Transparent and Flexible Thin Film Electroluminescent Devices Using HiTUS Deposition and Laser Processing Fabrication

Highly transparent thin film electroluminescent structures offering excellent switch on characteristics, high luminance and large break-down voltages have been deposited onto glass and flexible polymeric materials with no substrate heating using high target utilization sputtering. Deposition of ZnS:Mn as the active light emitting layer and Y2O3,Al2O3,Ta2O5, and HfO2 as dielectric materials arranged in single and multiple layer configurations were investigated. Devices incorporating Al2O3,HfO2 quadruple layers demonstrate the highest attainable luminance at low threshold voltage. Single pulse excimer laser irradiation of the phosphor layer prior to deposition of the top dielectric layer enhanced the luminance of the devices. The devices fabricated on glass and polymeric substrates exhibited a maximum luminance of 500 and 450 cdm−2 when driven at 270 VRMS and 220 VRMS, respectively, with a 1.0 kHz sine wave

Clinical Utility of Cardiovascular Magnetic Resonance Imaging for Diagnosis of Acute Myocarditis

A 49 year-old patient with past medical history significant for arterial hypertension (treated with telmisartan 80 mg daily), presented to the emergency department with 18-hour gastric discomfort and fatigue. Five days prior to this presentation the patient had an episode of febrile gastroenteritis. The evening prior to presentation the patient had blood chemistries performed at an outside institution, where an increase of myocardial enzymes (troponin and CPK-MB) were noted. On presentation the patient was uncomfortable due to abdominal pain, but the clinical examination was almost normal. Blood pressure was 150/80 mmHg and heart rate was 60 beats/min. Cardiac S1 and S2 sounds where audible, without additional cardiac tones, murmurs, pericardial or pleural friction. There was no jugular venous distention, rales or peripheral edema present. Admission 12-lead electrocardiogram (ECG) demonstrated normal sinus rhythm with a rate of 60 beats/min, and early repolarization pattern with a slight J-point elevation in the lateral leads (I, aVL, V5, V6)

Clinical Utility of Cardiovascular Magnetic Resonance Imaging for Diagnosis of Acute Myocarditis

Cardiac magnetic resonance imaging (CMR) is a novel imaging technique that may help differentiate between myocarditis and acute coronary syndrome and compares favorably to other imaging techniques because it also provides information on tissue consistency and characteristics. We herein present a case, whereby CMR was most useful in providing such a differential diagnosis

In Vivo Analysis of the Notch Receptor S1 Cleavage

A ligand-independent cleavage (S1) in the extracellular domain of the mammalian Notch receptor results in what is considered to be the canonical heterodimeric form of Notch on the cell surface. The in vivo consequences and significance of this cleavage on Drosophila Notch signaling remain unclear and contradictory. We determined the cleavage site in Drosophila and examined its in vivo function by a transgenic analysis of receptors that cannot be cleaved. Our results demonstrate a correlation between loss of cleavage and loss of in vivo function of the Notch receptor, supporting the notion that S1 cleavage is an in vivo mechanism of Notch signal control

Notch Lineages and Activity in Intestinal Stem Cells Determined by a New Set of Knock-In Mice

The conserved role of Notch signaling in controlling intestinal cell fate specification and homeostasis has been extensively studied. Nevertheless, the precise identity of the cells in which Notch signaling is active and the role of different Notch receptor paralogues in the intestine remain ambiguous, due to the lack of reliable tools to investigate Notch expression and function in vivo. We generated a new series of transgenic mice that allowed us, by lineage analysis, to formally prove that Notch1 and Notch2 are specifically expressed in crypt stem cells. In addition, a novel Notch reporter mouse, Hes1-EmGFPSAT, demonstrated exclusive Notch activity in crypt stem cells and absorptive progenitors. This roster of knock-in and reporter mice represents a valuable resource to functionally explore the Notch pathway in vivo in virtually all tissues

Genetic Circuitry of Survival Motor Neuron, the Gene Underlying Spinal Muscular Atrophy

The clinical severity of the neurodegenerative disorder spinal muscular atrophy (SMA) is dependent on the levels of functional Survival Motor Neuron (SMN) protein. Consequently, current strategies for developing treatments for SMA generally focus on augmenting SMN levels. To identify additional potential therapeutic avenues and achieve a greater understanding of SMN, we applied in vivo, in vitro, and in silico approaches to identify genetic and biochemical interactors of the Drosophila SMN homolog. We identified more than 300 candidate genes that alter an Smn-dependent phenotype in vivo. Integrating the results from our genetic screens, large-scale protein interaction studies, and bioinformatic analysis, we define a unique interactome for SMN that provides a knowledge base for a better understanding of SMA.Stem Cell and Regenerative Biolog

Plasmodium falciparum-Infected Erythrocytes Induce Granzyme B by NK Cells through Expression of Host-Hsp70

