HIGHLY EFFECTIVE LUNG DELIVERY OF A FULLY HUMAN MONOCLONAL ANTIBODY TARGETING PSEUDOMONAS AERUGINOSA FOLLOWING INTRA-NASAL ADMINISTRATION

A time-course study was performed to assess lung concentrations and bioactivities of a fully human monoclonal antibody (mAb) targeting Pseudomonas aeruginosa (PA) flagella type b (LST-007) following intra-nasal administration. Intra-nasal administration of LST-007 (5 mg/kg) resulted in high mAb concentrations (11 µg/ml) within the bronchoalveolar lavage (BAL) fluid at 15 min post-administration, which decreased to 3 µg/ml at 4 hr. In marked contrast, LST-007 concentrations in blood were 110 and 11 fold lower at the same time points. Scrutinization of BAL fluid demonstrated the presence of both intact and immunoreactive LST-007 towards PAO1 bacteria, which impeded bacterial motility, underscoring the maintenance of biological activity. These compelling data lay credence that intra-nasal and thus potential inhalation modes of administration might represent bona fide routes for a targeted mAb delivery to the lung environment and establishment of therapeutically effective concentrations. Such delivery approaches could help combat life-threatening, pneumonia infections caused by PA. KEY WORDS:Monoclonal antibody, intra-nasal, bronchoalveolar lavage; Pseudomonas aeruginos

Light emission enhancement using randomly distributed plasmonic nanoparticle arrays

We have fabricated and characterised the optical properties of solution processed randomly distributed gold nanoparticle plasmonic arrays that are coated with a thin-film fluorescent dye. Three times enhancement in the emission intensity of the fluorescent dye Pyridine 2 has been observed. Our results are further supported by finite difference time domain simulations that predicted up to 7 times enhancements in the emission intensity as a result of the coupling between the molecular dipoles and the confined field in the underlying plasmonic array. Our results demonstrate the potential of using such structures in organic light emitting devices and chemical and bio-sensing applications

Efficient out-coupling and beaming of Tamm optical states via surface plasmon polariton excitation

We present evidence of optical Tamm states to surface plasmon polariton (SPP) coupling. We experimentally demonstrate that for a Bragg stack with a thin metal layer on the surface, hybrid Tamm-SPP modes may be excited when a grating on the air-metal interface is introduced. Out-coupling via the grating to free space propagation is shown to enhance the transmission as well as the directionality and polarization selection for the transmitted beam. We suggest that this system will be useful on those devices, where a metallic electrical contact as well as beaming and polarization control is needed

1/4 Partial Breaking of Global Supersymmetry and New Superparticle Actions

We construct the worldline superfield massive superparticle actions which preserve 1/4 portion of the underlying higher-dimensional supersymmetry. The rest of supersymmetry is spontaneously broken and realized by nonlinear transformations. We consider the cases of N=4 to N=1 and N=8 to N=2 partial breaking. In the first case we present the corresponding Green-Schwarz type target superspace action with one $\kappa$-supersymmetry. It is related to the superfield action via a field redefinition. In the second case we find out two possible models, one of which is a direct generalization of the N=4 to N=1 case, while another is essentially different. For the first model we formulate Green-Schwarz type action with two kappa supersymmetries. We elaborate on the bosonic part of the superfield action for the second model and find that only in two special limits it takes the standard Nambu-Goto form. In the general case it is determined by a fourth-order algebraic equation. The characteristic common feature of these new superparticle models is that the algebras of their spontaneously broken supersymmetries are non-trivial truncations of the general extensions of N=1 and N=2 Poincare D=4 superalgebras by tensorial central charges.Comment: 22 page

Persistent near-infrared photoconductivity of ZnO nanoparticles based on plasmonic hot charge carriers

We report on the coupling of ZnO nanoparticles with plasmonic gold nanoislands in a solution processed photodetector, which results in a clear enhancement in the optical absorption and the electrical responsivity of ZnO nanoparticles to cover the visible and the near-IR (NIR) spectral range, well beyond its intrinsic optical absorption. This enhancement, which arises from the coupling between ZnO nanoparticles and the plasmonically mediated hot electron generation in the Au plasmonic nanoislands, results in a significant plasmonically driven photoresponse in the NIR of 2.5×10-5 A/W. The recorded photocurrent exhibits a persistent behaviour, which is attributed to surface defect states in the ZnO nanoparticles. This study provides a route to solution processed, low-cost device fabrication schemes with important implications on low processing temperature optoelectronics technology to enhance the performance of photovoltaic devices over a wide solar spectrum. Additionally, this unusual behaviour paves the way towards harnessing plasmonic resonances to probe and examine the surface defects of metal oxide semiconductors

Readability of Wikipedia Pages on Autoimmune Disorders: Systematic Quantitative Assessment

