Utilizing blockchain technology for supply chain transparency: A resource orchestration perspective

Driven by pressures from multiple stakeholders, supply chain transparency (SCT) has emerged as a phenomenon of increased interest. To address concerns about practices and processes at point of origin locations for raw materials in global supply chains, blockchain technology (BCT) has the potential to enhance SCT. Supply chain research has started to advance the field's understanding of SCT, but many questions remain, including how SCT should be conceptualized, how firms can effectively facilitate it, and the benefits of providing it, especially when BCT is utilized. The gaps suggest the need for fundamental theoretical development about the resources and capabilities underlying the development, application, and derived value of SCT. This research designed a case study around a BCT implementation project between a small artisan coffee producer and a startup BCT service provider. Using the resource orchestration perspective, the findings result in theoretical insights about how the mechanisms in structuring, bundling, and leveraging processes operate to offer SCT to stakeholders, and the value creation derived as a result

The First Two Years of Electromagnetic Follow-Up with Advanced LIGO and Virgo

We anticipate the first direct detections of gravitational waves (GWs) with Advanced LIGO and Virgo later this decade. Though this groundbreaking technical achievement will be its own reward, a still greater prize could be observations of compact binary mergers in both gravitational and electromagnetic channels simultaneously. During Advanced LIGO and Virgo's first two years of operation, 2015 through 2016, we expect the global GW detector array to improve in sensitivity and livetime and expand from two to three detectors. We model the detection rate and the sky localization accuracy for binary neutron star (BNS) mergers across this transition. We have analyzed a large, astrophysically motivated source population using real-time detection and sky localization codes and higher-latency parameter estimation codes that have been expressly built for operation in the Advanced LIGO/Virgo era. We show that for most BNS events the rapid sky localization, available about a minute after a detection, is as accurate as the full parameter estimation. We demonstrate that Advanced Virgo will play an important role in sky localization, even though it is anticipated to come online with only one-third as much sensitivity as the Advanced LIGO detectors. We find that the median 90% confidence region shrinks from ~500 square degrees in 2015 to ~200 square degrees in 2016. A few distinct scenarios for the first LIGO/Virgo detections emerge from our simulations.Comment: 17 pages, 11 figures, 5 tables. For accompanying data, see http://www.ligo.org/scientists/first2year

Parameter estimation on gravitational waves from neutron-star binaries with spinning components

Inspiraling binary neutron stars are expected to be one of the most significant sources of gravitational-wave signals for the new generation of advanced ground-based detectors. We investigate how well we could hope to measure properties of these binaries using the Advanced LIGO detectors, which began operation in September 2015. We study an astrophysically motivated population of sources (binary components with masses $1.2~\mathrm{M}_\odot$--$1.6~\mathrm{M}_\odot$ and spins of less than $0.05$) using the full LIGO analysis pipeline. While this simulated population covers the observed range of potential binary neutron-star sources, we do not exclude the possibility of sources with parameters outside these ranges; given the existing uncertainty in distributions of mass and spin, it is critical that analyses account for the full range of possible mass and spin configurations. We find that conservative prior assumptions on neutron-star mass and spin lead to average fractional uncertainties in component masses of $\sim 16\%$, with little constraint on spins (the median $90\%$ upper limit on the spin of the more massive component is $\sim 0.7$). Stronger prior constraints on neutron-star spins can further constrain mass estimates, but only marginally. However, we find that the sky position and luminosity distance for these sources are not influenced by the inclusion of spin; therefore, if LIGO detects a low-spin population of BNS sources, less computationally expensive results calculated neglecting spin will be sufficient for guiding electromagnetic follow-up.Comment: 10 pages, 9 figure

Supplement: Going the Distance: Mapping Host Galaxies of LIGO and Virgo Sources in Three Dimensions Using Local Cosmography and Targeted Follow-up

This is a supplement to the Letter of Singer et al. (https://arxiv.org/abs/1603.07333), in which we demonstrated a rapid algorithm for obtaining joint 3D estimates of sky location and luminosity distance from observations of binary neutron star mergers with Advanced LIGO and Virgo. We argued that combining the reconstructed volumes with positions and redshifts of possible host galaxies can provide large-aperture but small field of view instruments with a manageable list of targets to search for optical or infrared emission. In this Supplement, we document the new HEALPix-based file format for 3D localizations of gravitational-wave transients. We include Python sample code to show the reader how to perform simple manipulations of the 3D sky maps and extract ranked lists of likely host galaxies. Finally, we include mathematical details of the rapid volume reconstruction algorithm.Comment: For associated data release, see http://asd.gsfc.nasa.gov/Leo.Singer/going-the-distanc

