Review: The Newsletter of the Literary Managers and Dramaturgs of the Americas, volume 16, issue 1

Contents include: Editors\u27 Note; Kirk Watson\u27s List for Making a Cool City; Remembering the Collaboration Project: Texts for an Untitled Bird Play; Mix Tape: A Collaboration; An Untitled Piece; Untitled Baseball Play; Elliott Hayes Remarks 2005; A Newbie at LMDA Conference \u2705, reconstructed journal entries with mostly unforced bildungsroman narrative structure; What\u27s So Great About New Plays? A position paper on the focus on new plays in the field of dramaturgy with three responses; New Plays in Canada, What\u27s So Great About New Plays--A Thought or Seven; Thoughts on New Plays from an Elliott Hayes Award Acceptance Speech. Issue editors: D.J. Hopkins, Shelley Orr, Madeleine Oldhamhttps://soundideas.pugetsound.edu/lmdareview/1032/thumbnail.jp

Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies

Multimodal imaging needle combining optical coherence tomography and fluorescence for imaging of live breast cancer cells labeled with a fluorescent analog of tamoxifen

Significance: Imaging needles consist of highly miniaturized focusing optics encased within a hypodermic needle. The needles may be inserted tens of millimeters into tissue and have the potential to visualize diseased cells well beyond the penetration depth of optical techniques applied externally. Multimodal imaging needles acquire multiple types of optical signals to differentiate cell types. However, their use has not previously been demonstrated with live cells.Aim: We demonstrate the ability of a multimodal imaging needle to differentiate cell types through simultaneous optical coherence tomography (OCT) and fluorescence imaging.Approach: We characterize the performance of a multimodal imaging needle. This is paired with a fluorescent analog of the therapeutic drug, tamoxifen, which enables cell-specific fluorescent labeling of estrogen receptor-positive (ER+) breast cancer cells. We perform simultaneous OCT and fluorescence in situ imaging on MCF-7 ER+ breast cancer cells and MDA-MB-231 ER-cells. Images are compared against unlabeled control samples and correlated with standard confocal microscopy images.Results: We establish the feasibility of imaging live cells with these miniaturized imaging probes by showing clear differentiation between cancerous cells.Conclusions: Imaging needles have the potential to aid in the detection of specific cancer cells within solid tissue

Plant-made vaccines in support of the Millennium Development Goals

Vaccines are one of the most successful public health achievements of the last century. Systematic immunisation programs have reduced the burden of infectious diseases on a global scale. However, there are limitations to the current technology, which often requires costly infrastructure and long lead times for production. Furthermore, the requirement to keep vaccines within the cold-chain throughout manufacture, transport and storage is often impractical and prohibitively expensive in developing countries—the very regions where vaccines are most needed. In contrast, plant-made vaccines (PMVs) can be produced at a lower cost using basic greenhouse agricultural methods, and do not need to be kept within such narrow temperature ranges. This increases the feasibility of developing countries producing vaccines locally at a small-scale to target the specific needs of the region. Additionally, the ability of plant-production technologies to rapidly produce large quantities of strain-specific vaccine demonstrates their potential use in combating pandemics. PMVs are a proven technology that has the potential to play an important role in increasing global health, both in the context of the 2015 Millennium Development Goals and beyond

Investigation of Association between PFO Complicated by Cryptogenic Stroke and a Common Variant of the Cardiac Transcription Factor GATA4

Patent foramen ovale (PFO) is associated with clinical conditions including cryptogenic stroke, migraine and varicose veins. Data from studies in humans and mouse suggest that PFO and the secundum form of atrial septal defect (ASDII) exist in an anatomical continuum of septal dysmorphogenesis with a common genetic basis. Mutations in multiple members of the evolutionarily conserved cardiac transcription factor network, including GATA4, cause or predispose to ASDII and PFO. Here, we assessed whether the most prevalent variant of the GATA4 gene, S377G, was significantly associated with PFO or ASD. Our analysis of world indigenous populations showed that GATA4 S377G was largely Caucasian-specific, and so subjects were restricted to those of Caucasian descent. To select for patients with larger PFO, we limited our analysis to those with cryptogenic stroke in which PFO was a subsequent finding. In an initial study of Australian subjects, we observed a weak association between GATA4 S377G and PFO/Stroke relative to Caucasian controls in whom ASD and PFO had been excluded (OR = 2.16; p = 0.02). However, in a follow up study of German Caucasians no association was found with either PFO or ASD. Analysis of combined Australian and German data confirmed the lack of a significant association. Thus, the common GATA4 variant S377G is likely to be relatively benign in terms of its participation in CHD and PFO/Stroke

