Pre-existing virus-specific CD8+ T-cells provide protection against pneumovirus-induced disease in mice

Pneumoviruses such as pneumonia virus of mice (PVM), bovine respiratory syncytial virus (bRSV) or human (h)RSV are closely related pneumoviruses that cause severe respiratory disease in their respective hosts. It is well-known that T-cell responses are essential in pneumovirus clearance, but pneumovirus-specific T-cell responses also are important mediators of severe immunopathology. In this study we determined whether memory- or pre-existing, transferred virus-specific CD8 + T-cells provide protection against PVM-induced disease. We show that during infection with a sublethal dose of PVM, both natural killer (NK) cells and CD8 + T-cells expand relatively late. Induction of CD8 + T-cell memory against a single CD8 + T-cell epitope, by dendritic cell (DC)-peptide immunization, leads to partial protection against PVM challenge and prevents Th2 differentiation of PVM-induced CD4 T-cells. In addition, adoptively transferred PVM-specific CD8 + T-cells, covering the entire PVM-specific CD8 + T-cell repertoire, provide partial protection from PVM-induced disease. From these data we infer that antigen-specific memory CD8 + T-cells offer significant protection to PVM-induced disease. Thus, CD8 + T-cells, despite being a major cause of PVM-associated pathology during primary infection, may offer promising targets of a protective pneumovirus vaccine

Assessing the Impact of a Small-Group Behavioral Intervention on Sexual Behaviors Among Adolescent Girls and Young Women in Lilongwe Malawi: A Quasi-Experimental Cohort Study

Adolescent girls and young women (AGYW) in sub-Saharan Africa are at high risk of many adverse sexual and reproductive health outcomes. Small-group interventions addressing underlying vulnerabilities may influence risky sexual behaviors associated with these adverse outcomes. Girl Power-Malawi assessed whether a facilitator-led, curriculum-driven small-group behavioral intervention impacted risky sexual behaviors among AGYW in Lilongwe, Malawi. Four Health Centers were selected; two were randomly assigned to provide the intervention. Two-hundred fifty AGYW 15–24 years old were enrolled in each clinic (N = 1000 total), followed for 1 year, and interviewed at baseline and endline. At both time points participants reported on two behaviors in the last month (vaginal sex and ≥ 2 sexual partners) and two behaviors in the last year (age-disparate relationships and transactional relationships). In intervention clinics, there were no declines in risk behaviors between baseline and endline. Endline behaviors were not less risky in intervention clinics than control clinics. This intervention did not have a positive effect on four risk behaviors over a 1-year period

