Some consequences of intense electromagnetic wave injection into space plasmas

The future possibility of actively testing the current understanding of how energetic particles may be accelerated in space or dumped from the radiation belts using intense electromagnetic energy from ground based antennas is discussed. The ground source of radiation is merely a convenience. A space station source for radiation that does not have to pass through the atmosphere and lower ionosphere, is an attractive alternative. The text is divided into two main sections addressing the possibilities of: (1) accelerating electrons to fill selected flux tubes above the Kennel-Petscheck limit for stably trapped fluxes, and (2) using an Alfven maser to cause rapid depletion of energetic protons or electrons from the radiation belts

Intrathecal Aav9.trastuzumab Tumor Prophylaxis And Treatment In A Murine Xenograft Model Of Her2+ Breast Cancer Brain Metastases

Breast cancer brain metastases (BCBM) are a deadly sequela of breast tumors that overexpress human epidermal growth factor receptor 2 (HER2). HER2+ BCBM affects approximately 17,000 women in the US every year. Median survival is 10-13 months from the time of diagnosis of central nervous system (CNS) disease. Current therapeutic interventions are invasive, toxic, and largely ineffective, leaving a clear, unmet need for targeted HER2+ BCBM treatments. Trastuzumab(Herceptin®) is a monoclonal antibody used to treat HER2+ breast cancer successfully, but systemic trastuzumab cannot bypass the blood-brain barrier (BBB). To solve this problem, we have developed an adeno-associated virus serotype 9 (AAV9) vector to express trastuzumab in vivo after a single intrathecal (IT) injection. IT vector administration in an orthotopic Rag1-/- murine xenograft model of HER2+ BCBM led to a significant increase in median survival and attenuated brain tumor growth. We also report preservation of both the HER2 antigen specificity and the natural killer (NK) cell-associated mechanism of action of trastuzumab. Finally, we demonstrate increased median survival when IT AAV9.trastuzumab is administered as tumor treatment. Our results indicate that IT AAV9.trastuzumab may provide significant anti-tumor activity in patients with HER2+ BCBM

LGBTQ Inequality in Engineering Education

BackgroundResearchers over the past three decades have documented processes of gender and racial/ethnic inequality in engineering education but little is known about other axes of difference, including the experiences of lesbian, gay, bisexual, transgender, and queer (LGBTQ) persons in engineering. Despite growing interest in LGBTQ inequality generally, prior research has yet to systematically document day‐to‐day experiences of inequality in engineering education along LGBTQ status.Purpose/HypothesisIn this article, we use survey data from students enrolled in eight universities to examine LGBTQ inequality in engineering education. Specifically, we explore whether LGBTQ students experience greater marginalization than their classmates, whether their engineering work is more likely to be devalued, and whether they experience more negative health and wellness outcomes. We hypothesize that LGBTQ students experience greater marginalization and devaluation and more negative health and wellness outcomes compared to their non‐LGBTQ peers.Data/MethodWe analyzed novel survey data from 1,729 undergraduate students (141 of whom identify as LGBTQ) enrolled in eight U.S. engineering programs.ResultsWe found that LGBTQ students face greater marginalization, devaluation, and health and wellness issues relative to their peers, and that these health and wellness inequalities are explained in part by LGBTQ students’ experiences of marginalization and devaluation in their engineering programs. Furthermore, there is little variation in the climate for LGBTQ students across the eight schools, suggesting that anti‐LGBTQ bias may be widespread in engineering education.ConclusionsWe call for reflexive research on LGBTQ inequality in engineering education and the institutional and cultural shifts needed to mitigate these processes and better support LGBTQ students.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146822/1/jee20239.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146822/2/jee20239_am.pd

