Mitochondrial permeabilization engages NF-κB-dependent anti-tumour activity under caspase deficiency

Apoptosis represents a key anti-cancer therapeutic effector mechanism. During apoptosis, mitochondrial outer membrane permeabilization (MOMP) typically kills cells even in the absence of caspase activity. Caspase activity can also have a variety of unwanted consequences that include DNA damage. We therefore investigated whether MOMP-induced caspase-independent cell death (CICD) might be a better way to kill cancer cells. We find that cells undergoing CICD display potent pro-inflammatory effects relative to apoptosis. Underlying this, MOMP was found to stimulate NF-κB activity through the downregulation of inhibitor of apoptosis proteins. Strikingly, engagement of CICD displays potent anti-tumorigenic effects, often promoting complete tumour regression in a manner dependent on intact immunity. Our data demonstrate that by activating NF-κB, MOMP can exert additional signalling functions besides triggering cell death. Moreover, they support a rationale for engaging caspase-independent cell death in cell-killing anti-cancer therapies

Evaluating a multicomponent program to improve hypertension control in Guatemala: Study protocol for an effectiveness-implementation cluster randomized trial

Background: Hypertension is a major risk factor for cardiovascular disease (CVD). Despite advances in hypertension prevention and treatment, the proportion of patients who are aware, treated and controlled is low, particularly in low-income and middle-income countries (LMICs). We will evaluate an adapted version of a multilevel and multicomponent hypertension control program in Guatemala, previously proven effective and feasible in Argentina. The program components are: protocol-based hypertension treatment using a standardized algorithm; team-based collaborative care; health provider education; health coaching sessions; home blood pressure monitoring; blood pressure audit; and feedback.Methods: Using a hybrid type 2 effectiveness-implementation design, we will evaluate clinical and implementation outcomes of the multicomponent program in Guatemala over an 18-month period. Through a cluster randomized trial, we will randomly assign 18 health districts to the intervention arm and 18 to enhanced usual care across five departments, enrolling 44 participants per health district and 1584 participants in total. The clinical outcomes are (1) the difference in the proportion of patients with controlled hypertension (< 130/80 mmHg) between the intervention and control groups at 18 months and (2) the net change in systolic and diastolic blood pressure from baseline to 18 months. The context-enhanced Reach, Efficacy, Adoption, Implementation, Maintenance (RE-AIM)/Practical Robust Implementation and Sustainability Model (PRISM) framework will guide the evaluation of the implementation at the level of the patient, provider, and health system. Using a mixed-methods approach, we will evaluate the following implementation outcomes: acceptability, adoption, feasibility, fidelity, adaptation, reach, sustainability, and cost-effectiveness.Discussion: We will disseminate the study findings, and promote scale up and scale out of the program, if proven effective. This study will generate urgently needed data on effective, adoptable, and sustainable interventions and implementation strategies to improve hypertension control in Guatemala and other LMICs.Fil: Paniagua Avila, Alejandra. Columbia University; Estados UnidosFil: Fort, Meredith P.. Institute Of Nutrition Of Central America And Panamá; GuatemalaFil: Glasgow, Russell E.. University of Colorado; Estados UnidosFil: Gulayin, Pablo Elías. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Hernández Galdamez, Diego. institute of Nutrition of Central America and Panamá; GuatemalaFil: Mansilla, Kristyne. institute of Nutrition of Central America and Panamá; GuatemalaFil: Palacios, Eduardo. Ministerio de Salud y Asistencia Social; GuatemalaFil: Peralta, Ana Lucia. Institute of Nutrition of Central America and Panamá ; GuatemalaFil: Roche, Dina. Institute of Nutrition of Central America and Panamá ; GuatemalaFil: Rubinstein, Adolfo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: He, Jiang. University Translational Science Institute; Estados UnidosFil: Ramirez Zea, Manuel. Institute of Nutrition of Central America and Panamá ; GuatemalaFil: Irazola, Vilma. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Realistic simulations of gravitational lensing by galaxy clusters: extracting arc parameters from mock DUNE images

We present a newly developed code that allows simulations of optical observations of galaxy fields with a variety of instruments. The code incorporates gravitational lensing effects and is targetted at simulating lensing by galaxy clusters. Our goal is to create the tools required for comparing theoretical expectations with observations to obtain a better understanding of how observational noise affects lensing applications such as mass estimates, studies on the internal properties of galaxy clusters and arc statistics. Starting from a set of input parameters, characterizing both the instruments and the observational conditions, the simulator provides a virtual observation of a patch of the sky. It includes several sources of noise such as photon-noise, sky background, seeing, and instrumental noise. Ray-tracing through simulated mass distributions accounts for gravitational lensing. Source morphologies are realistically simulated based on shapelet decompositions of galaxy images retrieved from the GOODS-ACS archive. According to their morphological class, spectral-energy-distributions are assigned to the source galaxies in order to reproduce observations of each galaxy in arbitrary photometric bands. We illustrate our techniques showing virtual observations of a galaxy-cluster core as it would be observed with the space telescope DUNE, which was recently proposed to ESA within its "Cosmic vision" programme. (Abridged)Comment: 17 pages, 15 figures submitted to A&