Oncolytic adenoviruses coated with MHC-I tumor epitopes increase the anti-tumor immunity and efficacy against melanoma

The stimulation of the immune system using oncolytic adenoviruses (OAds) has attracted significant interest and several studies suggested that OAd´s immunogenicity might be important for their efficacy. Therefore, we developed a versatile and rapid system to adsorb tumor-specific major histocompatibility complex class I (MHC-I) peptides onto the viral surface to drive the immune response towards the tumor-epitopes. By studying the model epitope SIINFEKL we demonstrated that the peptide-coated OAd (PeptiCRAd) retains its infectivity and the cross-presentation of the modified-exogenous epitope on MHC-I is not hindered. We then showed that the SIINFEKL-targeting PeptiCRAd achieves a superior anti-tumor efficacy and increases the percentage of anti-tumor CD8+ T-cells and mature epitope-specific dendritic cells in vivo. PeptiCRAds loaded with clinically relevant tumor epitopes derived from tyrosinase-related protein 2 (TRP-2) and human gp100 could reduce the growth of primary-treated tumors and secondary-untreated melanomas, promoting the expansion of antigen-specific T-cell populations. Finally, we tested PeptiCRAd in humanized mice bearing human melanomas. In this model, a PeptiCRAd targeting the human melanoma-associated antigen A1 (MAGE-A1) and expressing granulocyte and macrophage colony-stimulating factor (GM-CSF) was able to eradicate established tumors and increased the human MAGE-A1-specific CD8+ T-cell population. Herein we show that the immunogenicity of OAds plays a key role in their efficacy and it can be exploited to direct the immune response system towards exogenous tumor epitopes. This versatile and rapid system overcomes the immunodominance of the virus and elicits a tumor-specific immune response, making PeptiCRAd a promising approach for clinical testing.Peer reviewe

Vitamin D analogues exhibit antineoplastic activity in breast cancer patient-derived xenograft cells

Despite advances in breast cancer (BC) treatment, its mortality remains high due to intrinsic or acquired resistance to therapy. Several ongoing efforts are being made to develop novel drugs to treat this pathology with the aim to overcome resistance, prolong patient survival and improve their quality of life. We have previously shown that the non-hypercalcemic vitamin D analogues EM1 and UVB1 display antitumor effects in preclinical studies employing conventional cell lines and animal models developed from these cells. In this work, we explored the antitumor effects of EM1 and UVB1 employing BC cells derived from patient-derived xenografts (PDXs), which are a powerful preclinical tool for testing new drugs. We demonstrated that the analogues reduced the viability of HER2-positive and Triple Negative BC-PDXs. Moreover, using an in vitro model of acquired resistance to Trastuzumab-emtansine, UVB1 displayed anti-proliferative actions under 2D and 3D culture conditions. It inhibited both formation and growth of established organoids. In addition, a direct correlation between UVB1 antitumor effects and VDR expression in PDXs was found. In conclusion, all the results reinforce the potential use of these vitamin D analogues as antitumor agents to treat HER2-positive and Triple Negative BC.Fil: Ferronato, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Nadal, Serrano Mercedes. Universidad Autonoma de Barcelona. Hospital Vall D' Hebron. Instituto de Investigación Vall D'hebron; EspañaFil: Arenas Lahuerta, Enrique Javier. Universidad Autonoma de Barcelona. Hospital Vall D' Hebron. Instituto de Investigación Vall D'hebron; EspañaFil: Morales, Cristina Bernadó. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; EspañaFil: Paolillo, Giuliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Martinez Sabadell, Aliguer Alex. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; EspañaFil: Mascaró, Marilina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Vitale, Cristian Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Fall, Yagamare. Universidad de Vigo; EspañaFil: Arribas, Joaquín. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; España. Universitat Autònoma de Barcelona; España. Centro de Investigación Biomédica en Red de Cáncer; España. Institució Catalana de Recerca i Estudis Avancats; EspañaFil: Facchinetti, María Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentin

Lead silicate glass structure : new insights from diffraction and modeling of probable lone pair locations

