The Orbit of the Companion to HD 100453A: Binary-Driven Spiral Arms in a Protoplanetary Disk

HD 100453AB is a 10+/-2 Myr old binary whose protoplanetary disk was recently revealed to host a global two-armed spiral structure. Given the relatively small projected separation of the binary (1.05", or ~108 au), gravitational perturbations by the binary seemed to be a likely driving force behind the formation of the spiral arms. However, the orbit of these stars remained poorly understood, which prevented a proper treatment of the dynamical influence of the companion on the disk. We observed HD 100453AB between 2015-2017 utilizing extreme adaptive optics systems on the Very Large Telescope and Magellan Clay Telescope. We combined the astrometry from these observations with published data to constrain the parameters of the binary's orbit to a=1.06"+/-0.09", e=0.17+/-0.07, and i=32.5+/- 6.5 degrees. We utilized publicly available ALMA CO data to constrain the inclination of the disk to i~28 degrees, which is relatively co-planar with the orbit of the companion and consistent with previous estimates from scattered light images. Finally, we input these constraints into hydrodynamical and radiative transfer simulations to model the structural evolution of the disk. We find that the spiral structure and truncation of the circumprimary disk in HD 100453 are consistent with a companion-dirven origin. Furthermore, we find that the primary star's rotation, its outer disk, and the companion exhibit roughly the same direction of angular momentum, and thus the system likely formed from the same parent body of material.Comment: 28 pages, 11 figures, Accepted to Ap

Proteomic analysis of the processes leading to Madurella mycetomatis grain formation in Galleria mellonella larvae

Mycetoma is a neglected chronic and granulomatous infection primarily associated with the fungal pathogen Madurella mycetomatis. Characteristic of this infection is the formation of grains. However, the processes leading to grain formation are not known. In this study, we employed a proteomic approach to characterise M. mycetomatis grain formation in Galleria mellonella larvae and map the processes leading to grain formation over time. For this, at 1 day, 3 days and 7 days post-inoculation, proteins from grains and hemolymph were extracted and analysed by label-free mass spectrometry. A total of 87, 51 and 48 M. mycetomatis proteins and 713, 997, 18 G. mellonella proteins were found in grains on day 1, 3 and 7 post-inoculation respectively. M. mycetomatis proteins were mainly involved in cellular metabolic processes and numerous enzymes were encountered. G. mellonella proteins were primarily involved in the nodulation process. The proteins identified were linked to nodulation and grain formation and four steps of grain formation were identified. The results of this proteomic approach could in the future be used to design novel strategies to interfere with mycetoma grain formation and to combat this difficult to treat infection

Junctional diversification in the generation of the precursor of a discrete immune response

Phosphocholine (PC)-specific antibodies that arise in the mouse in response to Proteus morganii (PM) and use V1-DFL16.1-JH1 are characterized by a number of recurring mutations. Most striking is an invariant A for G substitution in codon 95 of VH which results in an asparagine instead of aspartate at that position. Because of the apparent importance of this substitution in an anti-PC(PM) response, we wanted to determine the molecular basis for this base change. A cDNA library derived from pre-immune splenic B cells was examined for the frequency of VDJ containing the A substitution at 95 and the presence of additional point mutations in these sequences. Six different cDNA were isolated which contained an A substitution at the VD junction (frequency 0.00009); a seventh positive cDNA could not be examined. The V segments of four of these cDNA matched known germline genes and were, therefore, unmutated. Two others closely matched V in families whose members have not all been characterized, hence, it is not known whether the mutations observed are somatic or germline in origin. Sequences of 35 cDNA clones, containing the same V segment but differing in D, J and junctional nucleotides, revealed no mutations. These results indicate that the A substitution generated at codon 95 is most likely a product of V-DJ joining.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30952/1/0000624.pd

Adoptive Immunotherapy with Cytokine-Induced Killer Cells for Patients with Relapsed Hematologic Malignancies after Allogeneic Hematopoietic Cell Transplantation

