Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking alphavbeta5 integrin.

Daily phagocytosis by the retinal pigment epithelium (RPE) of spent photoreceptor outer segment fragments is critical for vision. In the retina, early morning circadian photoreceptor rod shedding precedes synchronized uptake of shed photoreceptor particles by RPE cells. In vitro, RPE cells use the integrin receptor alphavbeta5 for particle binding. Here, we tested RPE phagocytosis and retinal function in beta5 integrin--deficient mice, which specifically lack alphavbeta5 receptors. Retinal photoresponses severely declined with age in beta5-/- mice, whose RPE accumulated autofluorescent storage bodies that are hallmarks of human retinal aging and disease. beta5-/- RPE in culture failed to take up isolated photoreceptor particles. beta5-/- RPE in vivo retained basal uptake levels but lacked the burst of phagocytic activity that followed circadian photoreceptor shedding in wild-type RPE. Rhythmic activation of focal adhesion and Mer tyrosine kinases that mediate wild-type retinal phagocytosis was also completely absent in beta5-/- retina. These results demonstrate an essential role for alphavbeta5 integrin receptors and their downstream signaling pathways in synchronizing retinal phagocytosis. Furthermore, they identify the beta5-/- integrin mouse strain as a new animal model of age-related retinal dysfunction

Powered bone marrow biopsy procedures produce larger core specimens, with less pain, in less time than with standard manual devices

Bone marrow sampling remains essential in the evaluation of hematopoietic and many non-hematopoietic disorders. One common limitation to these procedures is the discomfort experienced by patients. To address whether a Powered biopsy system could reduce discomfort while providing equivalent or better results, we performed a randomized trial in adult volunteers. Twenty-six subjects underwent bilateral biopsies with each device. Core samples were obtained in 66.7% of Manual insertions; 100% of Powered insertions (P=0.002). Initial mean biopsy core lengths were 11.1±4.5 mm for the Manual device; 17.0±6.8 mm for the Powered device (P<0.005). Pathology assessment for the Manual device showed a mean length of 6.1±5.6 mm, width of 1.0±0.7 mm, and volume of 11.0±10.8 mm3. Powered device measurements were mean length of 15.3±6.1 mm, width of 2.0±0.3 mm, and volume of 49.1±21.5 mm3 (P<0.001). The mean time to core ejection was 86 seconds for Manual device; 47 seconds for the Powered device (P<0.001). The mean second look overall pain score was 33.3 for the Manual device; 20.9 for the Powered (P=0.039). We conclude that the Powered biopsy device produces superior sized specimens, with less overall pain, in less time

Effects of organic carbon supply rates on mobility of previously bioreduced uranium in a contaminated sediment

Bioreduction-based strategies for remediating uranium (U)-contaminated sediments face the challenge of maintaining the reduced status of U for long times. Because groundwater influxes continuously bring in oxidizing terminal electron acceptors (O{sub 2}, NO{sub 3}{sup -}), it is necessary to continue supplying organic carbon (OC) to maintain the reducing environment after U bioreduction is achieved. We tested the influence of OC supply rates on mobility of previously microbial reduced uranium U(IV) in contaminated sediments. We found that high degrees of U mobilization occurred when OC supply rates were high, and when the sediment still contained abundant Fe(III). Although 900 days with low levels of OC supply minimized U mobilization, the sediment redox potential increased with time as did extractable U(VI) fractions. Molecular analyses of total microbial activity demonstrated a positive correlation with OC supply and analyses of Geobacteraceae activity (RT-qPCR of 16S rRNA) indicated continued activity even when the effluent Fe(II) became undetectable. These data support our earlier hypothesis on the mechanism responsible for re-oxidation of microbial reduced U(IV) under reducing conditions; that microbial respiration caused increased (bi)carbonate concentrations and formation of stable uranyl carbonate complexes, thereby shifted U(IV)/U(VI) equilibrium to more reducing potentials. The data also suggested that low OC concentrations could not sustain the reducing condition of the sediment for much longer time

