Publications

Two entangled 2D square covalent organic frameworks (COFs) have been synthesized from 4,4',4″,4‴-(9,9'-spirobi[fluorene]-2,2',7,7'-tetrayl)-tetrabenzaldehhyde (SFTB) and <i>p</i>-phenylenediamine (PPA) and benzidine (BZD) to form COF-38, [(SFTB)(PPA)₂]_imine, and its isoreticular form COF-39, [(SFTB)(BZD)₂]_imine. We also report the single-crystal electron diffraction structure of COF-39 and find that it is composed of mutually entangled 2D square nets (<b>sql</b>). These COFs represent the first examples of entangled 2D COF structures, which, as we illustrate, were made possible by our strategy of using the distorted tetrahedral SFTB building unit. SFTB overcomes the propensity of 2D COFs to stack through π-π stacking and allows entanglements to form. This work significantly adds to the design principles of COFs.

Abstract In allogeneic hematopoietic stem cell transplantation (HSCT), identification of mechanisms to control GVHD yet maintain GVL responses is of critical importance. One key effector cell that mediates both GVHD and GVL is the CD8+ T cell, which expands in response to T cell receptor (TCR) stimulation by allogeneic MHC class I molecules during allogeneic HSCT. In addition, co-stimulatory molecules facilitate the TCR-mediated activation process and the effector function of CD8+ T cells. Recent data suggest that NKG2D may play a co-stimulatory role in activation and in augmenting anti-tumor cytotoxic responses of CD8+ T cells. NKG2D is an NK cell-associated receptor that is also expressed on all human CD8+ T cells and on activated/memory mouse CD8+ T cells. NKG2D recognizes a diverse array of MHC-related ligands that are expressed by many tumors and induced on cells under stress such as myeloablative conditioning during HSCT. As the role of NKG2D in allogeneic HSCT is unknown, we hereby investigated the role of NKG2D on CD8+ T cells in a mouse model of GVHD and GVL. Our results show that a large fraction (40-50%) of mouse CD8+ T cells inducibly express NKG2D upon activation by allogeneic MHC in vitro and in vivo. To test the role of NKG2D in GVHD pathogenesis, we employed a major MHC-mismatched mouse model of GVHD involving the transplantation of C57BL/6-derived CD8+ T cells and bone marrow (BM) into lethally irradiated Balb/c mice (B6→Balb/c). Using 3 different approaches to block NKG2D on CD8+ T cells (shRNA-mediated silencing, germline NKG2D deficiency, and antibody blockade), we found that weight loss, clinical score, and survival were significantly improved in transplanted mice with NKG2D blockade. The attenuation in GVHD correlated with a significant reduction in TNFα and IFNγ production, cytotoxicity, and proliferation (BrdU incorporation) by CD8+ T cells. Although CD4+ T cells did not express NKG2D, a protective effect of NKG2D blockade was still observed in GVHD induced by a mixture of CD8+ and CD4+ T cells, albeit to a lesser extent. We next tested the effects of NKG2D on CD8+ T cell-mediated GVL. To this end, irradiated Balb/c mice were transplanted with C57BL/6-derived CD8+ T cells and BM, challenged intravenously with luciferase-positive A20 leukemia cells, and followed by total body imaging of luciferase-expressing cells. Given that NKG2D ligands are constitutively expressed on many tumor cells and plays an important role in their eradication, we predicted that continuous NKG2D blockade would inhibit GVL effects. However, as NKGD ligands are upregulated only transiently on stressed normal tissue, we reasoned that transient NKG2D blockade might be sufficient to attenuate GVHD and allow CD8+ T cells to regain their GVL function. To test this hypothesis, we compared the effect of anti-NKG2D antibody as continuous treatment or as 5-day transient treatment to mice receiving isotype control antibody. As expected, mice that received isotype control antibody cleared the A20 cells but developed severe GVHD. Continuous anti-NKG2D antibody-mediated blockade improved GVHD but also blunted the GVL response leading to increased A20 growth. In contrast, a large proportion of mice transiently treated with anti-NKG2D antibody cleared the A20 cells, while maintaining the attenuated GVHD state. Together, these data support a positive role of NKG2D on CD8+ T cells in mediating GVHD and GVL. Given the transient nature of NKG2D ligand upregulation on stressed tissues, a window of opportunity may exist where transient NKG2D blockade could provide a novel therapeutic strategy for treatment of acute GVHD while preserving the GVL function of CD8+ T cells after allogeneic HSCT. Disclosures: No relevant conflicts of interest to declare.

view Abstract Citations (133) References (59) Co-Reads Similar Papers Volume Content Graphics Metrics Export Citation NASA/ADS Hubble Space Telescope Ultraviolet Imaging and Spectroscopy of the Bright Starburst in the Wolf-Rayet Galaxy NGC 4214 Leitherer, Claus ; Vacca, William D. ; Conti, Peter S. ; Filippenko, Alexei V. ; Robert, Carmelle ; Sargent, Wallace L. W. Abstract We have obtained an HST Faint Object Camera ultraviolet image and Faint Object Spectrograph ultraviolet spectra of the central starburst region in the nearby amorphous galaxy NGC 4214. The ultraviolet image reveals a bright, compact, starburst knot surrounded by more than 200 fainter pointlike sources. Spectral synthesis modeling of the ultraviolet spectrum of the central starburst knot suggests the stellar population has an age of 4-5 Myr. The extinction-corrected ultraviolet flux implies that hundreds of 0-type stars are contained within a diameter of at most 5 pc. The inferred number of Wolf-Rayet (W-R) stars implies that the star formation episode occurred in a short duration burst. The starburst knot contains roughly twice the number of O stars as in a similar size region centered on R136a in 30 Doradus, but it is slightly older. The knot in NGC 4214 is comparable in size and luminosity to the starburst knots identified in the core of the W-R galaxy He 2-10 and to the super star clusters found in other star-forming galaxies. The number of Lyman continuum photons inferred from Hα measurements is at least a factor of 4 smaller than that predicted from the observed numbers of hot stars; this starburst knot is thus "density bounded" to ionizing radiation. The fainter pointlike sources seen in the ultraviolet image are probably individual hot stars or small groups of stars. The ultraviolet luminosity function of these objects is similar to that found for stars within 30 Doradus. Publication: The Astrophysical Journal Pub Date: July 1996 DOI: 10.1086/177456 Bibcode: 1996ApJ...465..717L Keywords: GALAXIES: INDIVIDUAL NGC NUMBER: NGC 4214; GALAXIES: STARBURST; GALAXIES: STELLAR CONTENT; ULTRAVIOLET: GALAXIES full text sources ADS | data products SIMBAD (7) NED (1) MAST (1) ESA (1)

Supported metal nanoparticles have been fabricated using electron beam lithography (EBL) and pulsed laser deposition (PLD). EBL produced ordered two-dimensional arrays with particle diameters of 40 ± 0.5 nm, uniform interparticle distances (230 ± 2 nm), and uniform height (20 ± 0.5 nm). Due to the narrow size distribution of the particles and the long-range (cm2) order, the arrays produced using EBL were applied as models for supported metal catalysts. Smaller particle sizes can be obtained using PLD, but with larger size and spatial distributions of the particles. Particles fabricated with PLD have mean sizes ranging from 2 to 50 nm, depending on the ambient pressure during deposition. The nanoparticles have been characterized using TEM, AFM, UPS, and SEM. Reaction studies of ethylene hydrogenation on Pt nanoparticle arrays have demonstrated that detectable amounts of ethane are produced, despite the low surface area of the model catalysts.