EDisCS -- the ESO Distant Cluster Survey -- Sample Definition and Optical Photometry

We present the ESO Distant Cluster Survey (EDisCS) a survey of 20 fields containing distant galaxy clusters with redshifts ranging from 0.4 to almost 1.0. Candidate clusters were chosen from among the brightest objects identified in the Las Campanas Distant Cluster Survey, half with estimated redshift z_est~0.5 and half with z_est~0.8. They were confirmed by identifying red sequences in moderately deep two colour data from VLT/FORS2. For confirmed candidates we have assembled deep three-band optical photometry using VLT/FORS2, deep near-infrared photometry in one or two bands using NTT/SOFI, deep optical spectroscopy using VLT/FORS2, wide field imaging in two or three bands using the ESO Wide Field Imager, and HST/ACS mosaic images for 10 of the most distant clusters. This first paper presents our sample and the VLT photometry we have obtained. We present images, colour-magnitude diagrams and richness estimates for our clusters, as well as giving redshifts and positions for the brightest cluster members. Subsequent papers will present our infrared photometry, spectroscopy, HST and wide-field imaging, as well as a wealth of further analysis and science results. Our reduced data become publicly available as these papers are accepted.Comment: 21 pages, 6 figures, A&A in press. A version with full resolution figures is available at http://www.mpa-garching.mpg.de/ediscs/papers.htm

Evaluation of the applicability of nano-biocide treatments on limestones used in cultural heritage.

One of the main problems in the conservation of historical buildings and archaeological sites is theone caused by biodeterioration. Biopatina, biocrust or biofouling generate aesthetical changes andinduce degradation processes within the stone matrix. In this work, three treatments based on sil-ver nanoparticles and silver/titanium dioxide nanocomposites have been studied as potential biocidesfor limestones: citrate-stabilized silver nanoparticles, silver/TiO2nanocomposites and citrate-stabilizedsilver/TiO2nanocomposites. These treatments were synthesized following a bottom-up method, using ornot a stabilizing agent (citrate), and have been characterized by UV-Visible spectrophotometry, DynamicLight Scattering and Raman spectroscopy. These treatments were applied on limestones from three differ-ent Spanish quarries located in Utrera (Seville), El Puerto de Santa María (Cadiz) and Novelda (Alicante).The aesthetical modification of limestone surfaces was studied by colorimetric techniques and the effec-tiveness of protection against biofouling formation was tested using an accelerated biofouling growthassay. The best results were obtained for the treatments based on citrate-stabilized silver nanoparti-cles. The effectiveness of the treatments depends on their penetration depth in the stone matrix andin this study, we have used Laser Induced Breakdown Spectroscopy to determine the depth profilesof nanocomposite presence in the stone matrix. Our results demonstrate that nanocomposites basedon citrate-stabilized silver nanoparticles can be useful for the treatment of historical buildings andarchaeological sites made of limestone, without producing high colour increments. Additionally, we have demonstrated the suitability of Laser Induced Breakdown Spectroscopy for the detection of silver/TiO2nanocomposites and for the generation of depth profiles.Departamento de Sistemas Físicos, Químicos y Naturales, Universidad Pablo de Olavide,Departamento de Ingeniería Industrial II, laser Applications laboratory, Universidade da Coruña,Preprin

Anasarca, Julia, Spirit Assembly, The Divisionaries, and 400 Years concert flier, Happy Hardcore House, Washington, D.C., June 19, 1996

Flier promoting a concert by the punk bands Anasarca, Julia, Spirit Assembly, The Divisionaries, and 400 Years. The concert was held at the Happy Hardcore House (located at 619 22nd St. NW) in Washington, D.C., on June 19, 1996

Dermatological clues to the diagnosis of atypical complete DiGeorge syndrome

Atypical complete DiGeorge syndrome (DGS) is an extremely rare congenital disease characterized by an eczematous dermatitis, lymphadenopathy, and an oligoclonal T-cell proliferation. Because its initial presentation may be confused with other types of eczematous dermatitis, diagnosis and treatment are usually delayed. We describe herein a case of an infant with atypical complete DGS to draw attention to the clinical and histopathological findings that lead us to the diagnosis