BACKGROUND Preclinical experiments have shown that donor blood cells, modified in vitro by an alkylating agent (modified immune cells [MICs]), induced long-term specific immunosuppression against the allogeneic donor.METHODS In this phase I trial, patients received either 1.5 × 106 MICs per kg BW on day –2 (n = 3, group A), or 1.5 × 108 MICs per kg BW on day –2 (n = 3, group B) or day –7 (n = 4, group C) before living donor kidney transplantation in addition to post-transplantation immunosuppression. The primary outcome measure was the frequency of adverse events (AEs) until day 30 (study phase) with follow-up out to day 360.RESULTS MIC infusions were extremely well tolerated. During the study phase, 10 treated patients experienced a total of 69 AEs that were unlikely to be related or not related to MIC infusion. No donor-specific human leukocyte antigen Abs or rejection episodes were noted, even though the patients received up to 1.3 × 1010 donor mononuclear cells before transplantation. Group C patients with low immunosuppression during follow-up showed no in vitro reactivity against stimulatory donor blood cells on day 360, whereas reactivity against third-party cells was still preserved. Frequencies of CD19+CD24hiCD38hi transitional B lymphocytes (Bregs) increased from a median of 6% before MIC infusion to 20% on day 180, which was 19- and 68-fold higher, respectively, than in 2 independent cohorts of transplanted controls. The majority of Bregs produced the immunosuppressive cytokine IL-10. MIC-treated patients showed the Immune Tolerance Network operational tolerance signature.CONCLUSION MIC administration was safe and could be a future tool for the targeted induction of tolerogenic Bregs.TRIAL REGISTRATION EudraCT number: 2014-002086-30; ClinicalTrials.gov identifier: NCT02560220FUNDING Federal Ministry for Economic Affairs and Technology, Berlin, Germany, and TolerogenixX GmbH, Heidelberg, Germany.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by loss of repression of the DUX4 gene; however, the DUX4 protein is rare and difficult to detect in human muscle biopsies, and pathological mechanisms are obscure. FSHD is also a chronic disease that progresses slowly over decades. We used the sporadic, low-level, muscle-specific expression of DUX4 enabled by the iDUX4pA-HSA mouse to develop a chronic long-term muscle disease model. After 6 months of extremely low sporadic DUX4 expression, dystrophic muscle presented hallmarks of FSHD histopathology, including muscle degeneration, capillary loss, fibrosis, and atrophy. We investigated the transcriptional profile of whole muscle as well as endothelial cells and fibroadiopogenic progenitors (FAPs). Strikingly, differential gene expression profiles of both whole muscle and, to a lesser extent, FAPs, showed significant overlap with transcriptional profiles of MRI-guided human FSHD muscle biopsies. These results demonstrate a pathophysiological similarity between disease in muscles of iDUX4pA-HSA mice and humans with FSHD, solidifying the value of chronic rare DUX4 expression in mice for modeling pathological mechanisms in FSHD and highlighting the importance FAPs in this disease.

Lamin A is a component of the inner nuclear membrane that, together with epigenetic factors, organizes the genome in higher order structures required for transcriptional control. Mutations in the lamin A/C gene cause several diseases belonging to the class of laminopathies, including muscular dystrophies. Nevertheless, molecular mechanisms involved in the pathogenesis of lamin A–dependent dystrophies are still largely unknown. The polycomb group (PcG) of proteins are epigenetic repressors and lamin A interactors, primarily involved in the maintenance of cell identity. Using a murine model of Emery-Dreifuss muscular dystrophy (EDMD), we show here that lamin A loss deregulated PcG positioning in muscle satellite stem cells, leading to derepression of non–muscle-specific genes and p16INK4a, a senescence driver encoded in the Cdkn2a locus. This aberrant transcriptional program caused impairment in self-renewal, loss of cell identity, and premature exhaustion of the quiescent satellite cell pool. Genetic ablation of the Cdkn2a locus restored muscle stem cell properties in lamin A/C–null dystrophic mice. Our findings establish a direct link between lamin A and PcG epigenetic silencing and indicate that lamin A–dependent muscular dystrophy can be ascribed to intrinsic epigenetic dysfunctions of muscle stem cells.

