Microstructure of 5 keV gold-implanted polydimethylsiloxane

The first high-resolution transmission electron microscopy (TEM) cross-section images of flexible electrodes fabricated by gold ion implantation at 5 keV into polydimethylsiloxane (PDMS) are presented. A TEM sample preparation method based on cryoultramicrotomy, adapted for extremely low-modulus (1 MPa) elastomers, was developed, allowing the gold nanoparticles in a PDMS matrix to be imaged. The cluster size, size distribution and implantation depth of 50 nm were determined from the images and used to calculate the Young’s modulus of the implanted layer

Spores of Clostridium engineered for clinical efficacy and safety cause regression and cure of tumors in vivo

Spores of some species of the strictly anaerobic bacteria Clostridium naturally target and partially lyse the hypoxic cores of tumors, which tend to be refractory to conventional therapies. The anti-tumor effect can be augmented by engineering strains to convert a non-toxic prodrug into a cytotoxic drug specifically at the tumor site by expressing a prodrug-converting enzyme (PCE). Safe doses of the favored prodrug CB1954 lead to peak concentrations of 6.3 µM in patient sera, but at these concentration(s) known nitroreductase (NTR) PCEs for this prodrug show low activity. Furthermore, efficacious and safe Clostridium strains that stably express a PCE have not been reported. Here we identify a novel nitroreductase from Neisseria meningitidis, NmeNTR, which is able to activate CB1954 at clinically-achievable serum concentrations. An NmeNTR expression cassette, which does not contain an antibiotic resistance marker, was stably localized to the chromosome of Clostridium sporogenes using a new integration method, and the strain was disabled for safety and containment by making it a uracil auxotroph. The efficacy of Clostridium-Directed Enzyme Prodrug Therapy (CDEPT) using this system was demonstrated in a mouse xenograft model of human colon carcinoma. Substantial tumor suppression was achieved, and several animals were cured. These encouraging data suggest that the novel enzyme and strain engineering approach represent a promising platform for the clinical development of CDEPT.status: publishe

Rationale and design of the Cyclosporine to ImpRove Clinical oUtcome in ST-elevation myocardial infarction patients (the CIRCUS trial)

Abstract: Background Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. Methods CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow <= 1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1: 1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in theminutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction. Results Recruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015. Conclusions The CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up

PILOT: measuring the FIR astrophysical dust emission

Measuring precisely the faint polarization of the Far-Infrared and sub-millimetre sky is the next observational challenge of modern astronomy. In particular, detection the B-mode polarization from the Cosmic Microwave Background (CMB) shall reveal the inflationary periods in the very early universe. Such measurements will require very high sensitivity and very low instrumental systematic effects. As for measurements of the CMB intensity, sensitive measurements of the CMB polarization will be made difficult by the presence of foreground emission from our own Milky Way, which is orders of magnitude higher than the faint polarized cosmological signal. Such foreground emission will have to be understood very accurately and removed from cosmological measurements. This polarized emission is also interesting in itself, since it brings information relevant to star formation processes, about the orientation of the magnetic field in our Galaxy through the alignment of dust grains. I will first summarize our current knowledge in this field. I will then describe the PILOT balloon-borne experiment project, which is dedicated to measuring precisely the polarization of faint diffuse dust emission in the Far-Infrared in our Galaxy