptible serovar Bropyst isolates circulating in Greece during the 1990s, supporting the view that the recent increase in QRNG was due to importation of a QRNG strain(s) of MLST ST1901 into Greece. Recently, multiresistant QRNG isolates of ST1901 with reduced susceptibility to the newer cephalosporins have appeared in Greece