Immunosuppression continues to be a necessary component of transplantation, despite its association with a multitude of adverse effects. Numerous efforts have been made to circumvent the need for immunosuppression by using various techniques to achieve donor hyporesponsiveness. In this issue of the JCI, Morath et al. take this endeavor forward. Prior to transplantation, the researchers infused recipients with donor-modified immune cells and achieved immunologic hyporesponsiveness. This successful phase I trial also provides a possible avenue for achieving transplantation without the requisite immunosuppression.

BACKGROUND Glucose-6-phosphate dehydrogenase (G6PD) deficiency decreases the ability of red blood cells (RBCs) to withstand oxidative stress. Refrigerated storage of RBCs induces oxidative stress. We hypothesized that G6PD-deficient donor RBCs would have inferior storage quality for transfusion as compared with G6PD-normal RBCs.METHODS Male volunteers were screened for G6PD deficiency; 27 control and 10 G6PD-deficient volunteers each donated 1 RBC unit. After 42 days of refrigerated storage, autologous 51-chromium 24-hour posttransfusion RBC recovery (PTR) studies were performed. Metabolomics analyses of these RBC units were also performed.RESULTS The mean 24-hour PTR for G6PD-deficient subjects was 78.5% ± 8.4% (mean ± SD), which was significantly lower than that for G6PD-normal RBCs (85.3% ± 3.2%; P = 0.0009). None of the G6PD-normal volunteers (0/27) and 3 G6PD-deficient volunteers (3/10) had PTR results below 75%, a key FDA acceptability criterion for stored donor RBCs. As expected, fresh G6PD-deficient RBCs demonstrated defects in the oxidative phase of the pentose phosphate pathway. During refrigerated storage, G6PD-deficient RBCs demonstrated increased glycolysis, impaired glutathione homeostasis, and increased purine oxidation, as compared with G6PD-normal RBCs. In addition, there were significant correlations between PTR and specific metabolites in these pathways.CONCLUSION Based on current FDA criteria, RBCs from G6PD-deficient donors would not meet the requirements for storage quality. Metabolomics assessment identified markers of PTR and G6PD deficiency (e.g., pyruvate/lactate ratios), along with potential compensatory pathways that could be leveraged to ameliorate the metabolic needs of G6PD-deficient RBCs.TRIAL REGISTRATION ClinicalTrials.gov NCT04081272.FUNDING The Harold Amos Medical Faculty Development Program, Robert Wood Johnson Foundation grant 71590, the National Blood Foundation, NIH grant UL1 TR000040, the Webb-Waring Early Career Award 2017 by the Boettcher Foundation, and National Heart, Lung, and Blood Institute grants R01HL14644 and R01HL148151.

Video from Thabo Meerkat, transcribed

Welcome to another edition of Digging Up Positivity! This episode is dedicated to the many volunteers that make all those amazing conventions and charities possible. But besides them, we are covering some animation news and other (maybe otter?) tidbits!

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The response of Senator Richard Blumenthal to my letter in opposition to the Trans-Pacific Partnership (TPP). Ask yourselves how American labor can compete against Vietnamese workers earning on average $0.56 per hour. Continue reading →

The Senate considered H.R. 1314, the legislative vehicle for trade promotion authority reauthorization.?It would give the president broad fast-track authority when negotiating trade agreements and require Congress to consider treaties without an amendment process. Senator Bernie Sanders speaks out against this bill before the Senate on May 12, 2015. Continue reading →

Bernie Sanders calls out Hillary Clinton to announce her position on the Trans-Pacific Partnership (TPP) agreement; however, Hillary Clinton refuses to reveal her position, hoping that the agreement will be passed and she won't have to take a position. Continue reading →

This is one of the best interviews on American politics ever to be broadcasted. Ralph Nader and Jill Stein discuss our corrupt government and corrupt media controlled by corporations, and explain how we no longer have a democracy but corporate tyranny. Continue reading →

"And you know, we have to stop looking beyond this election cycle and see that this corporate driven ideology, you know, this commodification of the culture, this constant extracting of blood from us as citizens to pay what in essence were private debts of the banks which engaged in casino capitalism, has political consequences. History has taught us that. And Hillary Clinton is only going to further that process." Continue reading →

