Quantitative criteria for choosing targets and indicators for sustainable use of ecosystems

The authors thank Simon Greenstreet, Cristina Herbon, Simon Jennings, Tiziana Luisetti, Lucille Paltriguera, and Christian Wilson for comments on previous versions of this paper. This work has resulted from the DEVOTES (DEVelopment Of innovative Tools for understanding marine biodiversity and assessing Good Environmental Status) project funded by the EU under the 7th Framework Programme, ‘The Ocean of Tomorrow’ Theme (No. 308392), www.devotes-project.eu. Further, A.G.R. was partially funded by the Natural Environment Research Council and the UK Department for Food, Environment and Rural Affairs (Defra) within the Marine Ecosystems Research Program (MERP), C.P.L. by Defra (M1228), A.Z. by BIOsingle bondC3 within the joint Baltic Sea Research and Development Programme (EU 7th and Research Council of Lithuania, BONUS-1/2014), and M.C.U. by the Spanish Programme for talent and employability in I + D + i ‘Torres Quevedo’

Autoantibodies to muscarinic acetylcholine receptors found in patients with primary biliary cirrhosis

<p>Abstract</p> <p>Background</p> <p>Autoantibodies to the human muscarinic acetylcholine receptor of the M3 type (hmAchR M3) have been suggested to play an etiopathogenic role in Sjögren's syndrome. Primary biliary cirrhosis (PBC) often is associated with this syndrome. Therefore, we studied the co-presence of hmAchR M3 autoantibodies in patients with PBC.</p> <p>Methods</p> <p>Frequency of hmAchR M3 autoantibodies was assessed by Western blotting analysis as well as by an ELISA using a 25-mer peptide of the 2^ndextracellular loop of hmAchR M3. Co-localization of hmAchR M3/PBC-specific autoantibodies was studied by confocal laser scanning microscopy. Finally, sera from patients with PBC as well as from healthy controls were tested.</p> <p>Results</p> <p>Western blotting analysis as well as results from ELISA testing revealed a significantly enhanced IgG reactivity in PBC patients in contrast to healthy controls. Co-localization of autoantibodies with the hmAchR M3 receptor-specific autoantibodies was observed in 10 out of 12 PBC-patients but none of the 5 healthy controls. Antibodies of the IgM type were not found to be affected.</p> <p>Conclusions</p> <p>For the first time, our data demonstrate the presence of autoantibodies to the hmAchR M3 in PBC patients. These findings might contribute to the understanding of the pathogenesis of this disease. Further studies have to focus on the functionality of hmAchR M3 autoantibodies in PBC patients.</p

Efficacy and safety profile of boceprevir- or telaprevir-based triple therapy or dual peginterferon alfa-2a or alfa-2b plus ribavirin therapy in chronic hepatitis C: the real-world PegBase observational study.

BACKGROUND: The aim of the study was to determine the efficacy and safety of triple therapy with a first-generation protease inhibitor (PI; boceprevir, telaprevir) plus peginterferon alfa-2a or -2b plus ribavirin, and dual therapy (peginterferon alfa-2a or -2b plus ribavirin) in patients with chronic hepatitis C (CHC) in routine clinical practice. METHODS: PegBase was an international, prospective, observational study in which 4441 patients with CHC were enrolled in 27 countries. This analysis focuses on results in 4100 treatment-naïve and previously treated patients treated with PI-based triple therapy or dual therapy, according to the discretion of the investigator and local standards of practice. The primary efficacy outcome was sustained virological response after 12-week follow up (SVR12). RESULTS: SVR12 rates in treatment-naïve genotype (G) 1 patients were 56.6% and 62.9% for recipients of boceprevir plus peginterferon alfa-2a/ribavirin and boceprevir plus peginterferon alfa-2b/ribavirin, respectively, and 65.3% and 58.6% for recipients of telaprevir plus peginterferon alfa-2a/ribavirin and telaprevir plus peginterferon alfa-2b/ribavirin, respectively. In previously treated patients assigned to these four regimens, SVR12 rates were 43.6%, 48.3%, 60.3% and 56.1%, respectively. Among treatment-naïve patients assigned to peginterferon alfa-2a/ribavirin and peginterferon alfa-2b/ribavirin, respectively, SVR12 rates were 49.2% and 41.9% in G1 patients, 75.7% and 83.3% in G2 patients, 65.9% and 65.9% in G3 patients, and 49.7%, and 51.1% in G4 patients. The safety and tolerability of dual and triple therapy were consistent with previous reports. CONCLUSION: The efficacy and safety of first-generation PI-based triple-therapy and dual-therapy regimens in this real-world cohort were broadly comparable to those of previous studies.F. Hoffmann-La Roche Ltd., Basel, Switzerlan

