Plasmonic Approaches and Photoemission: Ag-Based Photocathodes

Photocathodes play an important role in present large accelerator facilities by providing polarized or un-polarized electron beams. Current state-of-art high polarization photocathodes consist of strained super-lattice GaAs based photocathodes, e.g. GaAs/GaAsP has a quantum efficiency ~1% and polarization ~90% at near-infrared wavelength for the incident light. Despite the advantages offered by metallic photocathodes regarding longer life time, fast response time and low requirements of ultra-high vacuum environment, they have not been put to use due to their low quantum efficiency, even though one can envision several approaches to achieve spin-polarization from them. A possible solution is to apply the Fano resonance, that involves coupling the surface plasmon resonance and the 1st diffraction order of incident light on a corrugated silver surface. This thesis demonstrates that this approach yields an enhancement of the QE performance of a cesiated silver grating cathode for light incident at the resonance angle, compared to that of a cesiated flat silver cathode measured in the same system. By altering the grating profile through oblique angle deposition (OAD) of a silver thin film onto a grating surface using magnetron sputtering deposition, one can further enhance the Fano resonance and consequently improve the electric field intensity near the silver cathode surface. QE measurements confirm an enhancement of QE (26%) on the cesiated OAD sample compared to a cesiated one obtained under normal deposition(ND) for light incident at resonance, respectively, showcasing a possible road for metallic photocathodes for this application

Tailored Fano resonance and localized electromagnetic field enhancement in Ag gratings

Metallic gratings can support Fano resonances when illuminated with EM radiation, and their characteristic reflectivity versus incident angle lineshape can be greatly affected by the surrounding dielectric environment and the grating geometry. By using conformal oblique incidence thin film deposition onto an optical grating substrate, it is possible to increase the grating amplitude due to shadowing effects, thereby enabling tailoring of the damping processes and electromagnetic field couplings of the Fano resonances, hence optimizing the associated localized electric field intensity. To investigate these effects we compare the optical reflectivity under resonance excitation in samples prepared by oblique angle deposition (OAD) and under normal deposition (ND) onto the same patterned surfaces. We observe that by applying OAD method, the sample exhibits a deeper and narrower reflectivity dip at resonance than that obtained under ND. This can be explained in terms of a lower damping of Fano resonance on obliquely deposited sample and leads to a stronger localized electric field. This approach opens a fabrication path for applications where tailoring the electromagnetic field induced by Fano resonance can improve the figure of merit of specific device characteristics, e.g. quantum efficiency (QE) in grating-based metallic photocathodes

Abl Family Tyrosine Kinases Are Essential for Basement Membrane Integrity and Cortical Lamination in the Cerebellum

The Abl family nonreceptor tyrosine kinases, consisting of closely related Abl and Arg (Abl-related gene), play essential roles in mouse neurulation, but their functions in the subsequent development of CNS are poorly understood. Here, we show that conditional deletion of Abl in precursors of neurons and glia on an Arg knock-out background leads to striking cerebellar malformations, including defects in anterior cerebellar morphogenesis, granule cell ectopia, and hypoplasia. Time course analyses reveal that the abnormal anterior cerebellar foliation results from local disruptions of the basement membrane (BM) located between radial glial endfeet and the meninges during embryonic cerebellar development. Granule cell ectopia and hypoplasia are also associated with the breaches in the BM and abnormal Bergmann glial networks during postnatal cerebellar development. In vitro culture experiments indicate that Abl/Arg-deficient granule cells can interact with glial processes and proliferate normally in response to sonic hedgehog compared to cells isolated from control mice. Consistent with these findings, selective ablation of Abl family kinases in cerebellar granule cells alone does not cause any abnormality, suggesting that deletion of Abl/Arg from glia is likely required for the mutant phenotype. Together, these results provide compelling evidence that Abl and Arg play key redundant roles in BM maintenance and cortical lamination in the cerebellum