Structures of binary PbO‐SiO2 glasses have been studied in detail over the compositional range 35 to 80 mol% PbO using high‐resolution neutron diffraction, high‐energy X‐ray diffraction, static 207Pb NMR, and structural modeling. The changes in the local environment of Pb(II) are subtle; it has a low coordination to oxygen (∼3 to 4) plus a stereochemically active electron lone pair and, thus, behaves as a glass network forming (or intermediate) cation over the entire composition range. This conclusion contradicts previous reports that Pb(II) is a network modifier at low concentrations, and is supported by an analysis of lead and alkaline earth silicate glass molar volumes. The Pb‐O peak bond length shortens by 0.04 Å with increasing PbO content, indicating stronger, more covalent bonding, and consistent with an increase in the number of short (≤ 2.70 Å) Pb‐O bonds, from 3.3 to 3.6. This is accompanied by increased axial symmetry of the Pb(II) sites, and is interpreted as a gradual transition toward square pyramidal [PbO4] sites such as those found in crystalline PbO polymorphs. An attendant decrease in the periodicity associated with the first sharp diffraction peak (FSDP) toward that of β‐PbO, accompanied by increases in the correlation lengths associated with the plumbite network (FSDP) and silicate anions (neutron prepeak), provides evidence of increased intermediate‐range order and has implications for the glass forming limit imposed by crystallization. Pb(II) electron lone pairs occupy the natural voids within the silicate network at low PbO contents, while at high PbO contents they aggregate to create voids that form part of the plumbite network, analogous to the open channels in Pb11Si3O17 and the layered structures of α‐ and β‐PbO. Si‐O and Pb‐O bond lengths have been correlated with 29Si and 207Pb NMR chemical shifts, respectively. This is the first time that such correlations have been demonstrated for glasses and attests to the accuracy with which pulsed neutron total scattering can measure average bond lengths

Parameter Estimation for Binary Neutron-star Coalescences with Realistic Noise during the Advanced LIGO Era

Advanced ground-based gravitational-wave (GW) detectors begin operation imminently. Their intended goal is not only to make the first direct detection of GWs, but also to make inferences about the source systems. Binary neutron-star mergers are among the most promising sources. We investigate the performance of the parameter-estimation (PE) pipeline that will be used during the first observing run of the Advanced Laser Interferometer Gravitational-wave Observatory (aLIGO) in 2015: we concentrate on the ability to reconstruct the source location on the sky, but also consider the ability to measure masses and the distance. Accurate, rapid sky localization is necessary to alert electromagnetic (EM) observatories so that they can perform follow-up searches for counterpart transient events. We consider PE accuracy in the presence of non-stationary, non-Gaussian noise. We find that the character of the noise makes negligible difference to the PE performance at a given signal-to-noise ratio. The source luminosity distance can only be poorly constrained, since the median 90% (50%) credible interval scaled with respect to the true distance is 0.85 (0.38). However, the chirp mass is well measured. Our chirp-mass estimates are subject to systematic error because we used gravitational-waveform templates without component spin to carry out inference on signals with moderate spins, but the total error is typically less than 10^(-3) M_☉. The median 90% (50%) credible region for sky localization is ~ 600 deg^2 (~150 deg^2), with 3% (30%) of detected events localized within 100 deg^2. Early aLIGO, with only two detectors, will have a sky-localization accuracy for binary neutron stars of hundreds of square degrees; this makes EM follow-up challenging, but not impossible

Update on ocular manifestations of the main monogenic and polygenic autoinflammatory diseases

Autoinflammatory diseases include disorders with a genetic cause and also complex syndromes associated to polygenic or multifactorial factors. Eye involvement is present in many of them, with different extent and severity. The present review covers ophthalmological lesions in the most prevalent monogenic autoinflammatory diseases, including FMF (familial Mediterranean fever), TRAPS (TNF receptor-associated periodic syndrome), CAPS (cryopyrin-associated periodic syndromes), Blau syndrome, DADA2 (deficiency of adenosine deaminase 2), DITRA (deficiency of the interleukin-36 receptor antagonist), other monogenic disorders, including several ubiquitinopathies, interferonopathies, and the recently described ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome, and VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Among polygenic autoinflammatory diseases, ocular manifestations have been reviewed in Behçet’s disease, PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) syndrome, Still’s disease and autoinflammatory bone diseases, which encompass CRMO (chronic recurrent multifocal osteomyelitis) and SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome

Supplement: "Going the Distance: Mapping Host Galaxies of LIGO and Virgo Sources in Three Dimensions Using Local Cosmography and Targeted Follow-up" (2016, ApJL, 829, L15)

This is a supplement to the Letter of Singer et al., in which we demonstrated a rapid algorithm for obtaining joint 3D estimates of sky location and luminosity distance from observations of binary neutron star mergers with Advanced LIGO and Virgo. We argued that combining the reconstructed volumes with positions and redshifts of possible host galaxies can provide large-aperture but small field of view instruments with a manageable list of targets to search for optical or infrared emission. In this Supplement, we document the new HEALPix-based file format for 3D localizations of gravitational-wave transients. We include Python sample code to show the reader how to perform simple manipulations of the 3D sky maps and extract ranked lists of likely host galaxies. Finally, we include mathematical details of the rapid volume reconstruction algorithm