We investigated the use of adoptively transferred donor-derived cytomegalovirus (CMV) specific cytotoxic T lymphocytes (CTL) as immune reconstitution postallogeneic transplant in a phase 2 study. ...Fifty patients were infused with a single dose of 2 × 107cells/m2 after day 28 post-transplant. Twenty-six patients reactivated CMV posttransplant (only 5 post-CTL infusion) and 9 required therapy with ganciclovir or foscarnet (only 1 post-CTL infusion). There was 1 case of fatal CMV disease, attributable to high levels of antithymocyte globulin at the time of T cell infusion. We compared the patients in the phase 2 study with a group of contemporaneous controls also treated at the trial centers. There was no increase in acute or chronic graft-versus-host disease attributable to CTL infusion; overall and progression-free survival were similar in both groups. There was a reduction in the percentage of patients who required CMV directed antiviral therapy (17% vs 36%, P = .01) and in the total number of treatment days in the cohort receiving CTL (3.4 days vs 8.9 days, P = .03) without a reduction in CMV reactivation rates. We postulate that adoptively transferred cells are able to expand in response to viral antigen, limit viral replication, and prevent progression to tissue infection. This study was registered on the Australian Clinical Trial Registry as #ACTRN12605000213640 and #ACTRN12607000224426.
•Infusion of CMV-specific T cells early posttransplant does not increase acute or chronic graft-versus-host disease.•CMV-specific T cells early posttransplant reduce the need for pharmacotherapy without increased rates of CMV-related organ damage.
Molecular motors employ chemical energy to generate unidirectional mechanical output against a track while navigating a chaotic cellular environment, potential disorder on the track, and against ...Brownian motion. Nevertheless, decades of nanometer-precise optical studies suggest that myosin-5a, one of the prototypical molecular motors, takes uniform steps spanning 13 subunits (36 nm) along its F-actin track. Here, we use high-resolution interferometric scattering microscopy to reveal that myosin takes strides spanning 22 to 34 actin subunits, despite walking straight along the helical actin filament. We show that cumulative angular disorder in F-actin accounts for the observed proportion of each stride length, akin to crossing a river on variably spaced stepping stones. Electron microscopy revealed the structure of the stepping molecule. Our results indicate that both motor and track are soft materials that can adapt to function in complex cellular conditions.
For poikilothermic organisms in aquatic environment, temperature strongly affects metabolism and modulates the extent to which it is mass transfer limited. The effects of temperature on metabolism ...are translated into organism performance depending on the organism size, morphology, and the flow regime to which they are exposed. Environmental forcing of metabolism is particularly germane to tropical reef corals, because they increasingly are exposed to upward temperature perturbations to which they display variable responses that remain incompletely understood. In this study, we tested the effects of colony size and seawater turbulence on the response of the common Indo-Pacific branching coral,
Pocillopora verrucosa
, to different seawater temperatures. Using whole-colony calcification as a response variable, 12 tanks (each 150 l) were used in two trials lasting 14 days to contrast the effects of seawater turbulence (two levels) and temperature (25.5 vs 29.5 °C) on colonies varying in size from ~ 4 to 13-cm diameter. Turbulence in the tanks was measured as the root mean square (rms) turbulent flow speed (
q
rms
), which quantified the variation in speed of complex and non-linear flow, regardless of direction. Treatments contrasted low (
q
rms
= 0.63 cm s
−1
) and high (
q
rms
= 2.07 cm s
−1
) turbulence that were ecologically relevant for shallow coral reefs. The effects of turbulent flow speed and temperature on calcification (mg day
−1
) differed among colony sizes: at 25.5 °C, calcification increased with tissue surface area at a slower rate under high, compared to low turbulent flow speeds; at low turbulent flow speeds, calcification increased with tissue surface area more slowly at 29.5 versus 25.5 °C. These results show that the response of branching corals to temperatures depends on colony size and turbulent flow speed. This outcome suggests that spatial heterogeneity in turbulent flow regimes across a coral reef may provide opportunities for branching corals to exploit colony size to modulate susceptibility to rising temperature.
We present a capture-based approach for bisulfite-converted DNA that allows interrogation of pre-defined genomic locations, allowing quantitative and qualitative assessments of 5-methylcytosine (5mC) ...and 5-hydroxymethylcytosine (5hmC) at CG dinucleotides and in non-CG contexts (CHG, CHH) in mammalian and plant genomes. We show the technique works robustly and reproducibly using as little as 500 ng of starting DNA, with results correlating well with whole genome bisulfite sequencing data, and demonstrate that human DNA can be tested in samples contaminated with microbial DNA. This targeting approach will allow cell type-specific designs to maximize the value of 5mC and 5hmC sequencing.
