Fibrinogen-mimicking, multiarm nanovesicles for human thrombus-specific delivery of tissue plasminogen activator and targeted thrombolytic therapy

Clinical use of tissue plasminogen activator (tPA) in thrombolytic therapy is limited by its short circulation time and hemorrhagic side effects. Inspired by fibrinogen binding to activated platelets, we report a fibrinogen-mimicking, multiarm nanovesicle for thrombus-specific tPA delivery and targeted thrombolysis. This biomimetic system is based on the lipid nanovesicle coated with polyethylene glycol (PEG) terminally conjugated with a cyclic RGD (cRGD) peptide. Our experiments with human blood demonstrated its highly selective binding to activated platelets and efficient tPA release at a thrombus site under both static and physiological flow conditions. Its clot dissolution time in a microfluidic system was comparable to that of free tPA. Furthermore, we report a purpose-built computational model capable of simulating targeted thrombolysis of the tPA-loaded nanovesicle and with a potential in predicting the dynamics of thrombolysis in physiologically realistic scenarios. This combined experimental and computational work presents a promising platform for development of thrombolytic nanomedicines

Heavily electron-doped electronic structure and isotropic superconducting gap in AxFe2Se2 (A=K,Cs)

The low energy band structure and Fermi surface of the newly discovered superconductor, AxFe2Se2 (A=K,Cs), have been studied by angle-resolved photoemission spectroscopy. Compared with iron pnictide superconductors, AxFe2Se2 (A=K,Cs) is the most heavily electron-doped with Tc~30 K. Only electron pockets are observed with an almost isotropic superconducting gap of ~10.3 meV, while there is no hole Fermi surface near the zone center, which indicates the inter-pocket hopping or Fermi surface nesting is not a necessary ingredient for the unconventional superconductivity in iron-based superconductors. Thus, the sign changed s$_\pm$ pairing symmetry, a leading candidate proposed for iron-based superconductors, becomes conceptually irrelevant in describing the superconducting state here. A more conventional s-wave pairing is a better description.Comment: 4 pages, 4 figures, published online in Nature Materials 201

Protection of Human Lung Cells against Hyperoxia Using the DNA Base Excision Repair Genes hOgg1 and Fpg

Hyperoxia causes pulmonary toxicity in part by injuring alveolar epithelial cells. Previous studies have shown that toxic oxygen-derived species damage DNA and this damage is recognized and repaired by either human enzyme 8-oxoguanine DNA glycosylase (hOgg1) or Escherichia coli enzyme formamidopyrimidine DNA glycosylase (Fpg). To determine whether these DNA repair proteins can reduce O2-mediated DNA damage in lung cells, A549 lung epithelial cells were transduced with either hOgg1 or Fpg using a retroviral vector containing enhanced green fluorescent protein. Expression of each gene in the transduced cells was confirmed by fluorescent microscopy, Northern blotting, Western blotting, and an enzymatic oligonucleotide cleavage assay. A549 cells expressing either hOgg1 or Fpg were protected from hyperoxia as evidenced by a decrease in DNA damage and a corresponding increase in cell survival. Further, we determined that overexpression of hOgg1 or Fpg partially mitigated the toxic effects of hydrogen peroxide in lung cells. Our data suggest that increased expression of DNA base excision repair genes might represent a new approach for protecting critical lung cells from the toxic effects of hyperoxia

The MAJORANA DEMONSTRATOR: A Search for Neutrinoless Double-beta Decay of Germanium-76

The {\sc Majorana} collaboration is searching for neutrinoless double beta decay using $^{76}$Ge, which has been shown to have a number of advantages in terms of sensitivities and backgrounds. The observation of neutrinoless double-beta decay would show that lepton number is violated and that neutrinos are Majorana particles and would simultaneously provide information on neutrino mass. Attaining sensitivities for neutrino masses in the inverted hierarchy region, $15 - 50$ meV, will require large, tonne-scale detectors with extremely low backgrounds, at the level of $\sim$1 count/t-y or lower in the region of the signal. The {\sc Majorana} collaboration, with funding support from DOE Office of Nuclear Physics and NSF Particle Astrophysics, is constructing the {\sc Demonstrator}, an array consisting of 40 kg of p-type point-contact high-purity germanium (HPGe) detectors, of which $\sim$30 kg will be enriched to 87% in $^{76}$Ge. The {\sc Demonstrator} is being constructed in a clean room laboratory facility at the 4850' level (4300 m.w.e.) of the Sanford Underground Research Facility (SURF) in Lead, SD. It utilizes a compact graded shield approach with the inner portion consisting of ultra-clean Cu that is being electroformed and machined underground. The primary aim of the {\sc Demonstrator} is to show the feasibility of a future tonne-scale measurement in terms of backgrounds and scalability.Comment: Proceedings for the MEDEX 2013 Conferenc

Final results for the neutron β-asymmetry parameter A₀ from the UCNA experiment

The UCNA experiment was designed to measure the neutron β-asymmetry parameter A0 using polarized ultracold neutrons (UCN). UCN produced via downscattering in solid deuterium were polarized via transport through a 7 T magnetic field, and then directed to a 1 T solenoidal electron spectrometer, where the decay electrons were detected in electron detector packages located on the two ends of the spectrometer. A value for A0 was then extracted from the asymmetry in the numbers of counts in the two detector packages. We summarize all of the results from the UCNA experiment, obtained during run periods in 2007, 2008–2009, 2010, and 2011–2013, which ultimately culminated in a 0.67% precision result for A₀

Status of the MAJORANA DEMONSTRATOR experiment

The MAJORANA DEMONSTRATOR neutrinoless double beta-decay experiment is currently under construction at the Sanford Underground Research Facility in South Dakota, USA. An overview and status of the experiment are given.Comment: 8 pages, proceeding from VII International Conference on Interconnections between Particle Physics and Cosmology (PPC 2013), submitted to AIP proceeding