Questions surrounding Hillary Clinton and the Clinton Foundation continue to grow. On Sunday, Democratic National Committee interim chairperson Donna Brazile defended Clinton’s meetings as secretary of state with Clinton Foundation donors, saying, "When Republicans meet with their donors, with their supporters, their activists, they call it a meeting. When Democrats do that, they call it a conflict." Donna Brazile’s comments come in response to an Associated Press investigation revealing that while Hillary Clinton served as secretary of state, more than half of the private citizens she met with during the reporting period had donated to the Clinton Foundation. The AP investigation comes after a three-year battle to gain access to State Department calendars. The analysis shows that at least 85 of 154 people Hillary Clinton had scheduled phone or in-person meetings with were foundation donors. We speak to Pulitzer Prize-winning journalist Glenn Greenwald of The Intercept. His most recent piece is headlined "Why Did the Saudi Regime and Other Gulf Tyrannies Donate Millions to the Clinton Foundation?" Continue reading →

The Brainwashing Of Hillary Voters Is Complete. Hillary Clinton voters are either getting paid or have been brainwashed into defending her pro-corporate status quo policies. Jimmy Dore breaks it down on his broadcast, October 20, 2016. Continue reading →

There's got to be a reason for the Democrats to suppose to exist. And the reason the Democrats are supposed to exist is to be an opposition party to the Republicans. If you're in bed with the same people, taking money from the same people, you're no longer an opposition party. There's no reason for you to exist. And guess what? Don't be surprised that people don't vote for you. Continue reading →

IBM today announced its Health Cloud and Watson cognitive computing capabilities will support health data entered by customers in iOS apps using Apple's ResearchKit and HealthKit frameworks. The move, which complements IBM’s new Watson Health business unit, will arm medical researchers with a secure, open data storage solution, as well as access to IBM’s most sophisticated data analytics capabilities.

ISS, ISS A/S, a leading global provider of facility services, has signed a commercial agreement with IBM to use the power of Watson IoT to transform the management of over 25,000 buildings around the world.

IBM today announced that Faurecia, one of the world’s leading automotive suppliers, has selected IBM Cloud as a support of a major business transformation designed to accelerate digital manufacturing.

IBM and AOS, - a Colombian company specializing in providing business solutions- today announced they are collaborating to create a solution to enhance efficiency in the logistics and transport industry throughout the country, built on IBM Blockchain and Watson IoT on the IBM Cloud.

IBM today announced an expansion of its mobile portfolio for enterprises as it continues to create analytics-driven and cognitive enabled enterprise iOS apps that enable organizations to accelerate digital reinvention and transform how businesses engage across industries.

IBM today announced plans to acquire Promontory Financial Group, a global market-leading risk management and regulatory compliance consulting firm. Upon close, the capabilities of Promontory combined with IBM's deep industry expertise and Watson’s cognitive capabilities will directly address the massive operational effort and manual cost of escalating regulation and risk management requirements.

IBM and Box today announced a global partnership that will combine the best-in-class technologies and resources of both companies to transform work in the cloud. Together, the companies plan to integrate their existing products and services and develop new, innovative solutions targeted across industries and professions ranging from medical teams working on complex cases to individuals negotiating consumer loans by mobile phone to engineers and researchers identifying patterns in patents, reports and academic journals.

IBM today announced that M-Industry, one of the world’s largest private label consumer goods company and subsidiary of Switzerland’s largest retailer and supermarket chain, Migros Group, has launched a new IBM designed mobile offering to transform how product promoters work.

IBM today announced sweeping advances in its all-flash storage solutions and software to significantly drive down the costs of data and extend its solutions for hybrid and private cloud environments.

IBM today announced a research collaboratory in Singapore, where researchers from IBM intend to collaborate with scientists and engineers from public agencies in Singapore to improve the quality of its urban services. The focus of this research effort will be to use sensor networks to more effectively model, predict and manage the use of natural and physical infrastructure resources – water, transport and energy.  

Twitter and IBM today announced a landmark partnership that will help transform how businesses and institutions understand their customers, markets and trends – and inform every business decision. The alliance brings together Twitter data that distinctively represents the public pulse of the planet with IBM’s industry-leading cloud-based analytics, customer engagement platforms, and consulting services.

