A phase Ib study combining the second-generation DNA hypomethylating agent (DHA) guadecitabine (SGI-110) and ipilimumab in patients with metastatic melanoma: The NIBIT-M4 Study

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Using Semantic Web technologies in the development of data warehouses: A systematic mapping

The exploration and use of Semantic Web technologies have attracted considerable attention from researchers examining data warehouse (DW) development. However, the impact of this research and the maturity level of its results are still unclear. The objective of this study is to examine recently published research articles that take into account the use of Semantic Web technologies in the DW arena with the intention of summarizing their results, classifying their contributions to the field according to publication type, evaluating the maturity level of the results, and identifying future research challenges. Three main conclusions were derived from this study: (a) there is a major technological gap that inhibits the wide adoption of Semantic Web technologies in the business domain;(b) there is limited evidence that the results of the analyzed studies are applicable and transferable to industrial use; and (c) interest in researching the relationship between DWs and Semantic Web has decreased because new paradigms, such as linked open data, have attracted the interest of researchers.This study was supported by the Universidad de La Frontera, Chile, PROY. DI15-0020. Universidad de la Frontera, Chile, Grant Numbers: DI15-0020 and DI17-0043

Decitabine immunosensitizes human gliomas to NY-ESO-1 specific T lymphocyte targeting through the Fas/Fas Ligand pathway

<p>Abstract</p> <p>Background</p> <p>The lack of effective treatments for gliomas makes them a significant health problem and highlights the need for the development of novel and innovative treatment approaches. Immunotherapy is an appealing strategy because of the potential ability for immune cells to traffic to and destroy infiltrating tumor cells. However, the absence of well-characterized, highly immunogenic tumor-rejection antigens (TRA) in gliomas has limited the implementation of targeted immune-based therapies.</p> <p>Methods</p> <p>We hypothesized that treatment with the demethylating agent, decitabine, would upregulate the expression of TRA on tumor cells, thereby facilitating enhanced surveillance by TRA-specific T cells.</p> <p>Results and Discussion</p> <p>Treatment of human glioma cells with decitabine increased the expression of NY-ESO-1 and other well characterized cancer testes antigens. The upregulation of NY-ESO-1 made these tumors susceptible to NY-ESO-1-specific T-cell recognition and lysis. Interestingly, decitabine treatment of T98 glioma cells also sensitized them to Fas-dependent apoptosis with an agonistic antibody, while a Fas blocking antibody could largely prevent the enhanced functional recognition by NY-ESO-1 specific T cells. Thus, decitabine treatment transformed a non-immunogenic glioma cell into an immunogenic target that was efficiently recognized by NY-ESO-1--specific T cells.</p> <p>Conclusions</p> <p>Such data supports the hypothesis that agents which alter epigenetic cellular processes may "immunosensitize" tumor cells to tumor-specific T cell-mediated lysis.</p

Crude Oil-Degradation and Plasmid Profile of Nitrifying Bacteria Isolated from Oil-Impacted Mangrove Sediment in the Niger Delta of Nigeria

The crude oil degradability and plasmid profile of autotrophic nitrifying bacteria, Nitrosomonas and Nitrobacter species, isolated from mangrove sediment in the Niger Delta of Nigeria were studied. The effects of temperature, pH and optical density on the utilization of different carbon sources by the bacteria were also investigated. Results showed that nitrifying bacteria could utilize kerosene, diesel oil, jet fuel and engine oil as carbon sources. None utilized hexane and xylene but moderate growth was observed in benzene, phenol and toluene. However, their ability to utilized crude oil varied both in rates of utilization and in growth profiles. Mixed culture of the isolates degrades 52 % of crude oil introduced into the medium followed by Nitrosomonas sp. with 40 % degradation. The least was Nitrobacter sp. with 20 % degradation. The ability of the autotrophs to degrade crude oil was found to be plasmid-mediated through curing experiment and electrophoresis. The size of the plasmid involved was estimated to be 23 kb. The high crude oil utilization of the mixed culture implies that nitrifying bacteria isolated from contaminated ecosystem are excellent crude oil degraders and can be harnessed for bioremediation purposes

Empirical estimates of prostate cancer overdiagnosis by age and prostate-specific antigen

