Neutron Shielding Optimization Studies

The IsoDAR sterile-neutrino search calls for a high neutron flux from a 60 MeV proton beam striking a beryllium target, that flood a sleeve of highly-enriched 7Li, the beta-decay of the resulting 8Li giving the desired neutrinos for the veryshort-baseline experiment. The target is placed very close to an existing large neutrino detector; all such existing or planned detectors are deep underground, in low-background environments. It is necessary to design a shielding enclosure to prevent neutrons from causing unacceptable activation of the environment. GEANT4 is being used to study neutron attenuation, and optimising the layers of shielding material to minimize thickness. Materials being studied include iron and two new types of concrete developed by Jefferson Laboratory, one very light with shredded plastic aggregate, the other with high quantities of boron. Initial studies indicate that a total shielding thickness of 1.5 meters produces the required attenuation factor, further studies may allow decrease in thickness. Minimising it will reduce the amount of cavity excavation needed to house the target system in confined underground spaces

High Power Cyclotrons for the Neutrino Experiments DAEδALUS and IsoDAR

DAEδALUS (Decay At rest Experiment for δcp At a Laboratory for Underground Science) has been proposed to measure the value of the CP violating phase delta through the oscillation of low energy muon anti-neutrinos to electron antineutrinos. With a single large detector, three accelerators at different distances enable the oscillation to be measured with sufficient accuracy. We have proposed the superconducting multi-megawatt DAEδALUS Supercinducting Ring Cyclotron (DSRC) as the means of producing the 800 MeV 12 mA protons required, through the acceleration of H2+, ions with highly efficient stripping extraction. The DSRC comprises twin ion sources and injector cyclotrons, followed by a booster. The injector cyclotron can also be used for a separate experiment, IsoDAR (Isotope Decay At Rest) in which low energy protons produce Lithium 8, and thus a very pure electron antineutrino source which can be used to measure, or rule out, short range oscillation to a sterile neutrino. We describe recent developments in the designs of the injector and the booster, and the prospects for the two experiments

Why Healthcare and Well-being Researchers should Become Developers: A Case Study Using Co-Creation Methodology

Wearable technologies increase the ability to track different parameters related to health and well-being. As the variety and amount of data sources grow, a better understanding of health-related data can be obtained through research on data fusion. Outcomes can either be validated by end users when results are finalized or throughout the design and development process of mobile health applications. This chapter addresses the co-creation methodology applied for the creation of a mobile health application, called Vire, and the backend, called Synergy, to serve personal data to the mobile health application. Synergy provides an interface for the research team to interact with participants and visualizes parameters relevant to the study. Modern frameworks and platforms, such as React Native and Meteor, are used to facilitate the adaptiveness and functionality required for the co-creation of Vire. The chapter concludes by addressing the findings from the study with 26 participants

Lung metastases share common immune features regardless of primary tumor origin

BACKGROUND: Only certain disseminated cells are able to grow in secondary organs to create a metastatic tumor. Under the hypothesis that the immune microenvironment of the host tissue may play an important role in this process, we have categorized metastatic samples based on their immune features. METHODS: Gene expression data of metastatic samples (n=374) from four secondary sites (brain, bone, liver and lung) were used to characterize samples based on their immune and stromal infiltration using gene signatures and cell quantification tools. A clustering analysis was done that separated metastatic samples into three different immune categories: high, medium and low. RESULTS: Significant differences were found between the immune profiles of samples metastasizing in distinct organs. Metastases in lung showed a higher immunogenic score than metastases in brain, liver or bone, regardless of their primary site of origin. Also, they preferentially clustered in the high immune group. Samples in this cluster exhibited a clear inflammatory phenotype, higher levels of immune infiltrate, overexpression of programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) pathways and upregulation of genes predicting clinical response to programmed cell death protein 1 (PD-1) blockade (T-cell inflammatory signature). A decision tree algorithm was used to select CD74 as a biomarker that identify samples belonging to this high-immune subtype of metastases, having specificity of 0.96 and sensitivity of 1. CONCLUSIONS: We have found a group of lung-enriched metastases showing an inflammatory phenotype susceptible to be treated with immunotherapy

Recombinant antibody against Trypanosoma cruzi from patients with chronic Chagas heart disease recognizes mammalian nervous system.

