Engineered arrays of NV color centers in diamond based on implantation of CN- molecules through nanoapertures

We report a versatile method to engineer arrays of nitrogen-vacancy (NV) color centers in dia- mond at the nanoscale. The defects were produced in parallel by ion implantation through 80 nm diameter apertures patterned using electron beam lithography in a PMMA layer deposited on a diamond surface. The implantation was performed with CN- molecules which increased the NV defect formation yield. This method could enable the realization of a solid-state coupled-spin array and could be used for positioning an optically active NV center on a photonic microstructure.Comment: 12 pages, 3 figure

Leading change in academic pharmacy: Report of the 2018-2019 aacp academic affairs committee

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Delivering an effective drug load to the posterior section of the ocular tissues, while using a non-invasive technique, has always been a challenge. In this regard, the goal of the present study was to develop sustained release triamcinolone acetonide (TA) loaded polymeric matrix films for ocular delivery. The TA-films were prepared in two different polymer matrices, with drug loadings of 10% and 20% w/w, and they were evaluated for ocular distribution in vivo in a conscious rabbit model. A 4% w/v TA suspension (TA-C) was used as a control for in vitro and in vivo studies. The TA-films, prepared with melt-cast technology, used polyethylene oxide (PEO) and Soluplus® as the polymer matrix. The films were evaluated with respect to assay, content uniformity, excipient interaction, and permeability across isolated rabbit sclera. The distribution of TA in the ocular tissues, post topical administration, was determined in New Zealand male albino rabbits as a function of dose, and was compared against TA-C. The assay of the 10% and 20% w/w film was in the range from 70–79% and 92–94% for the Soluplus® and PEO films, respectively, and content uniformity was in the range of 95–103% for both the films. The assay of the TA from Soluplus® films was less compared with the PEO films and showed an interaction with TA, as revealed by Differential Scanning Calorimetry (DSC). Hence, Soluplus® films were not selected for further studies. No interaction was observed between the drug and PEO polymer matrix. The enhancement of trans-scleral flux and permeability of TA was about 1.16 and 1.33-folds, respectively, from the 10% w/w PEO and 3.5 and 2.12-folds, respectively, from the 20% w/w PEO films, as compared with TA-C formulations. The in vivo studies demonstrate that significantly higher TA levels were observed in the anterior and posterior segments of the eye at the end of 6h with the PEO films. Therefore, the PEO based polymeric films were able to deliver TA into the back of the eye efficiently and for prolonged periods. View Full-Tex

Vascular perfusion and hypoxic areas in RIF-1 tumours after photodynamic therapy.

The influence of photodynamic therapy (PDT) on vascular perfusion and the development of hypoxia was investigated in the murine RIF-1 tumour. Image analysis was used to quantify changes in perfusion and hypoxia at 5 min after interstitial Photofrin-mediated PDT. The fluorescent stain Hoechst 33342 was used as an in vivo marker of functional vascular perfusion and the antibody anti-collagen type IV as a marker of the tumour vasculature. The percentage of total tumour vasculature that was perfused decreased to less than 30% of control values after PDT. For the lower light doses this decrease was more pronounced in the centre of the tumour. The observed reduction in vascular perfusion showed a good linear correlation (r = 0.98) with previously published tumour perfusion data obtained with the 86Rb extraction technique. The image analysis technique provides extra information concerning the localisation of (non)-perfused vessels. To detect hypoxic tumour areas in vivo, an immunohistochemical method was used employing NITP [7-(4'-(2-nitroimidazol-1-yl)-butyl)-theophylline]. A large increase in hypoxic areas was found for PDT-treated tumours. More than half the total tumour area was hypoxic after PDT, compared with < 4% for control tumours. Our studies illustrate the potential of image analysis systems for monitoring the functional consequences of PDT-mediated vascular damage early after treatment. This provides direct confirmation that the perfusion changes lead to tissue hypoxia, which has implications for the combined treatment of PDT with bioreductive drugs

Spin dynamics in the optical cycle of single nitrogen-vacancy centres in diamond

We investigate spin-dependent decay and intersystem crossing in the optical cycle of single negatively-charged nitrogen-vacancy (NV) centres in diamond. We use spin control and pulsed optical excitation to extract both the spin-resolved lifetimes of the excited states and the degree of optically-induced spin polarization. By optically exciting the centre with a series of picosecond pulses, we determine the spin-flip probabilities per optical cycle, as well as the spin-dependent probability for intersystem crossing. This information, together with the indepedently measured decay rate of singlet population provides a full description of spin dynamics in the optical cycle of NV centres. The temperature dependence of the singlet population decay rate provides information on the number of singlet states involved in the optical cycle.Comment: 11 pages, 5 figure

Disentangling the effects of environmental conditions on wintering and breeding grounds on age-specific survival rates in a trans-Saharan migratory raptor

International audienceMigratory species are subject to environmental variability occurring on breeding and wintering grounds. Estimating the relative contribution of environmental factors experienced sequentially during breeding and wintering, and their potential interaction, to the variation of survival is crucial to predict population viability of migratory species. Here we investigated this issue for the Montagu's harrier Circus pygargus, a trans‐Saharan migrant. We analysed capture‐recapture data from a 29‐yr long monitoring of wing‐tagged offspring and adults at two study sites in France (Rochefort‐RO & Maine‐et‐Loire‐ML). The study period covers a climatic shift occurring in the Sahel with increasing rainfall following a period of droughts (Sahel greening). We found that harriers’ adult survival in RO (between 1988 and 2005) varied over time and was sensitive to the interaction between the amount of rainfall in the Sahel and the annual mean breeding success, two proxies of prey availability. The occurrence of adverse conditions on breeding and wintering grounds in the same year decreased survival from 0.70‐0.77 to 0.48 ± 0.05. Juvenile survival in RO was slightly more sensitive to conditions in Europe than in the Sahel. Unexpectedly, lower survival rates were found in years with higher mean breeding success, suggesting compensatory density feedbacks may operate. By contrast, adult survival in ML, monitored between 1999 and 2017, was higher compared to RO (0.76 ± 0.03 vs. 0.66 ± 0.02), remained constant and unaffected by any proxy of prey availability. This difference seems consistent with the fact that harriers in ML experienced better and especially less variable environmental conditions during breeding and wintering seasons compared to RO. Overall, we showed that survival of a migratory bird is sensitive to the level of variability in environmental conditions and that adverse conditions on wintering grounds can amplify the negative effects of conditions during the previous breeding season on birds’ survival

