Noninfectious retrovirus particles drive the APOBEC3/Rfv3 dependent neutralizing antibody response.

Members of the APOBEC3 family of deoxycytidine deaminases counteract a broad range of retroviruses in vitro through an indirect mechanism that requires virion incorporation and inhibition of reverse transcription and/or hypermutation of minus strand transcripts in the next target cell. The selective advantage to the host of this indirect restriction mechanism remains unclear, but valuable insights may be gained by studying APOBEC3 function in vivo. Apobec3 was previously shown to encode Rfv3, a classical resistance gene that controls the recovery of mice from pathogenic Friend retrovirus (FV) infection by promoting a more potent neutralizing antibody (NAb) response. The underlying mechanism does not involve a direct effect of Apobec3 on B cell function. Here we show that while Apobec3 decreased titers of infectious virus during acute FV infection, plasma viral RNA loads were maintained, indicating substantial release of noninfectious particles in vivo. The lack of plasma virion infectivity was associated with a significant post-entry block during early reverse transcription rather than G-to-A hypermutation. The Apobec3-dependent NAb response correlated with IgG binding titers against native, but not detergent-lysed virions. These findings indicate that innate Apobec3 restriction promotes NAb responses by maintaining high concentrations of virions with native B cell epitopes, but in the context of low virion infectivity. Finally, Apobec3 restriction was found to be saturable in vivo, since increasing FV inoculum doses resulted in decreased Apobec3 inhibition. By analogy, maximizing the release of noninfectious particles by modulating APOBEC3 expression may improve humoral immunity against pathogenic human retroviral infections

Expression of infectious murine leukemia viruses by RAW264.7 cells, a potential complication for studies with a widely used mouse macrophage cell line

The mouse macrophage-like cell line RAW264.7, the most commonly used mouse macrophage cell line in medical research, was originally reported to be free of replication-competent murine leukemia virus (MuLV) despite its origin in a tumor induced by Abelson MuLV containing Moloney MuLV as helper virus. As currently available, however, we find that it produces significant levels of ecotropic MuLV with the biologic features of the Moloney isolate and also MuLV of the polytropic or MCF class. Newborn mice developed lymphoma following inoculation with the MuLV mixture expressed by these cells. These findings should be considered in interpretation of increasingly widespread use of these cells for propagation of other viruses, studies of biological responses to virus infection and use in RNA interference and cell signalling studies

Anomalous Dimension and Spatial Correlations in a Point-Island Model

We examine the island size distribution function and spatial correlation function of a model for island growth in the submonolayer regime in both 1 and 2 dimensions. In our model the islands do not grow in shape, and a fixed number of adatoms are added, nucleate, and are trapped at islands as they diffuse. We study the cases of various critical island sizes $i$ for nucleation as a function of initial coverage. We found anomalous scaling of the island size distribution for large $i$ . Using scaling, random walk theory, a version of mean-field theory we obtain a closed form for the spatial correlation function. Our analytic results are verified by Monte Carlo simulations

Paleolimnological Assessment of Six Lakes on the Kissimmee Chain, with Implications for Restoration of the Kissimmee-Okeechobee-Everglades system, Florida, USA

Whitmore TJ, Riedinger-Whitmore MA, Reed ZE, Curtis JH, Yang H, Evans DE, Cropper NR, Alvarado KS, Lauterman FM, Scott A, Leonard CR, Franklin DL. 2020. Paleolimnological assessment of six lakes on the Kissimmee Chain, with implications for restoration of the Kissimmee–Okeechobee–Everglades system, Florida, USA. Lake Reserv Manage. 36:218–242. The Kissimmee Basin in south central Florida contains a large, freshwater network that includes the Kissimmee River and nearly 2 dozen lakes that are headwaters of the Florida Everglades. Management of these lakes is an important part of Everglades restoration. We report a paleolimnological investigation of 6 lakes in the Upper Kissimmee Basin. Engineering activities connected the lakes and permanently altered hydrology in the 19th and 20th centuries. The lakes were naturally meso-eutrophic, but changes in lake levels and nutrient loading contributed to different degrees of eutrophication. Cyanobacteria were present historically at low levels in Lakes East Tohopekaliga, Cypress, and Tohopekaliga, but increased during the 20th century. Lake Jackson lacked cyanobacteria until recently, but Lakes Kissimmee and Marian have had high levels of cyanobacteria since predisturbance times. Profound changes in the lakes occurred after engineering activities eliminated natural large fluctuations in water levels that periodically dried large portions of the basins. Salt-tolerant biological indicators previously alternated with freshwater organisms. Large water-level fluctuations moderated aquatic-plant standing crops and reduced organic matter accumulation. Lakes Kissimmee and Marian showed greatest evidence of former associated wetlands, but lacked large variations in water levels. We recommend disconnecting these lakes from each other and from the Kissimmee River to reestablish large, natural fluctuations in water levels that were part of healthy ecosystem function. Former wetlands should be restored to slow the downstream cascade of nutrients to Lake Okeechobee and the Everglades. This study demonstrates that paleolimnology is useful for assessing hydrological changes that potentially affect lake restoration efforts