Background: To deeply understand the role of antibodies in the context of Trypanosoma cruzi infection, we decided to characterize A2R1, a parasite antibody selected from single-chain variable fragment (scFv) phage display libraries constructed from B cells of chronic Chagas heart disease patients. Methods: Immunoblot, ELISA, cytometry, immunofluorescence and immunohistochemical assays were used to characterize A2R1 reactivity. To identify the antibody target, we performed an immunoprecipitation and two-dimensional electrophoresis coupled to mass spectrometry and confirmed A2R1 specific interaction by producing the antigen in different expression systems. Based on these data, we carried out a comparative in silico analysis of the protein target_s orthologues, focusing mainly on post-translational modifications. Findings: A2R1 recognizes a parasite protein of ~50 kDa present in all life cycle stages of T. cruzi, as well as in other members of the kinetoplastid family, showing a defined immunofluorescence labeling pattern consistent with the cytoskeleton. A2R1 binds to tubulin, but this interaction relies on its post-translational modifications. Interestingly, this antibody also targets mammalian tubulin only present in brain, staining in and around cell bodies of the human peripheral and central nervous system. Interpretation: Our findings demonstrate for the first time the existence of a human antibody against T. cruzi tubulin capable of cross-reacting with a human neural protein. This work re-emphasizes the role of molecular mimicry between host and parasitic antigens in the development of pathological manifestations of T. cruzi infection

Tumor expression of cyclin-dependent kinase 5 (Cdk5) is a prognostic biomarker and predicts outcome of oxaliplatin-treated metastatic colorectal cancer patients

In recent years, an increasing number of studies have shown that elevated expression of cyclin dependent kinase (Cdk5) contributes to the oncogenic initiation and progression of many types of cancers. In this study, we investigated the expression pattern of Cdk5 in colorectal cancer (CRC) cell lines and in a large number of tumor samples in order to evaluate its relevance in this pathogenesis and possible use as a prognostic marker. We found that Cdk5 is highly expressed and activated in CRC cell lines and that silencing of the kinase decreases their migration ability. In tumor tissues, Cdk5 is overexpressed compared to normal tissues due to a copy number gain. In patients with localized disease, we found that high Cdk5 levels correlate with poor prognosis, while in the metastatic setting, this was only the case for patients receiving an oxaliplatin-based treatment. When exploring the Cdk5 levels in the consensus molecular subtypes (CMS), we found the lowest levels in subtype 1, where high Cdk5 again was associated with a poorer prognosis. In conclusion, we confirm that Cdk5 is involved in CRC and disease progression and that it could serve as a prognostic and predictive biomarker in this disease

A planetary-scale disturbance in a long living three vortex coupled system in Saturn's atmosphere

