CD44 aptamer mediated cargo delivery to lysosomes of retinal pigment epithelial cells to prevent age-related macular degeneration

Age related macular degeneration (AMD) is a progressive, neurodegenerative disorder that leads to the severe loss of central vision in elderlies. The health of retinal pigment epithelial (RPE) cells is critical for the onset of AMD. Chronic oxidative stress along with loss of lysosomal activity is a major cause for RPE cell death during AMD. Hence, development of a molecule for targeted lysosomal delivery of therapeutic protein/drugs in RPE cells is important to prevent RPE cell death during AMD. Using human RPE cell line (ARPE-19 cells) as a study model, we confirmed that hydrogen peroxide (H2O2) induced oxidative stress results in CD44 cell surface receptor overexpression in RPE cells; hence, an important target for specific delivery to RPE cells during oxidative stress. We also demonstrate that the known nucleic acid CD44 aptamer - conjugated with a fluorescent probe (FITC) - is delivered into the lysosomes of CD44 expressing ARPE-19 cells. Hence, as a proof of concept, we demonstrate that CD44 aptamer may be used for lysosomal delivery of cargo to RPE cells under oxidative stress, similar to AMD condition. Since oxidative stress may induce wet and dry AMD, both, along with proliferative vitreoretinopathy, CD44 aptamer may be applicable as a carrier for targeted lysosomal delivery of therapeutic cargoes in ocular diseases showing oxidative stress in RPE cells. © 2019Peer reviewe

Discovery of a red quasar with recurrent activity

We report a new double-double radio quasar, DDRQ, J0746$+$4526 which exhibits two cycles of episodic activity. From radio continuum observations at 607 MHz using the GMRT and 1400 MHz from the FIRST survey we confirm its episodic nature. We examine the SDSS optical spectrum and estimate the black hole mass to be (8.2$\pm$0.3)$\times$10$^7$M$_\odot$ from its observed MgII emission line, and the Eddington ratio to be 0.03. The black hole mass is significantly smaller than for the other reported DDRQ, J0935+0204, while the Eddington ratios are comparable. The SDSS spectrum is significantly red continuum dominated suggesting that it is highly obscured with ${E(B-V)}_{host}=0.70\pm0.16$ mag. This high obscuration further indicates the existence of a large quantity of dust and gas along the line of sight, which may have a key role in triggering the recurrent jet activity in such objects.Comment: 5 pages, 3 figures, 1 table. Accepted for publication in Ap

Bessel-Maitland Function of Several Variables and its Properties Related to Integral Transforms and Fractional Calculus

In the recent years, various generalizations of Bessel function were introduced and its various properties were investigated by many authors. Bessel-Maitland function is one of the generalizations of Bessel function. The objective of this paper is to establish a new generalization of Bessel-Maitland function using the extension of beta function involving Appell series and Lauricella functions. Some of its properties including recurrence relation, integral representation and differentiation formula are investigated. Moreover, some properties of Riemann-Liouville fractional operator associated with the new generalization of Bessel-Maitland function are also discussed

MintHint: Automated Synthesis of Repair Hints

Being able to automatically repair programs is an extremely challenging task. In this paper, we present MintHint, a novel technique for program repair that is a departure from most of today's approaches. Instead of trying to fully automate program repair, which is often an unachievable goal, MintHint performs statistical correlation analysis to identify expressions that are likely to occur in the repaired code and generates, using pattern-matching based synthesis, repair hints from these expressions. Intuitively, these hints suggest how to rectify a faulty statement and help developers find a complete, actual repair. MintHint can address a variety of common faults, including incorrect, spurious, and missing expressions. We present a user study that shows that developers' productivity can improve manyfold with the use of repair hints generated by MintHint -- compared to having only traditional fault localization information. We also apply MintHint to several faults of a widely used Unix utility program to further assess the effectiveness of the approach. Our results show that MintHint performs well even in situations where (1) the repair space searched does not contain the exact repair, and (2) the operational specification obtained from the test cases for repair is incomplete or even imprecise

A low-frequency study of recently identified double-double radio galaxies

In order to understand the possible mechanisms of recurrent jet activity in radio galaxies and quasars, which are still unclear, we have identified such sources with a large range of linear sizes (220 $-$ 917 kpc), and hence time scales of episodic activity. Here we present high-sensitivity 607-MHz Giant Metrewave Radio Telescope (GMRT) images of 21 possible double-double radio galaxies (DDRGs) identified from the FIRST survey to confirm their episodic nature. These GMRT observations show that none of the inner compact components suspected to be hot-spots of the inner doubles are cores having a flat radio spectrum, confirming the episodic nature of these radio sources. We have indentified a new DDRG with a candidate quasar, and have estimated the upper spectral age limits for eight sources which showed marginal evidence of steepening at higher frequencies. The estimated age limits (11 $-$ 52 Myr) are smaller than those of the large-sized ($\sim$ 1 Mpc) DDRGs.Comment: Accepted for publication in MNRAS. 14 pages, 7 figure