Background: In the era of new information and communication technologies, the Internet is being increasingly accessed for health-related information. Indeed, recently published patient surveys of people with autoimmune disorders confirmed that the Internet was reported as one of the most important health information sources. Wikipedia, a free online encyclopedia launched in 2001, is generally one of the most visited websites worldwide and is often consulted for health-related information. Objective: The main objective of this investigation was to quantitatively assess whether the Wikipedia pages related to autoimmune disorders can be easily accessed by patients and their families, in terms of readability. Methods: We obtained and downloaded a list of autoimmune disorders from the American Autoimmune Related Diseases Association (AARDA) website. We analyzed Wikipedia articles for their overall level of readability with 6 different quantitative readability scales: (1) the Flesch Reading Ease, (2) the Gunning Fog Index, (3) the Coleman-Liau Index, (4) the Flesch-Kincaid Grade Level, (5) the Automated Readability Index (ARI), and (6) the Simple Measure of Gobbledygook (SMOG). Further, we investigated the correlation between readability and clinical, pathological, and epidemiological parameters. Moreover, each Wikipedia analysis was assessed according to its content, breaking down the readability indices by main topic of each part (namely, pathogenesis, treatment, diagnosis, and prognosis plus a section containing paragraphs not falling into any of the previous categories). Results: We retrieved 134 diseases from the AARDA website. The Flesch Reading Ease yielded a mean score of 24.34 (SD 10.73), indicating that the sites were very difficult to read and best understood by university graduates, while mean Gunning Fog Index and ARI scores were 16.87 (SD 2.03) and 14.06 (SD 2.12), respectively. The Coleman-Liau Index and the Flesch-Kincaid Grade Level yielded mean scores of 14.48 (SD 1.57) and 14.86 (1.95), respectively, while the mean SMOG score was 15.38 (SD 1.37). All the readability indices confirmed that the sites were suitable for a university graduate reading level. We found no correlation between readability and clinical, pathological, and epidemiological parameters. Differences among the different sections of the Wikipedia pages were statistically significant. Conclusions: Wikipedia pages related to autoimmune disorders are characterized by a low level of readability. The onus is, therefore, on physicians and health authorities to improve the health literacy skills of patients and their families and to create, together with patients themselves, disease-specific readable sites, disseminating highly accessible health-related online information, in terms of both clarity and conciseness

D-branes in Generalized Geometry and Dirac-Born-Infeld Action

The purpose of this paper is to formulate the Dirac-Born-Infeld (DBI) action in a framework of generalized geometry and clarify its symmetry. A D-brane is defined as a Dirac structure where scalar fields and gauge field are treated on an equal footing in a static gauge. We derive generalized Lie derivatives corresponding to the diffeomorphism and B-field gauge transformations and show that the DBI action is invariant under non-linearly realized symmetries for all types of diffeomorphisms and B-field gauge transformations. Consequently, we can interpret not only the scalar field but also the gauge field on the D-brane as the generalized Nambu-Goldstone boson.Comment: 32 pages, 4 figures, ver2:typos corrected, references adde

Use of Secukinumab in a Cohort of Erythrodermic Psoriatic Patients: A Pilot Study

Erythrodermic psoriasis (EP) is a dermatological emergency and its treatment with secukinumab is still controversial. Furthermore, no data exist regarding the prognostic value of drug abuse in such a condition. We performed a multi-center, international, retrospective study, enrolling a sample of EP patients (body surface area > 90%) who were treated with secukinumab (300 mg) during the study period from December 2015 to December 2018. Demographics and clinical data were collected. Drug abuses were screened and, specifically, smoking status (packages/year), cannabis use (application/week) and alcoholism-tested with the Alcohol Use Disorders Identification Test (AUDIT)-were assessed. All patients were followed for up to 52 weeks. We enrolled 13 EP patients, nine males, and four females, with a median age of 40 (28-52) years. Patients na\uefve to biologic therapy were 3/13. Regarding drug use, seven patients had a medium-high risk of alcohol addiction, three used cannabis weekly, and seven were smokers with a pack/year index of 295 (190-365). The response rate to secukinumab was 10/13 patients with a median time to clearance of three weeks (1.5-3). No recurrences were registered in the 52-week follow-up and a Psoriasis Area Severity Index (PASI) score of 90 was achieved. The entire cohort of non-responders (n = 3) consumed at least two drugs of abuse (alcohol, smoking or cannabis). Non-responders were switched to ustekinumab and obtained a PASI 100 in 24 weeks. However, given our observed number of patients using various drugs in combination with secukinumab in EP, further studies are needed to ascertain drug abuse prevalence in a larger EP cohort. Secukinumab remains a valid, effective and safe therapeutic option for EP

The Pioneer anomaly in the context of the braneworld scenario

We examine the Pioneer anomaly - a reported anomalous acceleration affecting the Pioneer 10/11, Galileo and Ulysses spacecrafts - in the context of a braneworld scenario. We show that effects due to the radion field cannot account for the anomaly, but that a scalar field with an appropriate potential is able to explain the phenomena. Implications and features of our solution are analyzed.Comment: Final version to appear at Classical & Quantum Gravity. Plainlatex 19 page