Donor leukocyte infusions induce remissions in some patients with hematologic malignancies who relapse after allogeneic hematopoietic cell transplantation (HCT); however, graft-versus-host disease (GVHD) remains the major complication of this strategy. Cytokine-induced killer (CIK) cells are a unique population of cytotoxic T lymphocytes that express the CD3+CD56+ phenotype and show marked up-regulation of the natural killer cell receptor NKG2D (CD314). CIK cells are non–major histocompatibility complex–restricted and NKG2D-dependent in target recognition and cytotoxicity. We explored the feasibility of ex vivo expansion of allogeneic CIK cells in patients with relapsed hematologic malignancies after allogeneic HCT. Eighteen patients (median age, 53 years; range, 20-69 years) received CIK cell infusions at escalating doses of 1 × 107 CD3+ cells/kg (n = 4), 5 × 107 CD3+ cells/kg (n = 6), and 1 × 108 CD3+ cells/kg (n = 8). The median expansion of CD3+ cells was 12-fold (range, 4- to 91-fold). CD3+CD56+ cells represented a median of 11% (range, 4%-44%) of the harvested cells, with a median 31-fold (range, 7- to 515-fold) expansion. Median CD3+CD314+ cell expression was 53% (range, 32%-78%) of harvested cells. Significant cytotoxicity was demonstrated in vitro against a panel of human tumor cell lines. Acute GVHD grade I-II was seen in 2 patients, and 1 patient had limited chronic GVHD. After a median follow-up of 20 months (range, 1-69 months) from CIK infusion, the median overall survival was 28 months, and the median event-free survival was 4 months. All deaths were due to relapsed disease; however, 5 patients had longer remissions after infusion of CIK cells than from allogeneic HCT to relapse. Our findings indicate that this form of adoptive immunotherapy is well tolerated and induces a low incidence of GVHD, supporting further investigation as an upfront modality to enhance graft-versus-tumor responses in high-risk patient populations

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

Structural and electronic properties of polycrystalline InAs thin films deposited on silicon dioxide and glass at temperatures below 500 °c

Polycrystalline indium arsenide (poly InAs) thin films grown at 475 °C by metal organic vapor phase epitaxy (MOVPE) are explored as possible candidates for low-temperature-grown semiconducting materials. Structural and transport properties of the films are reported, with electron mobilities of ~100 cm2/V·s achieved at room temperature, and values reaching 155 cm2/V·s for a heterostructure including the polycrystalline InAs film. Test structures fabricated with an aluminum oxide (Al2O3) top-gate dielectric show that transistor-type behavior is possible when poly InAs films are implemented as the channel material, with maximum ION/IOFF > 250 achieved at −50 °C and ION/IOFF = 90 at room temperature. Factors limiting the ION/IOFF ratio are investigated and recommendations are made for future implementation of this material

Cardiorespiratory fitness is associated with physical literacy in a large sample of Canadian children aged 8 to 12 years

Background The associations between cardiorespiratory fitness (CRF) and physical literacy in children are largely unknown. The aim of this study was to assess the relationships between CRF, measured using the 20-m shuttle run test (20mSRT), and components of physical literacy among Canadian children aged 8–12 years. Methods A total of 9393 (49.9% girls) children, with a mean (SD) age of 10.1 (±1.2) years, from a cross-sectional surveillance study were included for this analysis. The SRT was evaluated using a standardized 15 m or 20 m protocol. All 15 m SRTs were converted to 20mSRT values using a standardized formula. The four domains of physical literacy (Physical Competence, Daily Behaviour, Motivation and Confidence, and Knowledge and Understanding) were measured using the Canadian Assessment of Physical Literacy. Tertiles were identified for 20mSRT laps, representing low, medium, and high CRF for each age and gender group. Cohen’s d was used to calculate the effect size between the low and high CRF groups. Results CRF was strongly and favourably associated with all components of physical literacy among school-aged Canadian children. The effect size between low and high CRF tertile groups was large for the Physical Competence domain (Cohen’s d range: 1.11–1.94) across age and gender groups, followed by moderate to large effect sizes for Motivation and Confidence (Cohen’s d range: 0.54–1.18), small to moderate effect sizes for Daily Behaviour (Cohen’s d range: 0.25–0.81), and marginal to moderate effect sizes for Knowledge and Understanding (Cohen’s d range: 0.08–0.70). Conclusions This study identified strong favourable associations between CRF and physical literacy and its constituent components in children aged 8–12 years. Future research should investigate the sensitivity and specificity of the 20mSRT in screening those with low physical literacy levels

Definitions, Foundations and Associations of Physical Literacy: A Systematic Review