The effect of housing on the mental health of older people: the impact of lifetime housing history in Whitehall II

Background: This study describes differences in trajectories of self-reported mental health in an ageing cohort, according to their housing, while controlling for confounders.Methods: The General Health Questionnaire was measured on six occasions as part of Whitehall II cohort study of office-based British civil servants (1985-2009); 10,308 men and women aged 35-55 at baseline.Results: Home-ownership was the predominant tenure at baseline and increased over the life-course, but the social gradient remained. In the bivariate analysis, by phase nine, renters had higher (poorer mental health) GHQ scores (55.48) than owner occupiers (51.98). Those who reported difficulty paying bills or problems with housing had higher GHQ scores at baseline (financial difficulties 57.70 vs 54.34; house problems 58.06 vs 53.99) and this relative difference increased by phase nine (financial difficulties 59.64 vs 51.67; house problems 56.68 vs 51.22). In multivariate models, the relative differences in GHQ scores by tenure increased with age, but were no longer significant after adjusting for confounders. Whereas GHQ scores for those with housing problems and financial difficulties were still significantly higher as participants grew older.Conclusion: The social gradient in the effect of home ownership on mental health, which is evident at baseline, diminishes as people get older, whereas housing quality and financial problems become relatively more important in explaining older people's health. Inequalities in housing quality and ability to deal with household financial problems will become increasingly important mental health issues as the population ages

Clinical evaluation of Nirgundi Taila and Dashmoola Ghrita in the management of Sandhigata Vata (Osteoarthritis)

Though Sandhigata Vata is described under the broad heading of Vatavyadhi in most of the Samhita and Sangraha Granthas, it is not included under 80 types of “Nanatmaja Vatavyadhi”, Charaka was first, who described separately Sandhigata Vata as - “Sandhigata Anila” in Vatavyadhi chapter. The clinical presentation of Sandhigata Vata resembles to Osteoarthritis, which is the most common form of arthritis. It begins asymptomatically in middle age with progressive symptoms in advancing age. It increases in prevalence with age especially in weight bearing joints. Female are prone with 25% prevalence were 16% in male. In present study 21 patients fulfilling diagnostic criteria of Sandhigata Vata were selected. Patients were treated with Nirgundi Taila locally 8ml on affected joints, with Dashmoola Ghrita 12g. with meal internally twice a day with luke warm water. After a course of therapy of 2 month symptomatic improvement was observed at various levels with better results in the patients treated with Nirgundi Taila and Dashmoola Ghrita

Deep optical survey of the stellar content of Sh2-311 region

The stellar content in and around Sh2-311 region have been studied using the deep optical observations as well as near-infrared (NIR) data from 2MASS. The region contains three clusters, viz. NGC 2467, Haffner 18 and Haffner 19. We have made an attempt to distinguish the stellar content of these individual regions as well as to re-determine their fundamental parameters such as distance, reddening, age, onto the basis of a new and more extended optical and infrared photometric data set. NGC 2467 and Haffner 19 are found to be located in the Perseus arm at the distances of 5.0 $\pm$ 0.4 kpc and 5.7 $\pm$ 0.4 kpc, respectively, whereas Haffner 18 is located at the distance of 11.2 $\pm$ 1.0 kpc. The clusters NGC 2467 and Haffner 19 might have formed from the same molecular cloud, whereas the cluster Haffner 18 is located in the outer galactic arm, i.e. the Norma-Cygnus arm. We identify 8 class II young stellar objects (YSOs) using the NIR $(J - H)/(H - K)$ two colour diagram. We have estimated the age and mass of the YSOs identified in the present work and those by Snider et al. (2009) using the $V/(V - I)$ colour-magnitude diagram. The estimated ages and mass range of the majority of the YSOs are $\lesssim$1 Myr and $\sim$0.4 - 3.5 \msun, respectively, indicating that these sources could be T-Tauri stars or their siblings. Spatial distribution of the YSOs shows that some of the YSOs are distributed around the H II region Sh2-311, suggesting a triggered star formation at its periphery.Comment: 19 pages, 13 figures, 9 table; Accepted for publication in New Astronom