Some Cubic Couplings in Type IIB Supergravity on AdS5×S5AdS_5\times S^5 and Three-point Functions in SYM_4 at Large N

All cubic couplings in type IIB supergravity on $AdS_5\times S^5$ that involve two scalar fields $s^I$ that are mixtures of the five form field strength on $S^5$ and the trace of the graviton on $S^5$ are derived by using the covariant equations of motion and the quadratic action for type IIB supergravity on $AdS_5\times S^5$. All corresponding three-point functions in SYM$_4$ are calculated in the supergravity approximation. It is pointed out that the scalars $s^I$ correspond not to the chiral primary operators in the ${\cal N}=4$ SYM but rather to a proper extension of the operators.Comment: Latex, 24p, misprints are correcte

Influences of organic carbon supply rate on uranium bioreduction in initially oxidizing, contaminated sediment

Remediation of uranium (U) contaminated sediments through in-situ stimulation of bioreduction to insoluble UO{sub 2} is a potential treatment strategy under active investigation. Previously, we found that newly reduced U(IV) can be reoxidized under reducing conditions sustained by a continuous supply of organic carbon (OC) because of residual reactive Fe(III) and enhanced U(VI) solubility through complexation with carbonate generated through OC oxidation. That finding motivated this investigation directed at identifying a range of OC supply rates that is optimal for establishing U bioreduction and immobilization in initially oxidizing sediments. The effects of OC supply rate, from 0 to 580 mmol OC (kg sediment){sup -1} year{sup -1}, and OC form (lactate and acetate) on U bioreduction were tested in flow-through columns containing U-contaminated sediments. An intermediate supply rate on the order of 150 mmol OC (kg sediment){sup -1} year{sup -1} was determined to be most effective at immobilizing U. At lower OC supply rates, U bioreduction was not achieved, and U(VI) solubility was enhanced by complexation with carbonate (from OC oxidation). At the highest OC supply rate, resulting highly carbonate-enriched solutions also supported elevated levels of U(VI), even though strongly reducing conditions were established. Lactate and acetate were found to have very similar geochemical impacts on effluent U concentrations (and other measured chemical species), when compared at equivalent OC supply rates. While the catalysts of U(VI) reduction to U(IV) are presumably bacteria, the composition of the bacterial community, the Fe reducing community, and the sulfate reducing community had no direct relationship with effluent U concentrations. The OC supply rate has competing effects of driving reduction of U(VI) to low solubility U(IV) solids, as well as causing formation of highly soluble U(VI)-carbonato complexes. These offsetting influences will require careful control of OC supply rates in order to optimize bioreduction-based U stabilization

Ophthalmic Artery Chemosurgery for Less Advanced Intraocular Retinoblastoma: Five Year Review

BACKGROUND: Ophthalmic artery chemosurgery (OAC) for retinoblastoma was introduced by us 5 years ago for advanced intraocular retinoblastoma. Because the success was higher than with existing alternatives and systemic side effects limited we have now treated less advanced intraocular retinoblastoma (Reese-Ellsworth (RE) I-III and International Classification Retinoblastoma (ICRB) B and C). METHODOLOGY/PRINCIPAL FINDINGS: Retrospective review of 5 year experience in eyes with Reese Ellsworth (Table 1) I (7 eyes), II (6 eyes) or III (6 eyes) and/or International Classification (Table 2) B (19 eyes) and C (11 eyes) treated with OAC (melphalan with or without topotecan) introduced directly into the ophthalmic artery. Patient survival was 100%. Ocular event-free survival was 100% for Reese-Ellsworth Groups I, II and III (and 96% for ICRB B and C) at a median of 16 months follow-up. One ICRB Group C (Reese-Ellsworth Vb) eye could not be treated on the second attempt for technical reasons and was therefore enucleated. No patient required a port and only one patient required transfusion of blood products. The electroretinogram (ERG) was unchanged or improved in 14/19 eyes. CONCLUSIONS/SIGNIFICANCE: Ophthalmic artery chemosurgery for retinoblastoma that was Reese-Ellsworth I, II and III (or International Classification B or C) was associated with high success (100% of treatable eyes were retained) and limited toxicity with results that equal or exceed conventional therapy with less toxicity