In the early immune response to Plasmodium falciparum-infected erythrocytes (iRBC), Natural Killer (NK) cells are activated, which suggests an important role in innate anti-parasitic immunity. However, it is not well understood whether NK cells directly recognize iRBC or whether stimulation of NK cells depends mainly on activating signals from accessory cells through cell-to-cell contact or soluble factors. In the present study, we investigated the influence of membrane-bound host Heat shock protein (Hsp) 70 in triggering cytotoxicity of NK cells from malaria-naïve donors or the cell line NK92 against iRBC. Hsp70 and HLA-E membrane expression on iRBC and potential activatory NK cell receptors (NKG2C, CD94) were assessed by flow cytometry and immunoblot. Upon contact with iRBC, Granzyme B (GzmB) production and release was initiated by unstimulated and Hsp70-peptide (TKD) pre-stimulated NK cells, as determined by Western blot, RT-PCR and ELISPOT analysis. Eryptosis of iRBC was determined by Annexin V-staining. Our results suggest that presence of Hsp70 and absence of HLA-E on the membrane of iRBC prompt the infected host cells to become targets for NK cell-mediated cytotoxicity, as evidenced by impaired parasite development. Contact of iRBC with NK cells induced release of GzmB. We propose that following GzmB uptake, iRBC undergo eryptosis via a perforin-independent, GzmB-mediated mechanism. Since NK activity toward iRBC could be specifically enhanced by TKD peptide and abrogated to baseline levels by blocking Hsp70 exposure, we propose TKD as an innovative immunostimulatory agent to be tested as an adjunct to anti-parasitic treatments in vivo

Limited response of NK92 cells to Plasmodium falciparum-infected erythrocytes

<p>Abstract</p> <p>Background</p> <p>Mechanisms by which anti-malarial immune responses occur are still not fully clear. Natural killer (NK) cells are thought to play a pivotal role in innate responses against <it>Plasmodium falciparum</it>. In this study, the suitability of NK92 cells as models for the NK mechanisms involved in the immune response against malaria was investigated.</p> <p>Methods</p> <p>NK92 cells were assessed for several signs of activation and cytotoxicity due to contact to parasites and were as well examined by oligonucleotide microarrays for an insight on the impact <it>P. falciparum</it>-infected erythrocytes have on their transcriptome. To address the parasite side of such interaction, growth inhibition assays were performed including non-NK cells as controls.</p> <p>Results</p> <p>By performing microarrays with NK92 cells, the impact of parasites on a transcriptional level was observed. The findings show that, although not evidently activated by iRBCs, NK92 cells show transcriptional signs of priming and proliferation. In addition, decreased parasitaemia was observed due to co-incubation with NK92 cells. However, such effect might not be NK-specific since irrelevant cells also affected parasite growth <it>in vitro</it>.</p> <p>Conclusions</p> <p>Although NK92 cells are here shown to behave as poor models for the NK immune response against parasites, the results obtained in this study may be of use for future investigations regarding host-parasites interactions in malaria.</p

Characterisation of the Trichinella spiralis deubiquitinating enzyme, TsUCH37, an evolutionarily conserved proteasome interaction partner.

Trichinella spiralis is a parasitic nematode that infects mammals indiscriminately. Although the biggest impact of trichinellosis is observed in developing countries, the parasite is found on all continents except Antarctica. In humans, Trichinella infection contributes globally to helminth related morbidity and disability adjusted life years. In animals, infection is implicated as a serious agricultural problem and drug treatment is largely ineffective. During chronic infection, larvae invade skeletal muscle cells, forming a nurse cell complex in which they become encysted. The nurse cell is a product of the severe disruption of the host cell homeostasis. Proteins of the Ub/proteasome pathway are highly conserved throughout evolution, and considering their importance in the regulation of cell homeostasis, provide interesting and novel therapeutic targets for various diseases. In order to target this system in parasites, pathogen proteins that play a role in this pathway must be identified. We report the identification of the first T. spiralis deubiquitinating enzyme, and show evidence that the function of this protein as a proteasome interaction partner has been evolutionarily conserved. We show that members of this enzyme family are important for T. spiralis survival and that the use of inhibitor compounds may help elucidate their role in infection

Flow-induced delayed Freedericksz transition

We demonstrate that a compact manometer experiment allows direct observation of a delay to the classical electric-field-induced Freedericksz transition produced by flow in a highly dispersive nematic liquid crystal layer. The Ericksen-Leslie equations are used to show that a flow aligning torque generated in the nematic layer under Poiseuille flow competes with the orthogonal electric-field reorientation torque. This model fully reproduces the experimental results using only self-consistently determined viscosity values, and predicts a more generally applicable expression for the dependence of the delay Ec∝√ζ/Δχe on the shear rate ζ and on the electric susceptibility anisotropy Δχe