Phosphoinositide 3-kinase α (PI3Kα) is a critical regulator of cell growth and transformation, and its signaling pathway is the most commonly mutated pathway in human cancers. The mammalian target of ...rapamycin (mTOR), a class IV PI3K protein kinase, is also a central regulator of cell growth, and mTOR inhibitors are believed to augment the antiproliferative efficacy of PI3K/AKT pathway inhibition. 2,4-Difluoro-N-{2-(methyloxy)-5-4-(4-pyridazinyl)-6-quinolinyl-3-pyridinyl}benzenesulfonamide (GSK2126458, 1) has been identified as a highly potent, orally bioavailable inhibitor of PI3Kα and mTOR with in vivo activity in both pharmacodynamic and tumor growth efficacy models. Compound 1 is currently being evaluated in human clinical trials for the treatment of cancer.
While critical security studies largely concentrates on objects of security, this book focuses on the subject position from which ‘securitization’ and other security practices take place.
First , it ...argues that the modern subject itself emerges and is sustained as a function of security and insecurity. It suggests, consequently, that no analytic frame can produce or reproduce the subject in some original or primordial form that does not already reproduce a fundamental or structural insecurity. It critically returns, through a variety of studies, to traditionally held conceptions of security and insecurity as simple predicates or properties that can be associated or not to some more essential, more primeval, more true or real subject. It thus opens and explores the question of the security of the subject itself, locating, through a reconstruction of the foundations of the concept of security, in the modern conception of the subject, an irreducible insecurity.
Second , it argues that practices of security can only be carried out as a certain kind of negotiation about values . The analyses in this book find security expressed again and again as a function of value cast in terms of an explicit or implicit philosophy of life, of culture, of individual and collective anxieties and aspirations, of expectations about what may be sacrificed and what is worth preserving. By way of a critical examination of the value function of security, this book discovers the foundation of values as dependent on a certain management of their own vulnerability, continuously under threat, and thus fundamentally and necessarily insecure.
This book will be an indispensible resource for students of Critical Security Studies, Political Theory, Philosophy, Ethics and International Relations in general.
J. Peter Burgess is Research Professor at PRIO, the Peace Research Institute Oslo, where he leads the Security Programme and edits the interdisciplinary peer-reviewed journal Security Dialogue , and Senior Research Fellow at the Institute for European Studies of the Vrije Universiteit Brussels.
Introduction: Security as Ethos and Episteme Part 1: Theory of the Ethical Subject 1. Nietzsche, or Value and the Subject of Security 2. Foucault, or Genealogy of the Ethical Subject 3. Lacan, or the Ethical Subject of the Real 4. Butler, or the Precarious Subject Part 2: Holding Together 5. Identity, Community and Security 6. Insecurity of the European Community of Values 7. Psychoanalysis of the National Thing 8. Security Clture and the New Ethos of Risk 9. Intolerable Insecurity Part 3: Geopolitical Rationalities of Europe 10. The Modernity of a Cosmopolitan Europe 11. The New Nomos of Europe 12. A Federalist Europe between Economic and Cultural Value 13. Justice in Political, Legal and Moral Community 14. War in the Name of Europe and the Legitimacy of Collective Violence. Conclusion: The Many Faces of European Security
This qualitative study examined parents' experiences of supporting their children during the COVID-19 pandemic. Eighteen parents of children aged 2-16 years from diverse backgrounds, living in the ...UK, were interviewed one-to-one about their experiences. Ten professionals working with children and families were also interviewed to gain a broader perspective of parents' experiences. Using Reflexive Thematic Analysis, four themes were developed: (a) worries and uncertainties; (b) mental exhaustion; (c) resources available to cope with the challenges; and (d) finding the positives. Findings revealed the worries and uncertainties that parents faced regarding how best to support their child and the long-term consequences of the pandemic, as well as feelings of mental exhaustion from juggling multiple responsibilities. The impact of COVID-19 on parents' wellbeing was varied and parents identified several factors that determined their ability to support their children, such as space in the home environment, support networks and their personal mental health. Despite the challenges, some parents reported positive experiences, such as strengthened family bonds during the pandemic. Our study emphasizes the importance of flexible work arrangements and family-friendly employment policies, as well as support for parents to enable them to support their children and look after their own wellbeing.
Cultures of governance and peace Burgess, J. Peter; Richmond, Oliver P; Samaddar, Ranabir
2016, 2016., 20160910, 2016-09-10
eBook
This volume brings together insights which look at the intersection of governance, culture and conflict resolution in India and the European Union. Two very different but connected epistemic, ...cultural and institutional settings, which have been divided by distance, colonialism and culture; yet have recently been brought closer together by ideas and practices of what is known as liberal peace, neoliberal state and development projects. The differences are obvious in terms of geography, culture, the nature and shape of institutions, and historical forces: and yet the commonalities between the two are surprising. This is the first book to compare contemporary Indian and European Union approaches to peace and is based on strong case studies and rigorous analysis. Postgraduate students, peace and conflict researchers, policy-makers and practitioners will benefit immensely from insights provided in this book.
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