Posterior Segment Approach for Subretinal Transplantation or Injection in the Canine Model

A posterior segment approach for cell transplantation or injection into the subretinal space of the dog has been developed. Controlled penetration to the subretinal space was achieved using a 29-gauge injection cannula, either blunted or with a 30° sharpened bevel, and partially ensheathed with moveable plastic tubing. Depending on the injection volume used, the retina detached, and the fluid was reabsorbed within 1–3 weeks, although for smaller volumes the retina reattached within a matter of days. The optimal injection volume used was between 100 and 150 μl, or two injections of 55 μl each. By ophthalmoscopy following the surgery, it was possible to serially monitor the injection site and retinal bleb through fundus photography. Light microscopy demonstrates the distribution of stable, viable RPE cells in the subretinal space up to 6 months. The transplantation technique developed for the dog is atraumatic and free from any major surgical or clinical complications. It can be readily used to deliver cells or fluids to localized regions of the subretinal space

Analysis of chromosome positions in the interphase nucleus of Chinese hamster cells by laser-UV-microirradiation experiments

Unsynchronized cells of an essentially diploid strain of female Chinese hamster cells derived from lung tissue (CHL) were laser-UV-microirradiated (=257 nm) in the nucleus either at its central part or at its periphery. After 7–9 h postincubation with 0.5 mM caffeine, chromosome preparations were made in situ. Twenty-one and 29 metaphase spreads, respectively, with partial chromosome shattering (PCS) obtained after micro-irradiation at these two nuclear sites, were Q-banded and analyzed in detail. A positive correlation was observed between the frequency of damage of chromosomes and both their DNA content and length at metaphase. No significant difference was observed between the frequencies of damage obtained for individual chromosomes at either site of microirradiation. The frequency of joint damage of homologous chromosomes was low as compared to nonhomologous ones. Considerable variation was noted in different cells in the combinations of jointly shattered chromosomes. Evidence which justifies an interpretation of these data in terms of an interphase arrangement of chromosome territories is discussed. Our data strongly argue against somatic pairing as a regular event, and suggest a considerable variability of chromosome positions in different nuclei. However, present data do not exclude the possibility of certain non-random chromosomal arrangements in CHL-nuclei. The interphase chromosome distribution revealed by these experiments is compared with centromere-centromere, centromere-center and angle analyses of metaphase spreads and the relationship between interphase and metaphase arrangements of chromosomes is discussed

Exoplanet Diversity in the Era of Space-based Direct Imaging Missions

This whitepaper discusses the diversity of exoplanets that could be detected by future observations, so that comparative exoplanetology can be performed in the upcoming era of large space-based flagship missions. The primary focus will be on characterizing Earth-like worlds around Sun-like stars. However, we will also be able to characterize companion planets in the system simultaneously. This will not only provide a contextual picture with regards to our Solar system, but also presents a unique opportunity to observe size dependent planetary atmospheres at different orbital distances. We propose a preliminary scheme based on chemical behavior of gases and condensates in a planet's atmosphere that classifies them with respect to planetary radius and incident stellar flux.Comment: A white paper submitted to the National Academy of Sciences Exoplanet Science Strateg

fMRI evidence of ‘mirror’ responses to geometric shapes

Mirror neurons may be a genetic adaptation for social interaction [1]. Alternatively, the associative hypothesis [2], [3] proposes that the development of mirror neurons is driven by sensorimotor learning, and that, given suitable experience, mirror neurons will respond to any stimulus. This hypothesis was tested using fMRI adaptation to index populations of cells with mirror properties. After sensorimotor training, where geometric shapes were paired with hand actions, BOLD response was measured while human participants experienced runs of events in which shape observation alternated with action execution or observation. Adaptation from shapes to action execution, and critically, observation, occurred in ventral premotor cortex (PMv) and inferior parietal lobule (IPL). Adaptation from shapes to execution indicates that neuronal populations responding to the shapes had motor properties, while adaptation to observation demonstrates that these populations had mirror properties. These results indicate that sensorimotor training induced populations of cells with mirror properties in PMv and IPL to respond to the observation of arbitrary shapes. They suggest that the mirror system has not been shaped by evolution to respond in a mirror fashion to biological actions; instead, its development is mediated by stimulus-general processes of learning within a system adapted for visuomotor control