The zonal wind profile of Saturn has a unique structure at 60°N with a double-peaked jet that reaches maximum zonal velocities close to 100 ms−1. In this region, a singular group of vortices consisting of a cyclone surrounded by two anticyclones was active since 2012 until the time of this report. Our observation demonstrates that vortices in Saturn can be long-lived. The three-vortex system drifts at u = 69.0 ± 1.6 ms−1, similar to the speed of the local wind. Local motions reveal that the relative vorticity of the vortices comprising the system is ∼2–3 times the ambient zonal vorticity. In May 2015, a disturbance developed at the location of the triple vortex system, and expanded eastwards covering in two months a third of the latitudinal circle, but leaving the vortices essentially unchanged. At the time of the onset of the disturbance, a fourth vortex was present at 55°N, south of the three vortices and the evolution of the disturbance proved to be linked to the motion of this vortex. Measurements of local motions of the disturbed region show that cloud features moved essentially at the local wind speeds, suggesting that the disturbance consisted of passively advecting clouds generated by the interaction of the triple vortex system with the fourth vortex to the south. Nonlinear simulations are able to reproduce the stability and longevity of the triple vortex system under low vertical wind shear and high static stability in the upper troposphere of Saturn.This work was supported by the Spanish MICIIN projects AYA2015-65041-P (MINECO/FEDER, UE), Grupos Gobierno Vasco IT-765-13, and UFI11/55 from UPV/EHU. EGM is supported by the Serra Hunter Programme, Generalitat de Catalunya. A. Simon, K. Sayanagi and M.H. Wong were supported by a NASA Cassini Data Analysisgrant (NNX15AD33G and NNX15AD34G). We acknowledge the three orbits assigned by the Director Discretionary time from HST for this research (DD Program 14064, IP A. Sánchez-Lavega). We are very grateful to amateur astronomers contributing with their images to open databases such as PVOL (http://pvol2.ehu.eus/) and ALPO-Japan (http://alpo-j.asahikawa-med.ac.jp/)

An enduring rapidly moving storm as a guide to Saturn’s Equatorial jet’s complex structure

Saturn has an intense and broad eastward equatorial jet with a complex three-dimensional structure mixed with time variability. The equatorial region experiences strong seasonal insolation variations enhanced by ring shadowing, and three of the six known giant planetary-scale storms have developed in it. These factors make Saturn's equator a natural laboratory to test models of jets in giant planets. Here we report on a bright equatorial atmospheric feature imaged in 2015 that moved steadily at a high speed of 450 ms(-1) not measured since 1980-1981 with other equatorial clouds moving within an ample range of velocities. Radiative transfer models show that these motions occur at three altitude levels within the upper haze and clouds. We find that the peak of the jet ( latitudes 10 degrees N to 10 degrees S) suffers intense vertical shears reaching + 2.5 ms(-1) km(1), two orders of magnitude higher than meridional shears, and temporal variability above 1 bar altitude level. Palabras claveThis work is based on observations and analysis from Hubble Space Telescope (GO/DD program 14064), Cassini ISS images (NASA pds), and Calar Alto Observatory (CAHA-MPIA). A.S.-L. and UPV/EHU team are supported by the Spanish projects AYA2012-36666 and AYA2015-65041-P with FEDER support, Grupos Gobierno Vasco IT-765-13, Universidad del Pais Vasco UPV/EHU program UFI11/55, and Diputacion Foral Bizkaia (BFA). We acknowledge the contribution of Saturn images by T. Olivetti, M. Kardasis, A. Germano, A. Wesley, P. Miles, M. Delcroix, C. Go, T. Horiuchi and P. Maxon. We also acknowledge the wind model data provided by J. Friedson

The Role of Oestrogen Receptor Beta (ERβ) in the Aetiology and Treatment of Type 2 Diabetes Mellitus

Introduction: Challenges facing the treatment of type 2 diabetes necessitate the search for agents which act via alternative pathways to provide better therapeutic outcomes. Recently, an increasing body of evidence implicates the activation of oestrogen receptors (ERα and ERβ) in the development and treatment of underlying conditions in type 2 diabetes. This article summarizes available evidence for the involvement of oestrogen receptors in insulin secretion, insulin resistance as well as glucose uptake and highlights the potential of ERβ as a therapeutic target. Background: Recent studies indicate an association between the activation of each of the isoforms of ER and recent findings indicate that ERβ shows promise as a potential target for antidiabetic drugs. In vitro and in vivo studies in receptor knockout mice indicate beneficial actions of selective agonists of ERβ receptor and underscore its therapeutic potential. Conclusion: Studies are needed to further elucidate the exact mechanism underlying the role of ERβ activation as a therapeutic approach in the management of type 2 diabetes