Desensitizing Inflation from the Planck Scale

A new mechanism to control Planck-scale corrections to the inflationary eta parameter is proposed. A common approach to the eta problem is to impose a shift symmetry on the inflaton field. However, this symmetry has to remain unbroken by Planck-scale effects, which is a rather strong requirement on possible ultraviolet completions of the theory. In this paper, we show that the breaking of the shift symmetry by Planck-scale corrections can be systematically suppressed if the inflaton field interacts with a conformal sector. The inflaton then receives an anomalous dimension in the conformal field theory, which leads to sequestering of all dangerous high-energy corrections. We analyze a number of models where the mechanism can be seen in action. In our most detailed example we compute the exact anomalous dimensions via a-maximization and show that the eta problem can be solved using only weakly-coupled physics.Comment: 34 pages, 3 figures

Social interactions through the eyes of macaques and humans

Group-living primates frequently interact with each other to maintain social bonds as well as to compete for valuable resources. Observing such social interactions between group members provides individuals with essential information (e.g. on the fighting ability or altruistic attitude of group companions) to guide their social tactics and choice of social partners. This process requires individuals to selectively attend to the most informative content within a social scene. It is unclear how non-human primates allocate attention to social interactions in different contexts, and whether they share similar patterns of social attention to humans. Here we compared the gaze behaviour of rhesus macaques and humans when free-viewing the same set of naturalistic images. The images contained positive or negative social interactions between two conspecifics of different phylogenetic distance from the observer; i.e. affiliation or aggression exchanged by two humans, rhesus macaques, Barbary macaques, baboons or lions. Monkeys directed a variable amount of gaze at the two conspecific individuals in the images according to their roles in the interaction (i.e. giver or receiver of affiliation/aggression). Their gaze distribution to non-conspecific individuals was systematically varied according to the viewed species and the nature of interactions, suggesting a contribution of both prior experience and innate bias in guiding social attention. Furthermore, the monkeys’ gaze behavior was qualitatively similar to that of humans, especially when viewing negative interactions. Detailed analysis revealed that both species directed more gaze at the face than the body region when inspecting individuals, and attended more to the body region in negative than in positive social interactions. Our study suggests that monkeys and humans share a similar pattern of role-sensitive, species- and context-dependent social attention, implying a homologous cognitive mechanism of social attention between rhesus macaques and humans

Baryonic symmetries and M5 branes in the AdS_4/CFT_3 correspondence

We study U(1) symmetries dual to Betti multiplets in the AdS_4/CFT_3 correspondence for M2 branes at Calabi-Yau four-fold singularities. Analysis of the boundary conditions for vector fields in AdS_4 allows for a choice where wrapped M5 brane states carrying non-zero charge under such symmetries can be considered. We begin by focusing on isolated toric singularities without vanishing six-cycles, and study in detail the cone over Q^{111}. The boundary conditions considered are dual to a CFT where the gauge group is U(1)^2 x SU(N)^4. We find agreement between the spectrum of gauge-invariant baryonic-type operators in this theory and wrapped M5 brane states. Moreover, the physics of vacua in which these symmetries are spontaneously broken precisely matches a dual gravity analysis involving resolutions of the singularity, where we are able to match condensates of the baryonic operators, Goldstone bosons and global strings. We also argue more generally that theories where the resolutions have six-cycles are expected to receive non-perturbative corrections from M5 brane instantons. We give a general formula relating the instanton action to normalizable harmonic two-forms, and compute it explicitly for the Q^{222} example. The holographic interpretation of such instantons is currently unclear.Comment: 92 pages, 10 figure