Vortices, Instantons and Branes

The purpose of this paper is to describe a relationship between the moduli space of vortices and the moduli space of instantons. We study charge k vortices in U(N) Yang-Mills-Higgs theories and show that the moduli space is isomorphic to a special Lagrangian submanifold of the moduli space of k instantons in non-commutative U(N) Yang-Mills theories. This submanifold is the fixed point set of a U(1) action on the instanton moduli space which rotates the instantons in a plane. To derive this relationship, we present a D-brane construction in which the dynamics of vortices is described by the Higgs branch of a U(k) gauge theory with 4 supercharges which is a truncation of the familiar ADHM gauge theory. We further describe a moduli space construction for semi-local vortices, lumps in the CP(N) and Grassmannian sigma-models, and vortices on the non-commutative plane. We argue that this relationship between vortices and instantons underlies many of the quantitative similarities shared by quantum field theories in two and four dimensions.Comment: 32 Pages, 4 Figure

Longitudinal peak strain detects a smaller risk area than visual assessment of wall motion in acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Opening of an occluded infarct related artery reduces infarct size and improves survival in acute ST-elevation myocardial infarction (STEMI). In this study we performed tissue Doppler analysis (peak strain, displacement, mitral annular movement (MAM)) and compared with visual assessment for the study of the correlation of measurements of global, regional and segmental function with final infarct size and transmurality. In addition, myocardial risk area was determined and a prediction sought for the development of infarct transmurality ≥50%.</p> <p>Methods</p> <p>Twenty six patients with STEMI submitted for primary percutaneous coronary intervention (PCI) were examined with echocardiography on the catheterization table. Four to eight weeks later repeat echocardiography was performed for reassessment of function and magnetic resonance imaging for the determination of final infarct size and transmurality.</p> <p>Results</p> <p>On a global level, wall motion score index (WMSI), ejection fraction (EF), strain, and displacement all showed significant differences (p ≤ 0.001, p ≤ 0.001, p ≤ 0.001 and p = 0.03) between the two study visits, but MAM did not (p = 0.17). On all levels (global, regional and segmental) and both pre- and post PCI, WMSI showed a higher correlation with scar transmurality compared to strain. We found that both strain and WMSI predicted the development of scar transmurality ≥50%, but strain added no significant information to that obtained with WMSI in a logistic regression analysis.</p> <p>Conclusions</p> <p>In patients with acute STEMI, WMSI, EF, strain, and displacement showed significant changes between the pre- and post PCI exam. In a ROC-analysis, strain had 64% sensitivity at 80% specificity and WMSI around 90% sensitivity at 80% specificity for the detection of scar with transmurality ≥50% at follow-up.</p

BEASTS OF THE SOUTHERN WILD: DISCOVERY OF NINE ULTRA FAINT SATELLITES IN THE VICINITY OF THE MAGELLANIC CLOUDS

We have used the publicly released Dark Energy Survey data to hunt for new satellites of the Milky Way in the Southern hemisphere. Our search yielded a large number of promising candidates. In this paper, we announce the discovery of 9 new unambiguous ultra-faint objects, whose authenticity can be established with the DES data alone. Based on the morphological properties, three of the new satellites are dwarf galaxies, one of which is located at the very outskirts of the Milky Way, at a distance of 380 kpc. The remaining 6 objects have sizes and luminosities comparable to the Segue~1 satellite and can not be classified straightforwardly without follow-up spectroscopic observations. The satellites we have discovered cluster around the LMC and the SMC. We show that such spatial distribution is unlikely under the assumption of isotropy, and, therefore, conclude that at least some of the new satellites must have been associated with the Magellanic Clouds in the past.Comment: Accepted to ApJ; See also 1503.02584; Changes w.r.t. v2: the discussion section updated slightly; small changes in the table with satellite parameter