Notch activates Wnt-4 signalling to control medio-lateral patterning of the pronephros

Previous studies have highlighted a role for the Notch signalling pathway during pronephrogenesis in the amphibian Xenopus laevis, and in nephron development in the mammalian metanephros, yet a mechanism for this function remains elusive. Here, we further the understanding of how Notch signalling patterns the early X. laevis pronephros anlagen, a function that might be conserved in mammalian nephron segmentation. Our results indicate that early phase pronephric Notch signalling patterns the medio-lateral axis of the dorso-anterior pronephros anlagen, permitting the glomus and tubules to develop in isolation. We show that this novel function acts through the Notch effector gene hrt1 by upregulating expression of wnt4. Wnt-4 then patterns the proximal pronephric anlagen to establish the specific compartments that span the medio-lateral axis. We also identified pronephric expression of lunatic fringe and radical fringe that is temporally and spatially appropriate for a role in regulating Notch signalling in the dorso-anterior region of the pronephros anlagen. On the basis of these results, along with data from previous publications, we propose a mechanism by which the Notch signalling pathway regulates a Wnt-4 function that patterns the proximal pronephric anlagen

Non-classical photon streams using rephased amplified spontaneous emission

We present a fully quantum mechanical treatment of optically rephased photon echoes. These echoes exhibit noise due to amplified spontaneous emission, however this noise can be seen as a consequence of the entanglement between the atoms and the output light. With a rephasing pulse one can get an "echo" of the amplified spontaneous emission, leading to light with nonclassical correlations at points separated in time, which is of interest in the context of building wide bandwidth quantum repeaters. We also suggest a wideband version of DLCZ protocol based on the same ideas.Comment: 5 pages, 4 figures. Added section

Experimental realization of light with time separated correlations by rephasing amplified spontaneous emission

Amplified spontaneous emission is a common noise source in active optical systems, it is generally seen as being an incoherent process. Here we excite an ensemble of rare earth ion dopants in a solid with a {\pi}-pulse, resulting in amplified spontaneous emission. The application of a second {\pi}-pulse leads to a coherent echo of the amplified spontaneous emission that is correlated in both amplitude and phase. For small optical thicknesses, we see evidence that the amplified spontaneous emission and its echo are entangled.Comment: 6 pages, 5 figures, the supplementary information pdf was uploaded with latex source files. This version accepted for publication in PR

Quantum simulation of the wavefunction to probe frustrated Heisenberg spin systems

Quantum simulators are controllable quantum systems that can reproduce the dynamics of the system of interest, which are unfeasible for classical computers. Recent developments in quantum technology enable the precise control of individual quantum particles as required for studying complex quantum systems. Particularly, quantum simulators capable of simulating frustrated Heisenberg spin systems provide platforms for understanding exotic matter such as high-temperature superconductors. Here we report the analog quantum simulation of the ground-state wavefunction to probe arbitrary Heisenberg-type interactions among four spin-1/2 particles . Depending on the interaction strength, frustration within the system emerges such that the ground state evolves from a localized to a resonating valence-bond state. This spin-1/2 tetramer is created using the polarization states of four photons. The single-particle addressability and tunable measurement-induced interactions provide us insights into entanglement dynamics among individual particles. We directly extract ground-state energies and pair-wise quantum correlations to observe the monogamy of entanglement

Ovine pedomics : the first study of the ovine foot 16S rRNA-based microbiome

We report the first study of the bacterial microbiome of ovine interdigital skin based on 16S rRNA by pyrosequencing and conventional cloning with Sanger-sequencing. Three flocks were selected, one a flock with no signs of footrot or interdigital dermatitis, a second flock with interdigital dermatitis alone and a third flock with both interdigital dermatitis and footrot. The sheep were classified as having either healthy interdigital skin (H), interdigital dermatitis (ID) or virulent footrot (VFR). The ovine interdigital skin bacterial community varied significantly by flock and clinical condition. The diversity and richness of operational taxonomic units was greater in tissue from sheep with ID than H or VFR affected sheep. Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria were the most abundant phyla comprising 25 genera. Peptostreptococcus, Corynebacterium and Staphylococcus were associated with H, ID and VFR respectively. Sequences of Dichelobacter nodosus, the causal agent of ovine footrot, were not amplified due to mismatches in the 16S rRNA universal forward primer (27F). A specific real time PCR assay was used to demonstrate the presence of D. nodosus which was detected in all samples including the flock with no signs of ID or VFR. Sheep with ID had significantly higher numbers of D. nodosus (104-109 cells/g tissue) than those with H or VFR feet