El actual entorno tecnológico impulsa a las empresas a transformar sus modelos de negocio en un escenario en donde, según la Organización para la Cooperación y el Desarrollo Económicos (OCDE), el 25% de la economía mundial será digital en los próximos cinco años. De esta forma, el uso de nuevas tecnologías se vuelve la pieza clave para asegurar tanto competitividad, como su alto desempeño.

IBM anunció hoy la primera plataforma de servicios basada en IBM Watson y construida en IBM Cloud para aumentar la inteligencia humana y ayudar a mejorar las operaciones de los proveedores de servicios a través de tecnologías cognitivas.

El Grupo BBVA acaba de formalizar un acuerdo con IBM para que esta firma asuma la operación y transformación de la infraestructura tecnológica actual de BBVA y el procesamiento de datos en América Latina y EE.UU., actualmente gestionada por su filial ATA en México.

Como parte de su compromiso por contribuir con la tecnología más innovadora a la resolución de los desafíos y retos que enfrenta el mundo, IBM dio a conocer que seleccionó a CUCEA (Centro Universitario de Ciencias Económico y Administrativas) de la Universidad de Guadalajara (UdeG); a fin de poner en marcha en México la implementación del Programa IBM Skills Academy, con foco en competencias de tecnología de Nube.

IBM anuncia el lanzamiento de IBM Cloud Private, una plataforma de software creada para los clientes que requieren la flexibilidad y capacidad de una nube pública en un ambiente privado. IBM Cloud Private transforma los sistemas de TI (Tecnologías de la Información) en un ambiente de nube flexible para crear un puente hasta las nubes públicas y acelerar el desarrollo de aplicativos.

IBM (NYSE: IBM) reinventa hoy el correo electrónico empresarial con una nueva oferta de colaboración social freemium que utiliza la tecnología de analítica integrada para dar a los empleados una nueva forma de conversar, encontrar a las personas y la información correcta rápidamente, y hacer su trabajo de manera eficiente. IBM Verse es el resultado de una inversión de US$100 millones en diseño e innovación, y reúne las plataformas líderes cloud, analytics, social y de seguridad de la compañía para transformar el futuro del trabajo.

IBM today announced that Westpac New Zealand, part of one of the world’s largest financial services institutions, has selected IBM’s private cloud technology to support its goal to be New Zealand’s leading digital bank. The new five year agreement is part of an extensive services and technology contract which includes Westpac migrating some of its business critical IT systems into IBM’s state-of-the-art Auckland data centre, enabling enhanced customer service.

IBM dio a conocer que el Tecnológico de Monterrey está transformando la gestión del entorno laboral de todas sus unidades de negocios con su solución de gestión de talento, Kenexa. La solución permite a los profesionales de Talento y Cultura (Recursos Humanos) del Tecnológico de Monterrey, tomar decisiones estratégicas a fin de impulsar los resultados de negocio basadas en hechos, es decir, sobre la base del análisis de talento (reporteadores) de su tradicional encuesta de clima organizacional.

Diltex -empresa mexicana propietaria de las marcas Ilusión y Fiorentina, socios de Vanity Fair Brands y franquiciatarios de David's Bridal en México- e IBM, anunciaron que la compañía dedicada a la industria de la moda está mejorando la experiencia del cliente y fortaleciendo su producción, distribución y comercialización a través de su transformación digital.

CEMEX, S.A.B. de C.V. (BMV: CEMEXCPO), una de las compañías de materiales para la industria de la construcción líder en el mundo, e IBM (NYSE: IBM) anunciaron hoy que CEMEX llevará a cabo una importante transformación tecnológica diseñada para optimizar sus operaciones, mejorar notablemente la experiencia de sus clientes y aumentar la eficiencia del negocio.

Durante la cumbre Business Connect 2017 en la Ciudad de México, IBM presentó a la Transformación Digital como una de las áreas de mayor crecimiento para los negocios en 2017 y mostró cómo las soluciones cognitivas (de analítica avanzada, de nube, de engagement), están transformando la forma en la que trabajamos y vivimos.

