Multiple Unit Pooled Umbilical Cord Blood is a Viable Source of Therapeutic Regulatory T Cells

BACKGROUND: Regulatory T cells (Treg) are potentially a useful therapeutic option for the treatment of immunopathological conditions including graft-versus-host disease. Umbilical cord blood (UCB) offers certain advantages over adult peripheral blood (APB) as a source of Treg for cellular therapy but yields far fewer Treg per unit. Pooling of Treg from multiple donors may overcome this challenge. METHODS: In this study, we assessed the in vitro and in vivo efficacy of multiple donor pooled UCB or APB-derived Treg. RESULTS: In vitro, pooled freshly isolated UCB-derived Treg were as suppressive as APB-derived Treg. However, in a mouse model of human skin allodestruction, pooled UCB-derived Treg were more potent at suppressing alloresponses and prolonging skin survival compared with pooled APB-derived Treg. Improved survival of UCB Treg in an in vivo cell survival assay and their lower expression of human leukocyte antigen-ABC suggested that lower immunogenicity may account for their superior efficacy in vivo. CONCLUSION: Multiple-unit UCB is therefore a viable source of human Treg for cellular therapy, and pooling of Treg from multiple donors offers a useful strategy for achieving required therapeutic doses

Being Blacklisted by China, And What Can Be Learned from It

Bloomberg, and more recently The Washington Post, have run stories about the visa problems of scholars who contributed to Xinjiang: China’s Muslim Borderland, a volume edited by Frederick Starr and published by M.E. Sharpe in 2004. The Bloomberg piece was exhaustively reported; the reporters who wrote it, Dan Golden and Oliver Staley, conducted interviews with Chinese as well as western participants in the episode, and all in all did a good job with a complicated story. Inevitably, however, the Bloomberg piece creates some misconceptions, and these are as likely to be reinforced as cleared up in news reports that build on it, as the Washington Post story of last weekend shows. Now seems the time both to correct the problematic aspects of the Bloomberg piece and also to discuss lessons we may take away from the entire episode. There are a couple of key issues involved. Of special importance to scholars of China: are you in danger of being banned for what you write? My answer below will be, “not really.” And for universities, grant agencies and other institutions involved in academic exchanges with China, the episode raises the question of what you should do in the face of official Chinese interference in curriculum, research, guest lectures or other academic matters. I will suggest that a strong and collective response, organized by institutions and not left to the affected scholars themselves, is imperative. The reason for such a response is not simply to help individual scholars get visas, but to make the point that academic exchange must be unhampered and reciprocal and to set the right tone for future academic interchange with China

Scallop swimming kinematics and muscle performance: modelling the effects of "within-animal" variation in temperature sensitivity

Escape behaviour was investigated in Queen scallops (Aequipecten opercularis) acclimated to 5, 10 or 15 degrees C and tested at their acclimation temperature. Scallops are active molluscs, able to escape from predators by jet-propelled swimming using a striated muscle working in opposition to an elastic hinge ligament. The first cycle of the escape response was recorded using high-speed video ( 250 Hz) and whole-animal velocity and acceleration determined. Muscle shortening velocity, force and power output were calculated using measurements of valve movement and jet area, and a simple biomechanical model. The average shortening speed of the adductor muscle had a Q(10) of 2.04, significantly reducing the duration of the jetting phase of the cycle with increased temperature. Muscle lengthening velocity and the overall duration of the clap cycle were changed little over the range 5 - 15 degrees C, as these parameters were controlled by the relatively temperature-insensitive, hinge ligament. Improvements in the average power output of the adductor muscle over the first clap cycle ( 222 vs. 139 W kg(-1) wet mass at 15 and 5 degrees C respectively) were not translated into proportional increases in overall swimming velocity, which was only 32% higher at 15 degrees C ( 0.37m s(-1)) than 5 degrees C (0.28 m s(-1))

The future of sovereignty in multilevel governance Europe: a constructivist reading

Multilevel governance presents a depiction of contemporary structures in EU Europe as consisting of overlapping authorities and competing competencies. By focusing on emerging non-anarchical structures in the international system, hence moving beyond the conventional hierarchy/anarchy dichotomy to distinguish domestic and international arenas, this seems a radical transformation of the familiar Westphalian system and to undermine state sovereignty. Paradoxically, however, the principle of sovereignty proves to be resilient despite its alleged empirical decline. This article argues that social constructivism can explain the paradox, by considering sovereign statehood as a process-dependent institutional fact, and by showing that multilevel governance can feed into this process

Balancing the benefits and risks of public–private partnerships to address the global double burden of malnutrition