Professionally Queer: Queer Men and the World of Work

In the past decade, scholars and the public have increasingly paid attention to queer populations and their experiences in the workforce. Yet, little work has been done to understand the meaning that queer men attribute to their sexuality in shaping their career decisions and experiences, leaving unanswered how and under what conditions sexuality consequentially influences queer men’s career decisions and experiences. Using data from 67 in-depth interviews with college-educated queer men living and working in the New York City Metropolitan Area, this dissertation examines how queer men make sense of their career-related decisions, attempts at securing employment, and their experiences once in the workforce as well as what role they believe their sexuality played in shaping these decisions and experiences. The central argument of this project is that the role that respondents believe their sexuality played in influencing career decisions and continues to play in shaping their experiences in the workforce is largely dependent on the perceived boundary brightness, or symbolic significance, surrounding or attributed to their sexuality; additionally, an individual’s boundary brightness is subject to change across stages in one’s career narrative. This boundary brightness was shaped by both how meaningful and consequential respondents believed their sexuality to be during a given career stage and how central their sexuality was to their self-conception. I break respondents into 4 groups based on boundary brightness across the three stages in their career narratives (career-related decisions, the labor market, and the workforce). The first is the Consistently Bright group—for whom sexuality meaningfully influenced their career decisions, experiences on the labor market, and how they navigated the workforce. The second group, the Dimmed Boundaries group, believed that their sexuality shaped their career decisions but not as something that they had to manage on the labor market or in the workforce. The third group, the Brightened Boundaries group, did not see their sexuality as something that shaped their career-related decisions but as something that shaped their experiences either on the labor market or in the workforce. Lastly, those in the Never Bright group did not perceive their sexuality as meaningfully shaping their decisions or experiences at any stage of their career narratives. Further, these findings highlight both the centrality of masculinity in queer men’s career narratives and the inadequacy of a categorical approach in examinations of sexuality and the sphere of work. I conclude by discussing what these findings can contribute to scholarly and public understandings of (sexual) identity and work and highlight potential avenues for future research.PHDSociologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/166122/1/wrroth_1.pd

Randomised controlled trial of a Calcium Channel or Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker Regime to Reduce Blood Pressure Variability following Ischaemic Stroke (CAARBS): a protocol for a feasibility study

Introduction Raised blood pressure (BP) is common after stroke and is associated with a poor prognosis, yet trials of BP lowering in the immediate poststroke period have not demonstrated a benefit. One possible explanation for this may be that BP variability (BPV) rather than absolute levels predicts outcome, as BPV is increased after stroke and is associated with poor outcomes. Furthermore, there is evidence of distinct antihypertensive class effects on BPV despite similar BP-lowering effects. However, whether BPV in the immediate poststroke period is a therapeutic target has not been prospectively investigated. The objectives of this trial are to assess the feasibility and safety of recruiting patients following an acute ischaemic stroke or transient ischaemic attack (TIA) to an interventional randomised controlled trial comparing the effects of two different antihypertensive drug classes on BPV. Secondary exploratory objectives are to assess if different therapeutic strategies have diverse effects on levels of BPV and if this has an impact on outcomes. Methods 150 adult patients with first-ever ischaemic stroke or TIA who require antihypertensive therapy for secondary prevention will be recruited within 7 days of the event from stroke services across three sites. After baseline assessments they will be randomly assigned to treatment with a calcium channel blocker or ACE inhibitor/angiotensin receptor blocker-based regimen and followed up for a period of three months. Ethics and dissemination Ethical and regulatory approvals have been granted. Dissemination is planned via publication in peer-reviewed medical journals and presentation at relevant conferences. Trial registration number ISRCTN10853487

Modulation of frontal effective connectivity during speech

Noninvasive neurostimulation methods such as transcranial direct current stimulation (tDCS) can elicit long-lasting, polarity-dependent changes in neocortical excitability. In a previous concurrent tDCS-fMRI study of overt picture naming, we reported significant behavioural and regionally specific neural facilitation effects in left inferior frontal cortex (IFC) with anodal tDCS applied to left frontal cortex (Holland et al., 2011). Although distributed connectivity effects of anodal tDCS have been modelled at rest, the mechanism by which 'on-line' tDCS may modulate neuronal connectivity during a task-state remains unclear. Here, we used Dynamic Causal Modelling (DCM) to determine: (i) how neural connectivity within the frontal speech network is modulated during anodal tDCS; and, (ii) how individual variability in behavioural response to anodal tDCS relates to changes in effective connectivity strength. Results showed that compared to sham, anodal tDCS elicited stronger feedback from inferior frontal sulcus (IFS) to ventral premotor (VPM) accompanied by weaker self-connections within VPM, consistent with processes of neuronal adaptation. During anodal tDCS individual variability in the feedforward connection strength from IFS to VPM positively correlated with the degree of facilitation in naming behaviour. These results provide an essential step towards understanding the mechanism of 'online' tDCS paired with a cognitive task. They also identify left IFS as a 'top-down' hub and driver for speech change

The RGS gene loco is essential for male reproductive system differentiation in Drosophila melanogaster