D3-brane Potentials from Fluxes in AdS/CFT

We give a comprehensive treatment of the scalar potential for a D3-brane in a warped conifold region of a compactification with stabilized moduli. By studying general ultraviolet perturbations in supergravity, we systematically incorporate `compactification effects' sourced by supersymmetry breaking in the compact space. Significant contributions to the D3-brane potential, including the leading term in the infrared, arise from imaginary anti-self-dual (IASD) fluxes. For an arbitrary Calabi-Yau cone, we determine the most general IASD fluxes in terms of scalar harmonics, then compute the resulting D3-brane potential. Specializing to the conifold, we identify the operator dual to each mode of flux, and for chiral operators we confirm that the potential computed in the gauge theory matches the gravity result. The effects of four-dimensional curvature, including the leading D3-brane mass term, arise directly from the ten-dimensional equations of motion. Furthermore, we show that gaugino condensation on D7-branes provides a local source for IASD flux. This flux precisely encodes the nonperturbative contributions to the D3-brane potential, yielding a promising ten-dimensional representation of four-dimensional nonperturbative effects. Our result encompasses all significant contributions to the D3-brane potential discussed in the literature, and does so in the single coherent framework of ten-dimensional supergravity. Moreover, we identify new terms with irrational scaling dimensions that were inaccessible in prior works. By decoupling gravity in a noncompact configuration, then systematically reincorporating compactification effects as ultraviolet perturbations, we have provided an approach in which Planck-suppressed contributions to the D3-brane effective action can be computed.Comment: 70 page

Holomorphic variables in magnetized brane models with continuous Wilson lines

We analyze the action of the target-space modular group in toroidal type IIB orientifold compactifications with magnetized D-branes and continuous Wilson lines. The transformation of matter fields agree with that of twisted fields in heterotic compactifications, constituting a check of type I/heterotic duality. We identify the holomorphic N = 1 variables for these compactifications. Matter fields and closed string moduli are both redefined by open string moduli. The redefinition of matter fields can be read directly from the perturbative Yukawa couplings, whereas closed string moduli redefinitions are obtained from D-brane instanton superpotential couplings. The resulting expressions reproduce and generalize, in the presence of internal magnetic fields, previous results in the literature.Comment: 9 pages, no figures; v2: conventions for Wilson lines changed, major simplifications in expressions, discussions extended, typos corrected, some references adde

Explicit de Sitter Flux Vacua for Global String Models with Chiral Matter

We address the open question of performing an explicit stabilisation of all closed string moduli (including dilaton, complex structure and Kaehler moduli) in fluxed type IIB Calabi-Yau compactifications with chiral matter. Using toric geometry we construct Calabi-Yau manifolds with del Pezzo singularities. D-branes located at such singularities can support the Standard Model gauge group and matter content. In order to control complex structure moduli stabilisation we consider Calabi-Yau manifolds which exhibit a discrete symmetry that reduces the effective number of complex structure moduli. We calculate the corresponding periods in the symplectic basis of invariant three-cycles and find explicit flux vacua for concrete examples. We compute the values of the flux superpotential and the string coupling at these vacua. Starting from these explicit complex structure solutions, we obtain AdS and dS minima where the Kaehler moduli are stabilised by a mixture of D-terms, non-perturbative and perturbative alpha'-corrections as in the LARGE Volume Scenario. In the considered example the visible sector lives at a dP_6 singularity which can be higgsed to the phenomenologically interesting class of models at the dP_3 singularity.Comment: 49 pages, 5 figures; v2: references adde