Background: The concept of physical literacy has stimulated increased research attention in recent years—being deployed in physical education, sport participation, and the promotion of physical activity. Independent research groups currently operationalize the construct differently. Objective The purpose of this systematic review was to conduct a systematic review of the physical literacy construct,as reflected in contemporary research literature. Methods: Five databases were searched using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines for systematic reviews. Inclusion criteria were English language, peer reviewed, published by March 2016, and seeking to conceptualize physical literacy. Articles that met these criteria were analysed in relation to three core areas: properties/attributes, philosophicalfoundations and theoretical associations with other constructs. A total of 50 published articles met the inclusion criteria and were analysed qualitatively using inductive thematic analysis.Results: The thematic analysis addressed the three core areas. Under definitions, core attributes that define physical literacy were identified, as well as areas of conflict between different approaches currently being adopted. One relatively clear philosophical approach was prominent in approximately half of the papers, based on a monist/holistic ontology and phenomenological epistemology. Finally, theanalysis identified a number of theoretical associations, including health, physical activity and academic performance.Conclusions: Current literature contains different representations of the physical literacy construct. The costs and benefits of adopting an exclusive approach versus pluralism are considered. Recommendations for both researchers and practitioners focus on identifying and clearly articulating the definitions, philosophical assumptions and expected outcomes prior to evaluating the effectiveness of this emerging concept

Endogenous Bax Translocation in SH-SY5Y Human Neuroblastoma Cells and Cerebellar Granule Neurons Undergoing Apoptosis

Changes at the mitochondria are an early, required step in apoptosis in various cell types. We used western blot analysis to demonstrate that the proapoptotic protein Bax translocated from the cytosolic to the mitochondrial fraction in SH-SY5Y human neuroblastoma cells undergoing staurosporine- or EGTA-mediated apoptosis. Levels of mitochondrial Bax increased 15 min after staurosporine treatment. In EGTA-treated cells, increased levels of mitochondrial Bax were seen at 4 h, consistent with a slower onset of apoptosis in EGTA versus staurosporine treatments. We also demonstrate the concomitant translocation of cytochrome c from the mitochondrial to the cytosolic fractions. We correlated these translocations with changes in caspase-3-like activity. An increase in caspase-3-like activity was evident 2 h after staurosporine treatment. Inhibition of the mitochondrial permeability transition had no effect on Bax translocation or caspase-3-like activity in staurosporine-treated SH-SY5Y cells. In primary cultures of cerebellar granule neurons undergoing low K + -mediated apoptosis, Bax translocation to the mitochondrial fraction was evident at 3 h. Cytochrome c release into the cytosol was not significant until 8 h after treatment. These data support a model of apoptosis in which Bax acts directly at the mitochondria to allow the release of cytochrome c.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66150/1/j.1471-4159.1999.0721899.x.pd

Claudin-7 Is Frequently Overexpressed in Ovarian Cancer and Promotes Invasion

Background: Claudins are tight junction proteins that are involved in tight junction formation and function. Previous studies have shown that claudin-7 is frequently upregulated in epithelial ovarian cancer (EOC) along with claudin-3 and claudin-4. Here, we investigate in detail the expression patterns of claudin-7, as well as its possible functions in EOC. Methodology/Principal Findings: A total of 95 ovarian tissue samples (7 normal ovarian tissues, 65 serous carcinomas, 11 clear cell carcinomas, 8 endometrioid carcinomas and 4 mucinous carcinomas) were studied for claudin-7 expression. In real-time RT-PCR analysis, the gene for claudin-7, CLDN7, was found to be upregulated in all the tumor tissue samples studied. Similarly, immunohistochemical analysis and western blotting showed that claudin-7 protein was significantly overexpressed in the vast majority of EOCs. Small interfering RNA-mediated knockdown of claudin-7 in ovarian cancer cells led to significant changes in gene expression as measured by microarrays and validated by RT-PCR and immunoblotting. Analyses of the genes differentially expressed revealed that the genes altered in response to claudin-7 knockdown were associated with pathways implicated in various molecular and cellular functions such as cell cycle, cellular growth and proliferation, cell death, development, and cell movement. Through functional experiments in vitro, we found that both migration and invasion were altered in cells where CLDN7 had been knocked down or overexpressed. Interestingly, claudin-7 expression was associated with a net increase in invasion, but also with a decrease in migration