On the complete digraphs which are simply disconnected

Homotopic methods are employed for the characterization of the complete digraphs which are the composition of non-trivial highly regular tournaments

Le condizioni semiotiche di accesso al lutto. Il Parque de la Memoria y los derechos humanos di Buenos Aires

The access to the dignity of mourning, that is the possibility for a given community to remember the dead and to transmit their memory, requires several semiotic acts of mediation. In this paper we concentrate on the Argentina case during its postdictatorship phase during which a number of places of memories have been created and peculiar rituals of commemoration in the urban space have been envisaged in order to remember the desaparecidos. The second part of this article is dedicated to the Parque de la memoria y los derechos humanos, located on the Rio de la Plata, very close to the airport from which the \u201cflights of death\u201d used to take off. How does the park represent a space that may help the working through of a traumatic past for those who have disappeared? And how does the design of this space constitute a peculiar practice of urban commemoration

Baseline T cell dysfunction by single cell network profiling in metastatic breast cancer patients.

BackgroundWe previously reported the results of a multicentric prospective randomized trial of chemo-refractory metastatic breast cancer patients testing the efficacy of two doses of TGFβ blockade during radiotherapy. Despite a lack of objective responses to the combination, patients who received a higher dose of TGFβ blocking antibody fresolimumab had a better overall survival when compared to those assigned to lower dose (hazard ratio of 2.73, p = 0.039). They also demonstrated an improved peripheral blood mononuclear cell (PBMC) counts and increase in the CD8 central memory pool. We performed additional analysis on residual PBMC using single cell network profiling (SCNP).MethodsThe original trial randomized metastatic breast cancer patients to either 1 or 10 mg/kg of fresolimumab, every 3 weeks for 5 cycles, combined with radiotherapy to a metastatic site at week 1 and 7 (22.5 Gy given in 3 doses of 7.5 Gy). Trial immune monitoring results were previously reported. In 15 patients with available residual blood samples, additional functional studies were performed, and compared with data obtained in parallel from seven healthy female donors (HD): SCNP was applied to analyze T cell receptor (TCR) modulated signaling via CD3 and CD28 crosslinking and measurement of evoked phosphorylation of AKT and ERK in CD4 and CD8 T cell subsets defined by PD-1 expression.ResultsAt baseline, a significantly higher level of expression (p < 0.05) of PD-L1 was identified in patient monocytes compared to HD. TCR modulation revealed dysfunction of circulating T-cells in patient baseline samples as compared to HD, and this was more pronounced in PD-1+ cells. Treatment with radiotherapy and fresolimumab did not resolve this dyfunctional signaling. However, in vitro PD-1 blockade enhanced TCR signaling in patient PD-1+ T cells and not in PD-1- T cells or in PD-1+ T cells from HD.ConclusionsFunctional T cell analysis suggests that baseline T cell functionality is hampered in metastatic breast cancer patients, at least in part mediated by the PD-1 signaling pathway. These preliminary data support the rationale for investigating the possible beneficial effects of adding PD-1 blockade to improve responses to TGFβ blockade and radiotherapy.Trial registrationNCT01401062

Evaluation of mesoscale convective systems in South America using multiple satellite products and an object‐based approach

In this study, an object-based verification method was used to reveal the existence of systematic errors in three satellite precipitation products: Tropical Rainfall Measurement Mission (TRMM), Climate Prediction Center Morphing Technique (CMORPH), and Precipitation Estimation from Remotely Sensed Information Using Artificial Neural Networks (PERSIANN). Mesoscale convective systems (MCSs) for the austral summer 2002–2003 in the La Plata river basin, southeastern South America, were analyzed with the Contiguous Rain Area (CRA) method. Errors in storms intensity, volume, and spatial location were evaluated. A macroscale hydrological model was used to assess the impact of spatially shifted precipitation on streamflows simulations. PERSIANN underestimated the observed average rainfall rate and maximum rainfall consistent with the detection of storm areas systematically larger than observed. CMORPH overestimated the average rainfall rate while the maximum rainfall was slightly underestimated. TRMM average rainfall rate and rainfall volume correlated extremely well with ground observations whereas the maximum rainfall was systematically overestimated suggesting deficiencies in the bias correction procedure to filter noisy measurements. The preferential direction of error displacement in satellite-estimated MCSs was in the east-west direction for CMORPH and TRMM. Discrepancies in the fine structure of the storms dominated the error decomposition of all satellite products. Errors in the spatial location of the systems influenced the magnitude of simulated peaks but did not have a significant impact on the timing indicating that the system's response to precipitation was mitigating the effect of the errors.Fil: Demaria, E. M. C.. University Of Arizona; Estados UnidosFil: Rodriguez, D. A.. Centro de Previsao de Tempo e Estudos Climaticos. Instituto Nacional de Pesquisas Espaciais; BrasilFil: Ebert, E. E.. Centre for Australian Weather and Climate Research; AustraliaFil: Salio, Paola Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmosfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmosfera; ArgentinaFil: Su, F.. University of Washington; Estados UnidosFil: Valdes, J. B.. University Of Arizona; Estados Unido

Interleukin 23-Helper T Cell 17 Axis as a Treatment Target for Pityriasis Rubra Pilaris.