<p>Abstract</p> <p>Background</p> <p>The <it>loco </it>gene encodes several different isoforms of a regulator of G-protein signalling. These different isoforms of LOCO are part of a pathway enabling cells to respond to external signals. LOCO is known to be required at various developmental stages including neuroblast division, glial cell formation and oogenesis. Less is known about LOCO and its involvement in male development therefore to gain further insight into the role of LOCO in development we carried out a genetic screen and analysed males with reduced fertility.</p> <p>Results</p> <p>We identified a number of lethal <it>loco </it>mutants and four semi-lethal lines, which generate males with reduced fertility. We have identified a fifth <it>loco </it>transcript and show that it is differentially expressed in developing pupae. We have characterised the expression pattern of all <it>loco </it>transcripts during pupal development in the adult testes, both in wild type and <it>loco </it>mutant strains. In addition we also show that there are various G-protein α subunits expressed in the testis all of which may be potential binding partners of LOCO.</p> <p>Conclusion</p> <p>We propose that the male sterility in the new <it>loco </it>mutants result from a failure of accurate morphogenesis of the adult reproductive system during metamorphosis, we propose that this is due to a loss of expression of <it>loco c3</it>. Thus, we conclude that specific isoforms of <it>loco </it>are required for the differentiation of the male gonad and genital disc.</p

Nondestructive Electromagnetic Material Characterization using a Dual Waveguide Probe: A Full Wave Solution

A nondestructive technique for determining the complex permittivity and permeability of a perfect electric conductor backed magnetic shielding material using a dual waveguide probe is presented. The dual waveguide probe allows for the simultaneous collection of reflection and transmission coefficients which distinguishes it from single probe methods common in the literature. Theoretical development of these coefficients, which is accomplished through a coupled magnetic field integral equations formulation using Love\u27s equivalence principle and solved via the method of moments (MOM), is discussed. Evaluation of the resulting MOM impedance matrix elements is performed using complex plane integration leading to enhanced computational efficiency and physical insight. Comparison of the theoretical and measured reflection and transmission coefficients using a root finding algorithm leads to the desired permittivity and permeability. Measurement results of a magnetic shielding material are presented and compared to traditional methods for the purpose of validating the new technique. The probe\u27s sensitivity to aperture alignment, sample thickness, and flange thickness is also investigated.Abstract © AGU

Gravimetric phenotyping of whole plant transpiration responses to atmospheric vapour pressure deficit identifies genotypic variation in water use efficiency

There is increasing interest in rapidly identifying genotypes with improved water use efficiency, exemplified by the development of whole plant phenotyping platforms that automatically measure plant growth and water use. Transpirational responses to atmospheric vapour pressure deficit (VPD) and whole plant water use efficiency (WUE, defined as the accumulation of above ground biomass per unit of water used) were measured in 100 maize (Zea mays L.) genotypes. Using a glasshouse based phenotyping platform with naturally varying VPD (1.5 to 3.8 kPa), a 2-fold variation in WUE was identified in well-watered plants. Regression analysis of transpiration versus VPD under these conditions, and subsequent whole plant gas exchange at imposed VPDs (0.8 to 3.4 kPa) showed identical responses in specific genotypes. Genotype response of transpiration versus VPD fell into two categories: 1) a linear increase in transpiration rate with VPD with low (high WUE) or high (low WUE) transpiration rate at all VPDs, 2) a non-linear response with a pronounced change point at low VPD (high WUE) or high VPD (low WUE). In the latter group, high WUE genotypes required a significantly lower VPD before transpiration was restricted, and had a significantly lower rate of transpiration in response to VPD after this point, when compared to low WUE genotypes. Change point values were significantly positively correlated with stomatal sensitivity to VPD. A change point in stomatal response to VPD may explain why some genotypes show contradictory WUE rankings according to whether they are measured under glasshouse or field conditions. Furthermore, this novel use of a high throughput phenotyping platform successfully reproduced the gas exchange responses of individuals measured in whole plant chambers, accelerating the identification of plants with high WUE

Actin cytoskeleton remodeling during early Drosophila furrow formation requires recycling endosomal components Nuclear-fallout and Rab11

Cytokinesis requires a dramatic remodeling of the cortical cytoskeleton as well as membrane addition. The Drosophila pericentrosomal protein, Nuclear-fallout (Nuf), provides a link between these two processes. In nuf-derived embryos, actin remodeling and membrane recruitment during the initial stages of metaphase and cellular furrow formation are disrupted. Nuf is a homologue of arfophilin-2, an ADP ribosylation factor effector that binds Rab11 and influences recycling endosome (RE) organization. Here, we show that Nuf is an important component of the RE, and that these phenotypes are a consequence of Nuf activities at the RE. Nuf exhibits extensive colocalization with Rab11, a key RE component. GST pull-downs and the presence of a conserved Rab11-binding domain in Nuf demonstrate that Nuf and Rab11 physically associate. In addition, Nuf and Rab11 are mutually required for their localization to the RE. Embryos with reduced levels of Rab11 produce membrane recruitment and actin remodeling defects strikingly similar to nuf-derived embryos. These analyses support a common role for Nuf and Rab11 at the RE in membrane trafficking and actin remodeling during the initial stages of furrow formation