More light and less heat Mirowski on economics and the energy metaphor

I initially approached More Heat than Light with some apprehension. This is not because I suspected that I would disagree with its main thesis but because I feared that I would find the book anticlimactic. Over the past few years, Phil Mirowski has served us a number of delightful appetizers’-so many in fact that I suspected I might tire of the taste before the main entrée appeared. These concerns were wholly unfounded. The main entrée has finally arrived and is of such depth and complexity that it makes the appetizers, well, just appetizers. Mirowski’s central thesis is that neoclassical economics-initially developed during the 1870s and currently the dominant paradigm in economic theory-amounts to little more than a &dquo;brazen daylight robbery&dquo; (p. 4)2 of nineteenth-century energy physics. Motivated by the desire to achieve the status and prestige of the physical sciences, early neoclassical economists created their &dquo;revolution&dquo; by simply substituting &dquo;utility&dquo; for &dquo;energy&dquo; in the physics of their day. In a limited respect, this project was successful-the mathematical formalism of energy physics did (and does) contribute to the scientific respectability of the neoclassical research program-but this status was achieved at substantial cost. Mirowski argues that there were (and are) deep problems associated with the economic appropriation of the energy metaphor; physical systems have properties that make the mathematics appropriate, but these properties are not shared by economic systems. For example, the physical requirement that potential energy and kinetic energy sum to a constant translates into the economic requirement that utility and income sum to a constant. This is a problem because utility and income are measured in entirely different units. Mirowski argues that such difficulties were exacerbated by the scientific naivete of the early neoclassical economists who were trained in science and engineering-they had been exposed to the basic ideas of energy physics-but their knowledge was relatively rudimentary (p. 250). The result was energy physics appropriated in a &dquo;shoddy and slipshod manner&dquo; (p. 108). Mirowski provides a detailed discussion of how this misappropriation of the energy metaphor has surreptitiously influenced the development of modern economic thought. He reconstructs and explains certain generally accepted facts of theoretical life in economics (such as the problems of neoclassical production theory) and exposes some of the fundamental weaknesses of neoclassical theory (such as its inability to explain preference changes). Mirowski also argues that the dominance of the energy metaphor from nineteenth-century physics has prevented economists from taking advantage of more recent developments in physical theory, such as quantum mechanics and the theory of relativity. The result, according to Mirowski, is a tale reminiscent of Dorian Gray .... Neoclassicals, by imbibing some mystical elixir of modern mathematical techniques, have maintained the figure of vibrant youth, while hidden away somewhere in the attic is the real portrait, the original metaphor of a conserved preference field in an independently constituted commodity space, growing progressively desiccated and decrepit. (p. 374) My overall evaluation of Mirowski’s thesis is quite positive. I believe that he is entirely correct about the role of the energy metaphor in early neoclassical economics (probably reaching an apogee in Irving Fisher), and he is also correct that the metaphor has been lurking ever since in the background of neoclassical economics. The energy metaphor and its mathematics have been actively influential in the development of modem neoclassical theory, although I would probably weaken its impact from Mirowski’s story by saying &dquo;influenced&dquo; whereas Mirowski would say &dquo;dominated.&dquo; Where I mainly differ from Mirowski is on the implications of his thesis. For Mirowski, uncovering this hidden influence amounts to a scathing critique of modern neoclassical economics (and given the neoclassical dominance of the profession, this means most of modem economics). For him, the metaphor and its mathematics have been both dominant and pernicious. I disagree. While I am convinced that Mirowski has uncovered something important that can be used to further our understanding of the development of modem economic theory, I am not convinced that his thesis entails the kind of critical bite that he would like it to have. Given this overall evaluation of More Heat than Light, I will divide my comments into two sections. The first-more light-lends additional support to Mirowski’s general historical thesis by using it to illuminate two areas of modem neoclassical economics that Mirowski does not emphasize. The second-less heat-offers some arguments against Mirowski’s critical interpretation of his general thesis

Inhibition of TNF-α protects in vitro brain barrier from ischaemic damage

Cerebral ischaemia, associated with neuroinflammation and oxidative stress, is known to perturb blood–brain barrier (BBB) integrity and promote brain oedema formation. Using an in vitro model of human BBB composed of brain microvascular endothelial cells and astrocytes, this study examined whether suppression of TNF-α, a potent pro-inflammatory cytokine, might attenuate ischaemia-mediated cerebral barrier damage. Radical decreases in transendothelial electrical resistance and concomitant increases in paracellular flux across co-cultures exposed to increasing periods of oxygen-glucose deprivation alone (0.5–20 h) or followed by 20 h of reperfusion (OGD ± R) confirmed the deleterious effects of ischaemic injury on cerebral barrier integrity and function which concurred with reductions in tight junction protein (claudin-5 and occludin) expressions. OGD ± R elevated TNF-α secretion, NADPH oxidase activity, O2radical dot− production, actin stress fibre formation, MMP-2/9 activities and apoptosis in both endothelial cells and astrocytes. Increases in MMP-2 activity were confined to its extracellular isoform and treatments with OGD + R in astrocytes where MMP-9 could not be detected at all. Co-exposure of individual cell lines or co-cultures to an anti-TNF-α antibody dramatically diminished the extent of OGD ± R-evoked oxidative stress, morphological changes, apoptosis, MMP-2/9 activities while improving the barrier function through upregulation of tight junction protein expressions. In conclusion, vitiation of the exaggerated release of TNF-α may be an important therapeutic strategy in preserving cerebral integrity and function during and following a cerebral ischaemic attack

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Reducing heterotic M-theory to five dimensional supergravity on a manifold with boundary

This paper constructs the reduction of heterotic $M$-theory in eleven dimensions to a supergravity model on a manifold with boundary in five dimensions using a Calabi-Yau three-fold. New results are presented for the boundary terms in the action and for the boundary conditions on the bulk fields. Some general features of dualisation on a manifold with boundary are used to explain the origin of some topological terms in the action. The effect of gaugino condensation on the fermion boundary conditions leads to a `twist' in the chirality of the gravitino which can provide an uplifting mechanism in the vacuum energy to cancel the cosmological constant after moduli stabilisation.Comment: 16 pages, RevTe