Treatment of pityriasis rubra pilaris (PRP) is solely based on its resemblance to psoriasis rather than any knowledge of its pathomechanism. Insight into pathogenic mediators of inflammation is essential for targeted and valid treatment options that could replace previous serendipitous therapeutic approaches in refractory PRP. To determine whether blockade of the interleukin 23-helper T cell 17 (IL-23-TH17) pathway with ustekinumab represents an efficacious and, based on its proinflammatory cytokine profile, targeted treatment option in PRP. In this case report, a patient with PRP received outpatient treatment at a university hospital department of dermatology with ustekinumab according to the dosing regimen approved for psoriasis. Lesional skin biopsy samples were taken from this patient and 2 others with refractory PRP. Messenger RNA (mRNA) expression of proinflammatory innate and T-cell-derived cytokines were measured and compared with skin samples from patients with psoriasis and healthy donors. From 1 patient, lesional skin samples were taken before ustekinumab treatment and 4 and 28 weeks after treatment initiation. Follow-up was completed after 6 months. Subcutaneous ustekinumab, 45 mg, at weeks 0 and 4 and quarterly thereafter. The primary outcome was to determine the changes in expression of proinflammatory innate and T-cell-derived cytokines during ustekinumab therapy. The secondary objective was to evaluate the clinical and histopathologic phenotype in relation to the mRNA expression profile of proinflammatory cytokines. In lesional PRP skin samples from a single patient, upregulated expression levels were found for most proinflammatory innate cytokines, including tumor necrosis factor (TNF), IL-6, IL-12, IL-23, and IL-1β. Among adaptive T-cell cytokines, an increase of TH1 cytokines and, in particular, TH17 cytokines IL-17A, IL-17F, and IL-22 was seen in PRP. The patient with PRP who received ustekinumab showed regression of skin lesions after 2 weeks and almost complete resolution after 1 month. Clinical and histopathologic improvement paralleled the expression levels of TH17 cytokines but not of interferon-γ and TNF, which lagged behind the amelioration. In this case report, a role of the IL-23-TH17-axis in PRP was identified, suggesting a shared pathogenic inflammatory pathway with psoriasis, despite evident clinical and histopathologic differences. In addition, this report provides a rationale for targeting the IL-23-TH17-pathway as a treatment option for refractory PRP

Overview of the NASA TROPICS CubeSat Constellation Mission

Recent technology advances in miniature microwave radiometers that can be hosted on very small satellites has made possible a new class of affordable constellation missions that provide very high revisit rates of tropical cyclones and other severe weather. The Time-Resolved Observations of Precipitation structure and storm Intensity with a Constellation of Smallsats (TROPICS) mission was selected by NASA as part of the Earth VentureInstrument (EVI-3) program and is now in development with planned launch readiness in late 2019. The overarching goal for TROPICS is to provide nearly all-weather observations of 3-D temperature and humidity, as well as cloud ice and precipitation horizontal structure, at high temporal resolution to conduct high-value science investigations of tropical cyclones (TCs). TROPICS will provide rapid-refresh microwave measurements (median refresh rate better than 60 minutes for the baseline mission) over the tropics that can be used to observe the thermodynamics of the troposphere and precipitation structure for storm systems at the mesoscale and synoptic scale over the entire storm lifecycle. TROPICS will comprise a constellation of at least six CubeSats in three low-Earth orbital planes. Each CubeSat will host a high performance radiometer to provide temperature profiles using seven channels near the 118.75 GHz oxygen absorption line, water vapor profiles using three channels near the 183 GHz water vapor absorption line, imagery in a single channel near 90 GHz for precipitation measurements (when combined with higher resolution water vapor channels), and a single channel at 205 GHz that is more sensitive to precipitation-sized ice particles and low-level moisture. This observing system offers an unprecedented combination of horizontal and temporal resolution in the microwave spectrum to measure environmental and inner-core conditions for TCs on a nearly global scale and is a major leap forward in the temporal resolution of several key parameters needed for assimilation into advanced data assimilation systems capable of utilizing rapid-update radiance or retrieval data. Here, we provide an overview of the mission and an update on current status, with a focus on unique characteristics of the Cubesat system, recent performance simulations on a range of observables to be provided by the constellation, and a summary of science applications

Overview of the NASA TROPICS CubeSat Constellation Mission

Recent technology advances in miniature microwave radiometers that can be hosted on very small satellites has made possible a new class of affordable constellation missions that provide very high revisit rates of tropical cyclones and other severe weather. The Time-Resolved Observations of Precipitation structure and storm Intensity with a Constellation of Smallsats (TROPICS) mission was selected by NASA as part of the Earth Venture-Instrument (EVI-3)program and is now in development with planned launch readiness in late 2019. The overarching goal for TROPICS is to provide nearly all-weather observations of 3-D temperature and humidity, as well as cloud ice and precipitation horizontal structure, at high temporal resolution to conduct high-value science investigations of tropical cyclones (TCs). TROPICS will provide rapid-refresh microwave measurements (median refresh rate better than 60 minutes for the baseline mission) over the tropics that can be used to observe the thermodynamics of the troposphere and precipitation structure for storm systems at the mesoscale and synoptic scale over the entire storm life cycle. TROPICS will comprise a constellation of at least six CubeSats in three low-Earth orbital planes. Each CubeSat will host a high performance radiometer to provide temperature profiles using seven channels near the 118.75 GHz (gigahertz) oxygen absorption line, water vapor profiles using three channels near the 183 GHz water vapor absorption line, imagery in a single channel near 90 GHz for precipitation measurements (when combined with higher resolution water vapor channels), and a single channel at 205 GHz that is more sensitive to precipitation-sized ice particles and low-level moisture. This observing system offers an unprecedented combination of horizontal and temporal resolution in the microwave spectrum to measure environmental and inner-core conditions for TCs on a nearly global scale and is a major leap forward in the temporal resolution of several key parameters needed for assimilation into advanced data assimilation systems capable of utilizing rapid-update radiance or retrieval data. Here, we provide an overview of the mission and an update on current status,with a focus on unique characteristics of the Cubesat system, recent performance simulations on a range of observables to be provided by the constellation, and a summary of science applications