Binding Quantum Dots to Silk Biomaterials for Optical Sensing

Quantum dots (QDs), have great potential for fabricating optical sensing devices and imaging biomaterial degradation in vivo. In the present study, 2-mercaptoethylamine- (MEA-) and mercaptopropionic acid- (MPA-) capped CdTe-QDs were physically incorporated in silk films that contained a high content (>30%) of crystalline beta-sheet structure. The beta-sheets were induced by the addition of glycerol, water annealing, glycerol/annealing, or treatment with methanol. Incorporation of QDs did not influence the formation of beta-sheets. When the films were extracted with water, most QDs remained associated with the silk, based on the retention of photoluminescence in the silk films and negligible photoluminescence in the extracts. Compared to the solution state, photoluminescence intensity significantly decreased for MEA-QDs but not for MPA-QDs in the silk films, while the emission maximum blue shifted (≈4 nm) slightly for both. Further film digestion using protease XIV, alpha-chymotrypsin, and the combination of the two proteases suggested that QDs may be bound to the silk beta-sheet regions but not the amorphous regions. QDs photoluminescence in silk films was quenched when the concentration of hydrogen peroxide (H2O2) was above 0.2-0.3 mM, indicating the QDs-incorporated silk films can be used to report oxidation potential in solution

Functional characterization of PETIOLULE-LIKE PULVINUS (PLP) gene in abscission zone development in Medicago truncatula and its application to genetic improvement of alfalfa

Alfalfa (Medicago sativa L.) is one of the most important forage crops throughout the world. Maximizing leaf retention during the haymaking process is critical for achieving superior hay quality and maintaining biomass yield. Leaf abscission process affects leaf retention. Previous studies have largely focused on the molecular mechanisms of floral organ, pedicel and seed abscission but scarcely touched on leaf and petiole abscission. This study focuses on leaf and petiole abscission in the model legume Medicago truncatula and its closely related commercial species alfalfa. By analysing the petiolule-like pulvinus (plp) mutant in M. truncatula at phenotypic level (breakstrength and shaking assays), microscopic level (scanning electron microscopy and cross-sectional analyses) and molecular level (expression level and expression pattern analyses), we discovered that the loss of function of PLP leads to an absence of abscission zone (AZ) formation and PLP plays an important role in leaflet and petiole AZ differentiation. Microarray analysis indicated that PLP affects abscission process through modulating genes involved in hormonal homeostasis, cell wall remodelling and degradation. Detailed analyses led us to propose a functional model of PLP in regulating leaflet and petiole abscission. Furthermore, we cloned the PLP gene (MsPLP) from alfalfa and produced RNAi transgenic alfalfa plants to down-regulate the endogenous MsPLP. Down-regulation of MsPLP results in altered pulvinus structure with increased leaflet breakstrength, thus offering a new approach to decrease leaf loss during alfalfa haymaking process

Potential Mechanisms of the Impact of Hepatocyte Growth Factor Gene-Modified Tendon Stem Cells on Tendon Healing

The therapeutic impact of stem cells is potentially largely attributable to secretion of exosomes and soluble factors. The present study evaluates the impact of hepatocyte growth factor (HGF)–expressing tendon stem cells (TSCs) on tendon healing in a rat model. Patellar tendon TSCs were isolated and underwent transfection with lentiviral vectors containing HGF or green fluorescent protein (GFP) genes. In vivo, immunohistochemistry of tendons sampled 1 week postsurgery demonstrated that all stem cell–treated groups exhibited higher numbers of CD163+ M2 monocytes and IL-10+ cells (anti-inflammatory), and lower numbers of CCR7+ M1 monocytes and IL-6+ as well as COX-2+ cells (pro-inflammatory). Effects were most pronounced in the HGF-expressing TSCs (TSCs + HGF) treated group. Histology ± immunohistochemistry of tendons sampled 4 and 8 weeks postsurgery demonstrated that all stem cell–treated groups exhibited more ordered collagen fiber arrangement and lower levels of COLIII, α-SMA, TGF-β1, and fibronectin (proteins relevant to fibroscarring). Effects were most pronounced in the TSCs + HGF–treated group. For the in vitro study, isolated tendon fibroblasts pretreated with TGF-β1 to mimic the in vivo microenvironment of tendon injury were indirectly cocultured with TSCs, TSCs + GFP, or TSCs + HGF using a transwell system. Western blotting demonstrated that all stem cell types decreased TGF-β1-induced increases in fibroblast levels of COX-2, COLIII, and α-SMA, concomitant with decreased activation of major TGF-β1 signaling pathways (p38 MAPK, ERK1/2, but not Smad2/3). This effect was most pronounced for TSCs + HGF, which also decreased the TGF-β1-induced increase in activation of the Smad2/3 signaling pathway. The presence of specific inhibitors of these pathways during fibroblast TGF-β1 stimulation also attenuated increases in levels of COX-2, COLIII, and α-SMA. In conclusion, TSCs + HGF, which exhibit HGF overexpression, may promoting tendon healing via decreasing inflammation and fibrosis, perhaps partly via inhibiting TGF-β1-induced signaling. These findings identify a novel potential therapeutic strategy for tendon injuries, warranting additional research