A Study of the Type II-P Supernova 2003gd in M74

We present photometric and spectroscopic data of the type II-P supernova 2003gd, which was discovered in M74 close to the end of its plateau phase. SN 2003gd is the first type II supernova to have a directly confirmed red supergiant progenitor. We compare SN 2003gd with SN 1999em, a similar type II-P supernova, and estimate an explosion date of 18th March 2003. We determine a reddening towards the supernova of E(B-V) = 0.14+/-0.06, using three different methods. We also calculate three new distances to M74 of 9.6+/-2.8 Mpc, 7.7+/-1.7 Mpc and 9.6+/-2.2 Mpc. The former was estimated using the Standardised Candle Method (SCM), for type II supernovae, and the latter two using the Brightest Supergiants Method (BSM). When combined with existing kinematic and BSM distance estimates, we derive a mean value of 9.3+/-1.8 Mpc. SN 2003gd was found to have a lower tail luminosity compared to other ``normal'' type II-P SNe bringing into question the nature of this supernova. We present a discussion concluding that this is a ``normal'' type II-P supernova which is consistent with the observed progenitor mass of 8(+4/-2) Mo.Comment: 23 pages, 24 figures to appear in MNRA

Edge-control and surface-smoothness in sub-aperture polishing of mirror segments

This paper addresses two challenges in establishing a new process chain for polishing hexagonal segments for extremely large telescopes:- i) control of edge and corner profiles in small-tool polishing of hexagons, and ii) achieving the required smoothness of the bulk aspheric form. We briefly describe the performance of a CNC-grinding process used to create the off-axis asphere, which established the input-quality for subsequent processing. We then summarize processes for smoothing ground mid-spatials and pre- and corrective polishing using Zeeko CNC machines. The impact of two cases is considered; i) all processing stages are performed after the segment is cut hexagonal, and ii) final rectification of a hexagon after cutting from an aspherised roundel, as an alternative to ionfiguring. We then report on experimental results on witness samples demonstrating edges and corners close to the EELT segment specification, and results on a full-aperture spherical segment showing excellent surface smoothness. © 2012 SPIE

Beings in their own right? Exploring Children and young people's sibling and twin relationships in the Minority World

This paper examines the contributions that the sociological study of sibship and twinship in the Minority World can make to childhood studies. It argues that, in providing one forum within which to explore children and young people's social relationships, we can add to our understanding of children and young people's interdependence and develop a more nuanced understanding of agency. As emergent subjects, children, young people and adults are in a process of ‘becoming’. However, this does not mean that they can ‘become’ anything they choose to. The notion of negotiated interdependence (Punch 2002) is useful in helping us to grasp the contingent nature of children and young people's agency

What we talk about when we talk about "global mindset": managerial cognition in multinational corporations

Recent developments in the global economy and in multinational corporations have placed significant emphasis on the cognitive orientations of managers, giving rise to a number of concepts such as “global mindset” that are presumed to be associated with the effective management of multinational corporations (MNCs). This paper reviews the literature on global mindset and clarifies some of the conceptual confusion surrounding the construct. We identify common themes across writers, suggesting that the majority of studies fall into one of three research perspectives: cultural, strategic, and multidimensional. We also identify two constructs from the social sciences that underlie the perspectives found in the literature: cosmopolitanism and cognitive complexity and use these two constructs to develop an integrative theoretical framework of global mindset. We then provide a critical assessment of the field of global mindset and suggest directions for future theoretical and empirical research

Block sequential adriamycin CMF – optimal non-myeloablative chemotherapy for high risk adjuvant breast cancer?

After the publication of the 10-year survival data from Milan on the adjuvant use of the block sequential regimen consisting of four cycles of adriamycin followed by eight cycles of intravenous CMF, many centres adopted this as standard of care for high risk, multiple node-positive breast cancer. For this reason it was identified as the standard arm for the Anglo-Celtic adjuvant high-dose chemotherapy trial. This study reports on the experience of this regimen in 329 women with early breast cancer involving at least four axillary nodes, who were treated outside any adjuvant chemotherapy trial. At a median follow-up of 3 years, the overall 5-year disease-free survival is 61%, and the overall survival is 70%. These data confirm the efficacy of this regimen in non-trial patients, and, for the same high risk subgroup, indicate that this approach offers an outcome at least as good as that seen in the CALGB 9344 AC-Taxol arm, and the NCIC days 1 and 8 CEF