Las estrategias de negocio con las que organizaciones líderes están transformando su negocio para obtener mayores eficiencias se basan en tecnologías para mejorar el manejo de la información, la interacción con clientes y modelos de negocio en la nube. Estas tecnologías son impulsadas por IBM, reconociendo las necesidades de las compañías mexicanas.

IBM today announced new systems highly-tuned and optimised to help clients more quickly draw insights from vast amounts of data to anticipate emerging business trends, capture new opportunities and avoid risks. These new optimised systems support all environments in a data center, enabling clients to handle higher volumes of transactions and analyse data where it resides.

Tres proyectos que proponen mejorar la interacción y la experiencia de los jóvenes usuarios con servicios bancarios móviles, fueron reconocidos hoy por Banorte, IBM y el Tec de Monterrey como resultado del Reto Banorte en el marco de la Semana i, que la institución educativa llevó a cabo del 21 al 25 de septiembre en todo el país.

GIG Desarrollos Inmobiliarios dio a conocer que está utilizando una solución de analítica de datos de IBM para transformar el área de ventas inmobiliarias. La herramienta les ha permitido acelarar hasta 6 veces el tiempo dedicado al procesamiento de datos para el cálculo de comisiones.

IBM y VON DER HEIDE, compañía especializada en servicios de consultoría de Recursos Humanos, informan que han firmado una importante alianza para expandir su oferta de servicios de Employee Engagement y HR Analytics en toda América Latina. Por medio de las tecnologías de IBM, esta alianza le permitirá a VON DER HEIDE brindar a sus clientes una oferta de consultoría única en el mercado, para transformar estrategias de talento en resultados de negocio.

Vodafone New Zealand, a leading telecommunications services provider, and IBM (NYSE: IBM) today announced a partnership to deliver the Digital Vodafone 2021 program in New Zealand. The vision for Digital Vodafone 2021 is to create the most engaging digital customer experience by adopting agile as a way of working, embracing new technologies and simplifying business models. The program is supported by IBM iX, one of the world’s largest digital agencies and global business design partners.

IBM (NYSE: IBM) et SAP SE (NYSE: SAP) annoncent aujourd’hui des projets communs pour accompagner leurs clients dans la modernisation de leurs systèmes et processus afin d’accélérer leur présence dans l’économie numérique. Les deux compagnies envisagent particulièrement d’innover ensemble pour créer de nouvelles solutions qui augmentent la valeur ajoutée du client en s’appuyant sur des extensions cognitives, des expériences client et utilisateur renforcées ainsi que des fonctionnalités sectorielles. Tout ceci doté de la SAP® Business Suite, du logiciel 4 SAP HANA® (SAP S/4HANA) et disponible sur site et dans le Cloud.

Les deux sociétés s'unissent afin de redéfinir le travail quotidien de millions de personnes

@IBM et Hardis Group signent un accord mondial pour transformer la chaîne logistique à l'heure du #client connecté #smartercommerce

lior Banque annonce aujourd’hui avoir choisi l’application IBM MobileFirst sur iOS pour apporter une transformation fondamentale à la façon dont les clients en Pologne interagissent avec leur banque. A l’aide d’un iPad, les professionnels des services bancaires pourront fournir une expérience plus dynamique et personnalisée aux clients en tirant avantage de la puissance de l’analyse prédictive, et ce de façon sécurisée, facile, rapide et disponible 24h/24.

ANZ, Commonwealth Bank, IBM Scentre Group and Westpac have jointly launched a live pilot for Lygon, a new digital platform using blockchain technology to transform the way businesses obtain and manage bank guarantees that are often required as part of a retail property lease.

IBM (NYSE: IBM) today announced it has partnered with academia, government and industry to launch the Smart Transport Research Centre (STRC) based at Queensland University of Technology (QUT), which is being opened today by the Minister for Transport, the honourable Annastacia Palasczuk. IBM will contribute its global consulting expertise and technology in developing smarter traffic solutions to help make Australia’s transportation infrastructure smarter, improve commuter experiences and reduce environmental impact.

Icon Group first in Australia to adopt world-leading technology as part of its comprehensive cancer care offering

Lingmo’s Translate One2One uses IBM Watson Artificial Intelligence technology to translate in natural language.