MINERvA neutrino detector response measured with test beam data

The MINERvA collaboration operated a scaled-down replica of the solid scintillator tracking and sampling calorimeter regions of the MINERvA detector in a hadron test beam at the Fermilab Test Beam Facility. This article reports measurements with samples of protons, pions, and electrons from 0.35 to 2.0 GeV/c momentum. The calorimetric response to protons, pions, and electrons are obtained from these data. A measurement of the parameter in Birks' law and an estimate of the tracking efficiency are extracted from the proton sample. Overall the data are well described by a Geant4-based Monte Carlo simulation of the detector and particle interactions with agreements better than 4%, though some features of the data are not precisely modeled. These measurements are used to tune the MINERvA detector simulation and evaluate systematic uncertainties in support of the MINERvA neutrino cross section measurement program.Comment: as accepted by NIM

First Measurement of Coherent Elastic Neutrino-Nucleus Scattering on Argon

We report the first measurement of coherent elastic neutrino-nucleus scattering (\cevns) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two independent analyses prefer \cevns over the background-only null hypothesis with greater than $3\sigma$ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2 $\pm$ 0.7) $\times$10$^{-39}$ cm$^2$ -- consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the \cevns process and provides improved constraints on non-standard neutrino interactions.Comment: 8 pages, 5 figures with 2 pages, 6 figures supplementary material V3: fixes to figs 3,4 V4: fix typo in table 1, V5: replaced missing appendix, V6: fix Eq 1, new fig 3, V7 final version, updated with final revision

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

PDMS microfluidics developed for polymer based photonic biosensors

In this work, advances in the fabrication technology and functional analysis of a polymer microfluidic system-as a significant part of a developed polymer photonic biosensor-are reported. Robust and cost-effective microfluidics in PDMS including sample preparation functions is designed and realized by using SU-8 moulding replica. Surface modification strategies using Triton X-100 and PDMS-PEO and their effect on device sealing and non-specific protein adsorption are investigated by contact angle measurement and in situ fluorescence microscopy. © 2014 Springer-Verlag Berlin Heidelberg

Indispensable Ocean: Aligning Ocean Health and Human Well-Being

The ocean is a critical part of Earth's life-support system and vital for the well-being of humanity. Once thought to be limitless, the ocean's resources are showing serious signs of deterioration and depletion on a global scale. Adverse changes are accelerating at an unprecedented rate relative to the changes seen over millions of years.This report is the result of a conversation by the Blue Ribbon Panel, a group of diverse leaders in industry, government, conservation, and academia who aim to serve as a collective voice to build sustainable solutions for the ocean

Mannose-binding lectin-deficient genotypes as a risk factor of pneumococcal meningitis in infants

OBJECTIVES: The objective of this study was to evaluate to evaluate the role of mannose-binding-lectin deficient genotypes in pneumococcal meningitis (PM) in children. METHODS: We performed a 16-year retrospective study (January 2001 to March 2016) including patients ≤ 18 years with PM. Variables including attack rate of pneumococcal serotype (high or low invasive capacity) and MBL2 genotypes associated with low serum MBL levels were recorded. RESULTS: Forty-eight patients were included in the study. Median age was 18.5 months and 17/48 episodes (35.4%) occurred in children ≤ 12 months old. Serotypes with high-invasive disease potential were identified in 15/48 episodes (31.2%). MBL2 deficient genotypes accounted for 18.8% (9/48). Children ≤ 12 months old had a 7-fold risk (95% CI: 1.6-29.9; p 12 months old. A sub-analysis of patients by age group revealed significant proportions of carriers of MBL2 deficient genotypes among those ≤ 12 months old with PM caused by opportunistic serotypes (54.5%), admitted to the PICU (Pediatric Intensive Care Unit) (46.7%) and of White ethnicity (35.7%). These proportions were significantly higher than in older children (all p<0.05). CONCLUSIONS: Our results suggest that differences in MBL2 genotype in children ≤12 months old affects susceptibility to PM, and it may have an important role in the episodes caused by non-high invasive disease potential serotypes