Background: Prostate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing by age and baseline PSA.Methods: Estimates of the effects of age on overdiagnosis were based on population based incidence data from the US Surveillance, Epidemiology and End Results database. To investigate the relationship between PSA and overdiagnosis, we used two separate cohorts subject to PSA testing in clinical trials (n = 1,577 and n = 1,197) and a population-based cohort of Swedish men not subject to PSA-screening followed for 25 years (n = 1,162).Results: If PSA testing had been restricted to younger men, the number of excess cases associated with the introduction of PSA in the US would have been reduced by 85%, 68% and 42% for age cut-offs of 60, 65 and 70, respectively. The risk that a man with screen-detected cancer at age 60 would not subsequently lead to prostate cancer morbidity or mortality decreased exponentially as PSA approached conventional biopsy thresholds. For PSAs below 1 ng/ml, the risk of a positive biopsy is 65 (95% CI 18.2, 72.9) times greater than subsequent prostate cancer mortality.Conclusions: Prostate cancer overdiagnosis has a strong relationship to age and PSA level. Restricting screening in men over 60 to those with PSA above median (>1 ng/ml) and screening men over 70 only in selected circumstances would importantly reduce overdiagnosis and change the ratio of benefits to harms of PSA-screening

Bending continuous structures with SMAs: a novel robotic fish design

In this paper, we describe our research on bio-inspired locomotion systems using deformable structures and smart materials, concretely shape memory alloys (SMAs). These types of materials allow us to explore the possibility of building motor-less and gear-less robots. A swimming underwater fish-like robot has been developed whose movements are generated using SMAs. These actuators are suitable for bending the continuous backbone of the fish, which in turn causes a change in the curvature of the body. This type of structural arrangement is inspired by fish red muscles, which are mainly recruited during steady swimming for the bending of a flexible but nearly incompressible structure such as the fishbone. This paper reviews the design process of these bio-inspired structures, from the motivations and physiological inspiration to the mechatronics design, control and simulations, leading to actual experimental trials and results. The focus of this work is to present the mechanisms by which standard swimming patterns can be reproduced with the proposed design. Moreover, the performance of the SMA-based actuators’ control in terms of actuation speed and position accuracy is also addressed

A Screen for Genes Expressed in the Olfactory Organs of Drosophila melanogaster Identifies Genes Involved in Olfactory Behaviour

BACKGROUND: For insects the sense of smell and associated olfactory-driven behaviours are essential for survival. Insects detect odorants with families of olfactory receptor proteins that are very different to those of mammals, and there are likely to be other unique genes and genetic pathways involved in the function and development of the insect olfactory system. METHODOLOGY/PRINCIPAL FINDINGS: We have performed a genetic screen of a set of 505 Drosophila melanogaster gene trap insertion lines to identify novel genes expressed in the adult olfactory organs. We identified 16 lines with expression in the olfactory organs, many of which exhibited expression of the trapped genes in olfactory receptor neurons. Phenotypic analysis showed that six of the lines have decreased olfactory responses in a behavioural assay, and for one of these we showed that precise excision of the P element reverts the phenotype to wild type, confirming a role for the trapped gene in olfaction. To confirm the identity of the genes trapped in the lines we performed molecular analysis of some of the insertion sites. While for many lines the reported insertion sites were correct, we also demonstrated that for a number of lines the reported location of the element was incorrect, and in three lines there were in fact two pGT element insertions. CONCLUSIONS/SIGNIFICANCE: We identified 16 new genes expressed in the Drosophila olfactory organs, the majority in neurons, and for several of the gene trap lines demonstrated a defect in olfactory-driven behaviour. Further characterisation of these genes and their roles in olfactory system function and development will increase our understanding of how the insect olfactory system has evolved to perform the same essential function to that of mammals, but using very different molecular genetic mechanisms

Enhanced production of multi-strange hadrons in high-multiplicity proton-proton collisions

At sufficiently high temperature and energy density, nuclear matter undergoes a transition to a phase in which quarks and gluons are not confined: the quark-gluon plasma (QGP)(1). Such an exotic state of strongly interacting quantum chromodynamics matter is produced in the laboratory in heavy nuclei high-energy collisions, where an enhanced production of strange hadrons is observed(2-6). Strangeness enhancement, originally proposed as a signature of QGP formation in nuclear collisions(7), is more pronounced for multi-strange baryons. Several effects typical of heavy-ion phenomenology have been observed in high-multiplicity proton-proton (pp) collisions(8,9), but the enhanced production of multi-strange particles has not been reported so far. Here we present the first observation of strangeness enhancement in high-multiplicity proton-proton collisions. We find that the integrated yields of strange and multi-strange particles, relative to pions, increases significantly with the event charged-particle multiplicity. The measurements are in remarkable agreement with the p-Pb collision results(10,11), indicating that the phenomenon is related to the final system created in the collision. In high-multiplicity events strangeness production reaches values similar to those observed in Pb-Pb collisions, where a QGP is formed.Peer reviewe