Phase II trial of Modified Vaccinia Ankara (MVA) virus expressing 5T4 and high dose Interleukin-2 (IL-2) in patients with metastatic renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Interleukin-2 (IL-2) induces durable objective responses in a small cohort of patients with metastatic renal cell carcinoma (RCC) but the antigen(s) responsible for tumor rejection are not known. 5T4 is a non-secreted membrane glycoprotein expressed on clear cell and papillary RCCs. A modified vaccinia virus Ankara (MVA) encoding 5T4 was tested in combination with high-dose IL-2 to determine the safety, objective response rate and effect on humoral and cell-mediated immunity.</p> <p>Methods</p> <p>25 patients with metastatic RCC who qualified for IL-2 were eligible and received three immunizations every three weeks followed by IL-2 (600,000 IU/kg) after the second and third vaccinations. Blood was collected for analysis of humoral, effector and regulatory T cell responses.</p> <p>Results</p> <p>There were no serious vaccine-related adverse events. While no objective responses were observed, three patients (12%) were rendered disease-free after nephrectomy or resection of residual metastatic disease. Twelve patients (48%) had stable disease which was associated with improved median overall survival compared to patients with progressive disease (not reached vs. 28 months, p = 0.0261). All patients developed 5T4-specific antibody responses and 13 patients had an increase in 5T4-specific T cell responses. Although the baseline frequency of Tregs was elevated in all patients, those with stable disease showed a trend toward increased effector CD8+ T cells and a decrease in Tregs.</p> <p>Conclusion</p> <p><b>V</b>accination with MVA-5T4 did not improve objective response rates of IL-2 therapy but did result in stable disease associated with an increase in the ratio of 5T4-specific effector to regulatory T cells in selected patients.</p> <p>Trial registration number</p> <p>ISRCTN83977250</p

Measuring Patient and Clinician Perspectives to Evaluate Change in Health-Related Quality of Life Among Patients with Chronic Obstructive Pulmonary Disease

CONTEXT: Many treatments aim to improve patients’ health-related quality of life (HRQoL), and many care guidelines suggest assessing symptoms and their impact on HRQoL. However, there is a lack of consensus regarding which HRQoL outcome measures are appropriate to assess, and how much change on those measures depict significant HRQoL improvement. OBJECTIVE: We used triangulation methods to identify and understand clinically important differences (CIDs) for the amount of change in HRQoL that reflects both health professionals and patients’ values, among patients with chronic obstructive pulmonary disease (COPD). DESIGN, SETTING, AND PARTICIPANTS: We incorporated three perspectives: (1) an expert panel of physicians familiar with the measurement of HRQoL in COPD patients; (2) 610 primary care COPD outpatients who completed baseline and bimonthly follow-up HRQoL interviews over the 12-month study; and (3) the primary care physicians (PCPs; n = 43) of these outpatients who assessed their patients’ disease at baseline and at subsequent PCP visits during the year long study. MEASUREMENTS: The Chronic Respiratory Disease Questionnaire (CRQ), the Medical Outcomes Study Short Form 36-item survey (SF-36, version 2.0), and global assessments of change from each of the three perspectives for all HRQoL domains. RESULTS: With few exceptions, the CRQ was able to detect small changes at levels reported by the patients (1–2 points) and their PCPs (1–5 points). These results confirm minimal important difference standards developed in 1989 by Jaeschke et al. anchored on patient-perceived changes in HRQoL. In general, the expert panel and PCP CIDs were larger than the patient CIDs. CONCLUSION: This triangulation methodology yielded improved interpretation, understanding, and insights on stakeholder perspectives of CIDs for patient-reported outcomes

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

State-building, war and violence : evidence from Latin America

In European history, war has played a major role in state‐building and the state monopoly on violence. But war is a very specific form of organized political violence, and it is decreasing on a global scale. Other patterns of armed violence now dominate, ones that seem to undermine state‐building, thus preventing the replication of European experiences. As a consequence, the main focus of the current state‐building debate is on fragility and a lack of violence control inside these states. Evidence from Latin American history shows that the specific patterns of the termination of both war and violence are more important than the specific patterns of their organization. Hence these patterns can be conceptualized as a critical juncture for state‐building. While military victories in war, the subordination of competing armed actors and the prosecution of perpetrators are conducive for state‐building, negotiated settlements, coexistence, and impunity produce instability due to competing patterns of authority, legitimacy, and social cohesion