Fellowships in Community Pharmacy Research: Experiences of Five Schools and Colleges of Pharmacy

Objective To describe common facilitators, challenges, and lessons learned in 5 schools and colleges of pharmacy in establishing community pharmacy research fellowships. Setting: Five schools and colleges of pharmacy in the United States. Practice description: Schools and colleges of pharmacy with existing community partnerships identified a need and ability to develop opportunities for pharmacists to engage in advanced research training. Practice innovation: Community pharmacy fellowships, each structured as 2 years long and in combination with graduate coursework, have been established at the University of Pittsburgh, Purdue University, East Tennessee State University, University of North Carolina at Chapel Hill, and The Ohio State University. Evaluation: Program directors from each of the 5 community pharmacy research fellowships identified common themes pertaining to program structure, outcomes, and lessons learned to assist others planning similar programs. Results: Common characteristics across the programs include length of training, prerequisites, graduate coursework, mentoring structure, and immersion into a pharmacist patient care practice. Common facilitators have been the existence of strong community pharmacy partnerships, creating a fellowship advisory team, and networking. A common challenge has been recruitment, with many programs experiencing at least one year without filling the fellowship position. All program graduates (n = 4) have been successful in securing pharmacy faculty positions. Conclusion: Five schools and colleges of pharmacy share similar experiences in implementing community pharmacy research fellowships. Early outcomes show promise for this training pathway in growing future pharmacist-scientists focused on community pharmacy practice

Validation of the German version of the Family Reported Outcome Measure (FROM-16) to assess the impact of disease on the partner or family member

Background The Family Reported Outcome Measure (FROM-16) assesses the impact of a patient’s chronic illness on the quality of life (QoL) of the patient’s partner or family members. The aim of the study was to translate, explore the structure of and validate the FROM-16. Methods The questionnaire was translated from English into German (forward, backward, four independent translators). Six interviews with family members were conducted to confirm the questionnaire for linguistic, conceptual, semantic and experiential equivalence and its practicability. The final German translation was tested for internal consistency, reproducibility and test validity. Criterion validity was tested by correlating the scores of the FROM-16 and the Global Health Scale (GHS). Principal component analysis, factor analysis, and confirmatory factor analysis was used to assess the questionnaire’s structure and its domains. Reliability and reproducibility were tested computing the intraclass correlation coefficient (ICC) using one sample t-test for testing the hypothesis that the difference between the scores was not different from zero. Results Overall, 83 family members (61% female, median age: 61 years) completed the questionnaire at two different times (mean interval: 22 days). Internal consistency was good for the FROM-16 scores (Cronbach’s α for total score = 0.86). In those with stable GHS, the ICC for the total score was 0.87 and the difference was not different from zero (p = 0.262) indicating reproducible results. A bi-factor model with a general factor including all items, and two sub-factors comprising the items from the original 2-factor construct had the best fit. Conclusions The German FROM-16 has good reliability, test validity and practicability. It can be considered as an appropriate and generic tool to measure QoL of a patient’s partner or family member. Due to the presence of several cross-loadings we do not recommend the reporting of the scores of the two domains proposed for the original version of FROM-16 when using the German version. Thus, in reporting the results emphasis should be put on the total score

Distinct Mechanisms for Induction and Tolerance Regulate the Immediate Early Genes Encoding Interleukin 1β and Tumor Necrosis Factor α

Interleukin-1β and Tumor Necrosis Factor α play related, but distinct, roles in immunity and disease. Our study revealed major mechanistic distinctions in the Toll-like receptor (TLR) signaling-dependent induction for the rapidly expressed genes (IL1B and TNF) coding for these two cytokines. Prior to induction, TNF exhibited pre-bound TATA Binding Protein (TBP) and paused RNA Polymerase II (Pol II), hallmarks of poised immediate-early (IE) genes. In contrast, unstimulated IL1B displayed very low levels of both TBP and paused Pol II, requiring the lineage-specific Spi-1/PU.1 (Spi1) transcription factor as an anchor for induction-dependent interaction with two TLR-activated transcription factors, C/EBPβ and NF-κB. Activation and DNA binding of these two pre-expressed factors resulted in de novo recruitment of TBP and Pol II to IL1B in concert with a permissive state for elongation mediated by the recruitment of elongation factor P-TEFb. This Spi1-dependent mechanism for IL1B transcription, which is unique for a rapidly-induced/poised IE gene, was more dependent upon P-TEFb than was the case for the TNF gene. Furthermore, the dependence on phosphoinositide 3-kinase for P-TEFb recruitment to IL1B paralleled a greater sensitivity to the metabolic state of the cell and a lower sensitivity to the phenomenon of endotoxin tolerance than was evident for TNF. Such differences in induction mechanisms argue against the prevailing paradigm that all IE genes possess paused Pol II and may further delineate the specific roles played by each of these rapidly expressed immune modulators. © 2013 Adamik et al