Dissociation of EphB2 Signaling Pathways Mediating Progenitor Cell Proliferation and Tumor Suppression

SummarySignaling proteins driving the proliferation of stem and progenitor cells are often encoded by proto-oncogenes. EphB receptors represent a rare exception; they promote cell proliferation in the intestinal epithelium and function as tumor suppressors by controlling cell migration and inhibiting invasive growth. We show that cell migration and proliferation are controlled independently by the receptor EphB2. EphB2 regulated cell positioning is kinase-independent and mediated via phosphatidylinositol 3-kinase, whereas EphB2 tyrosine kinase activity regulates cell proliferation through an Abl-cyclin D1 pathway. Cyclin D1 regulation becomes uncoupled from EphB signaling during the progression from adenoma to colon carcinoma in humans, allowing continued proliferation with invasive growth. The dissociation of EphB2 signaling pathways enables the selective inhibition of the mitogenic effect without affecting the tumor suppressor function and identifies a pharmacological strategy to suppress adenoma growth

Validation of Drug Like Inhibitors for the New Proton Activated Chloride Channel

PAC, proton-activated chloride channel, is an evolutionarily conserved membrane channel that is activated by extracellular acidification. The molecular identity of PAC is recently cloned, opening the door for further investigations on the channel. Emerging evidence showed that PAC was involved in acid induced cell death, and that mice without the PAC channel showed better recovery after an ischemic stroke model. Yet, pharmacological tools that specifically inhibit PAC are lacking. To overcome this limitation and potentially provide treatment for acidosis related diseases, a high-throughput screening was performed and more than 2000 FDA (Food and Drug Administration) proved drugs were screened and repurposed as potential inhibitors of PAC. During this experiment, the top three drugs found in the screening, Resveratrol, Neostigmine Bromide and 3-Formyl Rifamycin were tested as PAC inhibitors. It has been hypothesized that those three drugs should inhibit acidic induced PAC current. Whole-cell patch clamp experiment was conducted in HEK293 cells to confirm their inhibition on PAC. HEK293 cells were perfused with acidic solution to evoke PAC, and inhibitors were applied together with acidic solution after PAC reached complete opening. The reduction of currents were recorded and compared after the application of inhibitors. 20uM Resveratrol showed 32% inhibition on PAC, while 20uM Neostigmine Bromide showed 50% inhibition and 20uM 3-Formyl Rifamycin showed 52% inhibition when perfusing with pH=4.6 solutions. Our studies suggest that all three drugs showed significant inhibition of PAC channel activity, providing promising pharmacological means to manipulate PAC in vivo

Piezo1, a mechanically activated ion channel, is required for vascular development in mice

Mechanosensation is perhaps the last sensory modality not understood at the molecular level. Ion channels that sense mechanical force are postulated to play critical roles in a variety of biological processes including sensing touch/pain (somatosensation), sound (hearing), and shear stress (cardiovascular physiology); however, the identity of these ion channels has remained elusive. We previously identified Piezo1 and Piezo2 as mechanically activated cation channels that are expressed in many mechanosensitive cell types. Here, we show that Piezo1 is expressed in endothelial cells of developing blood vessels in mice. Piezo1-deficient embryos die at midgestation with defects in vascular remodeling, a process critically influenced by blood flow. We demonstrate that Piezo1 is activated by shear stress, the major type of mechanical force experienced by endothelial cells in response to blood flow. Furthermore, loss of Piezo1 in endothelial cells leads to deficits in stress fiber and cellular orientation in response to shear stress, linking Piezo1 mechanotransduction to regulation of cell morphology. These findings highlight an essential role of mammalian Piezo1 in vascular development during embryonic development