Search for lepton flavor violating decays of a heavy neutral particle in p-pbar collisions at root(s)=1.8 TeV

We report on a search for a high mass, narrow width particle that decays directly to e+mu, e+tau, or mu+tau. We use approximately 110 pb^-1 of data collected with the Collider Detector at Fermilab from 1992 to 1995. No evidence of lepton flavor violating decays is found. Limits are set on the production and decay of sneutrinos with R-parity violating interactions.Comment: Figure 2 fixed. Reference 4 fixed. Minor changes to tex

Search for Kaluza-Klein Graviton Emission in ppˉp\bar{p} Collisions at s=1.8\sqrt{s}=1.8 TeV using the Missing Energy Signature

We report on a search for direct Kaluza-Klein graviton production in a data sample of 84 ${pb}^{-1}$ of \ppb collisions at $\sqrt{s}$ = 1.8 TeV, recorded by the Collider Detector at Fermilab. We investigate the final state of large missing transverse energy and one or two high energy jets. We compare the data with the predictions from a $3+1+n$-dimensional Kaluza-Klein scenario in which gravity becomes strong at the TeV scale. At 95% confidence level (C.L.) for $n$=2, 4, and 6 we exclude an effective Planck scale below 1.0, 0.77, and 0.71 TeV, respectively.Comment: Submitted to PRL, 7 pages 4 figures/Revision includes 5 figure

Joint hypermobility in children with idiopathic scoliosis: SOSORT award 2011 winner

<p>Abstract</p> <p>Background</p> <p>Generalized joint hypermobility (JHM) refers to increased joint mobility with simultaneous absence of any other systemic disease. JHM involves proprioception impairment, increased frequency of pain within joints and tendency to injure soft tissues while performing physical activities. Children with idiopathic scoliosis (IS) often undergo intensive physiotherapy requiring good physical capacities. Further, some physiotherapy methods apply techniques that increase joint mobility and thus may be contraindicated.</p> <p>The aim of this paper was to assess JHM prevalence in children with idiopathic scoliosis and to analyze the relationship between JHM prevalence and the clinical and radiological parameters of scoliosis. The methods of assessment of generalized joint hypermobility were also described.</p> <p>Materials and methods</p> <p>This case-control study included 70 subjects with IS, aged 9-18 years (mean 13.2 ± 2.2), Cobb angle range 10°-53° (mean 24.3 ± 11.7), 34 presenting single curve thoracic scoliosis and 36 double curve thoracic and lumbar scoliosis. The control group included 58 children and adolescents aged 9-18 years (mean 12.6 ± 2.1) selected at random. The presence of JHM was determined using Beighton scale complemented with the questionnaire by Hakim and Grahame. The relationship between JHM and the following variables was evaluated: curve severity, axial rotation of the apical vertebra, number of curvatures (single versus double), number of vertebrae within the curvature (long versus short curves), treatment type (physiotherapy versus bracing) and age.</p> <p>Statistical analysis was performed with Statistica 8.1 (StatSoft, USA). The Kolmogorov-Smirnov test, U Mann-Whitney test, Chi²test, Pearson and Spermann correlation rank were conducted. The value <it>p </it>= 0.05 was adopted as the level of significance.</p> <p>Results</p> <p>JHM was diagnosed in more than half of the subjects with idiopathic scoliosis (51.4%), whilst in the control group it was diagnosed in only 19% of cases (<it>p </it>= 0.00015). A significantly higher JHM prevalence was observed in both girls (<it>p </it>= 0.0054) and boys (<it>p </it>= 0.017) with IS in comparison with the corresponding controls. No significant relation was found between JHM prevalence and scoliosis angular value (<it>p </it>= 0.35), apical vertebra rotation (<it>p </it>= 0.86), the number of vertebrae within curvature (<it>p </it>= 0.8), the type of applied treatment (<it>p </it>= 0.55) and the age of subjects (<it>p </it>= 0.79). JHM prevalence was found to be higher in children with single curve scoliosis than in children with double curve scoliosis (<it>p </it>= 0.03).</p> <p>Conclusions</p> <p>JHM occurs more frequently in children with IS than in healthy sex and age matched controls. No relation of JHM with radiological parameters, treatment type and age was found. Systematically searched in IS children, JHM should be taken into account when physiotherapy is planned.</p

Metformin mitigates the impaired development of skeletal muscle in the offspring of obese mice

Background: Maternal obesity is linked with offspring obesity and type 2 diabetes. Skeletal muscle (SM) insulin resistance is central to the development of diabetes. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is inhibited in SM of fetuses born to obese mothers