Objective: Transnational food, beverage and restaurant companies, and their corporate foundations, may be potential collaborators to help address complex public health nutrition challenges. While UN system guidelines are available for private-sector engagement, non-governmental organizations (NGO) have limited guidelines to navigate diverse opportunities and challenges presented by partnering with these companies through public&ndash;private partnerships (PPP) to address the global double burden of malnutrition.Design: We conducted a search of electronic databases, UN system websites and grey literature to identify resources about partnerships used to address the global double burden of malnutrition. A narrative summary provides a synthesis of the interdisciplinary literature identified.Results: We describe partnership opportunities, benefits and challenges; and tools and approaches to help NGO engage with the private sector to address global public health nutrition challenges. PPP benefits include: raising the visibility of nutrition and health on policy agendas; mobilizing funds and advocating for research; strengthening food-system processes and delivery systems; facilitating technology transfer; and expanding access to medications, vaccines, healthy food and beverage products, and nutrition assistance during humanitarian crises. PPP challenges include: balancing private commercial interests with public health interests; managing conflicts of interest; ensuring that co-branded activities support healthy products and healthy eating environments; complying with ethical codes of conduct; assessing partnership compatibility; and evaluating partnership outcomes.Conclusions: NGO should adopt a systematic and transparent approach using available tools and processes to maximize benefits and minimize risks of partnering with transnational food, beverage and restaurant companies to effectively target the global double burden of malnutrition.<br /

Progress in the Development of the 1 m Model of the 70 mm Aperture Quadrupole for the LHC Low-β\beta Insertions

Within the LHC magnet development program Oxford Instruments has built a one metre model of the 70 mm aperture low-beta quadrupole. The magnet features a four layer coil wound from two 8.2 mm wide graded NbTi cables, and is designed for 250 T/m at 1.9 K. The magnet has previously been tested between 4.5 K and 2.3 K. In this paper we review the magnet rebuild and the subsequent tests. Results on magnet training at 4.3 K and 1.9 K are presented along with the results related to quench protection studies.

A Real Space Description of Magnetic Field Induced Melting in the Charge Ordered Manganites: I. The Clean Limit

We study the melting of charge order in the half doped manganites using a model that incorporates double exchange, antiferromagnetic superexchange, and Jahn-Teller coupling between electrons and phonons. We primarily use a real space Monte Carlo technique to study the phase diagram in terms of applied field $(h)$ and temperature $(T)$, exploring the melting of charge order with increasing $h$ and its recovery on decreasing $h$. We observe hysteresis in this response, and discover that the `field melted' high conductance state can be spatially inhomogeneous even without extrinsic disorder. The hysteretic response plays out in the background of field driven equilibrium phase separation. Our results, exploring $h$, $T$, and the electronic parameter space, are backed up by analysis of simpler limiting cases and a Landau framework for the field response. This paper focuses on our results in the `clean' systems, a companion paper studies the effect of cation disorder on the melting phenomena.Comment: 16 pages, pdflatex, 11 png fig

Colossal magnetocapacitance and scale-invariant dielectric response in phase-separated manganites

Thin films of strongly-correlated electron materials (SCEM) are often grown epitaxially on planar substrates and typically have anisotropic properties that are usually not captured by edge-mounted four-terminal electrical measurements, which are primarily sensitive to in-plane conduction paths. Accordingly, the correlated interactions in the out-of-plane (perpendicular) direction cannot be measured but only inferred. We address this shortcoming and show here an experimental technique in which the SCEM under study, in our case a 600 Angstrom-thick (La1-yPry)0.67Ca0.33MnO3 (LPCMO) film, serves as the base electrode in a metal-insulator-metal (MIM) trilayer capacitor structure. This unconventional arrangement allows for simultaneous determination of colossal magnetoresistance (CMR) associated with dc transport parallel to the film substrate and colossal magnetocapacitance (CMC) associated with ac transport in the perpendicular direction. We distinguish two distinct strain-related direction-dependent insulator-metal (IM) transitions and use Cole-Cole plots to establish a heretofore unobserved collapse of the dielectric response onto a universal scale-invariant power-law dependence over a large range of frequency, temperature and magnetic field.Comment: 32 pages, 4 figures, Supplementary section included, Submitted to Nature Physic

Presupposition projection as proof construction

Even though Van der Sandt's presuppositions as anaphora approach is empirically successful, it fails to give a formal account of the interaction between world-knowledge and presuppositions. In this paper, an algorithm is sketched which is based on the idea of presuppositions as anaphora. It improves on this approach by employing a deductive system, Constructive Type Theory (CTT), to get a formal handle on the way world-knowledge influences presupposition projection. In CTT, proofs for expressions are explicitly represented as objects. These objects can be seen as a generalization of DRT's discourse markers. They are useful in dealing with presuppositional phenomena which require world-knowledge, such as Clark's bridging examples and Beaver's conditional presuppositions