In vivo imaging of pyrrole-imidazole polyamides with positron emission tomography

The biodistribution profiles in mice of two pyrrole-imidazole polyamides were determined by PET. Pyrrole-imidazole polyamides are a class of small molecules that can be programmed to bind a broad repertoire of DNA sequences, disrupt transcription factor-DNA interfaces, and modulate gene expression pathways in cell culture experiments. The 18F-radiolabeled polyamides were prepared by oxime ligation between 4-[18F]-fluorobenzaldehyde and a hydroxylamine moiety at the polyamide C terminus. Small animal PET imaging of radiolabeled polyamides administered to mice revealed distinct differences in the biodistribution of a 5-ring β-linked polyamide versus an 8-ring hairpin, which exhibited better overall bioavailability. In vivo imaging of pyrrole-imidazole polyamides by PET is a minimum first step toward the translation of polyamide-based gene regulation from cell culture to small animal studies

Innate Immunity in Human Embryonic Stem Cells: Comparison with Adult Human Endothelial Cells

Treatment of human disease with human embryonic stem cell (hESC)-derived cells is now close to reality, but little is known of their responses to physiological and pathological insult. The ability of cells to respond via activation of Toll like receptors (TLR) is critical in innate immune sensing in most tissues, but also extends to more general danger sensing, e.g. of oxidative stress, in cardiomyocytes. We used biomarker release and gene-array analysis to compare responses in hESC before and after differentiation, and to those in primary human endothelial cells. The presence of cardiomyocytes and endothelial cells was confirmed in differentiated cultures by immunostaining, FACS-sorting and, for cardiomyocytes, beating activity. Undifferentiated hESC did not respond with CXCL8 release to Gram positive or Gram negative bacteria, or a range of PAMPs (pathogen associated molecular patterns) for TLRs 1-9 (apart from flagellin, an activator of TLR5). Surprisingly, lack of TLR-dependent responses was maintained over 4 months of differentiation of hESC, in cultures which included cardiomyocytes and endothelial cells. In contrast, primary cultures of human aortic endothelial cells (HAEC) demonstrated responses to a broad range of PAMPs. Expression of downstream TLR signalling pathways was demonstrated in hESC, and IL-1β, TNFα and INFγ, which bypass the TLRs, stimulated CXCL8 release. NFκB pathway expression was also present in hESC and NFκB was able to translocate to the nucleus. Low expression levels of TLRs were detected in hESC, especially TLRs 1 and 4, explaining the lack of response of hESC to the main TLR signals. TLR5 levels were similar between differentiated hESC and HAEC, and siRNA knockdown of TLR5 abolished the response to flagellin. These findings have potential implications for survival and function of grafted hESC-derived cells

Fundamentals of interface phenomena in advanced bulk nanoscale materials

The review is devoted to a study of interface phenomena influencing advanced properties of nanoscale materials processed by means of severe plastic deformation, high-energy ball milling and their combinations. Interface phenomena include processes of interface defect structure relaxation from a highly nonequilibrium state to an equilibrium condition, grain boundary phase transformations and enhanced grain boundary and triple junction diffusivity. On the basis of an experimental investigation, a theoretical description of the key interfacial phenomena controlling the functional properties of advanced bulk nanoscale materials has been conducted. An interface defect structure investigation has been performed by TEM, high-resolution x-ray diffraction, atomic simulation and modeling. The problem of a transition from highly non-equilibrium state to an equilibrium one, which seems to be responsible for low thermostability of nanoscale materials, was studied. Also enhanced grain boundary diffusivity is addressed. Structure recovery and dislocation emission from grain boundaries in nanocrystalline materials have been investigated by analytical methods and modeling

Effects of Extra Dimensions on Unitarity and Higgs Boson Mass

We study the unitarity constraint on the two body Higgs boson elastic scattering in the presence of extra dimensions. The contributions from exchange of spin-2 and spin-0 Kaluza-Klein states can have large effect on the partial wave amplitude. Unitarity condition restrict the maximal allowed value for the ratio $r$ of the center of mass energy to the gravity scale to be less than one. Although the constraint on the standard Higgs boson mass for $r$ of order one is considerably relaxed, for small $r$ the constraint is similar to that in the Standard Model. The resulting bound on the Higgs boson mass is not dramatically altered if perturbative calculations are required to be valid up to the maximal allowed value for $r$.Comment: References added, RevTex, 9 pages with two figure

The Al-Rich Part of the Fe-Al Phase Diagram

The Al-rich part of the Fe-Al phase diagram between 50 and 80 at.% Al including the complex intermetallic phases Fe$_{5}$Al$_{8}$ (ε), FeAl$_{2}$, Fe$_{2}$Al$_{5}$, and Fe4Al$_{13}$ was re-investigated in detail. A series of 19 alloys was produced and heat-treated at temperatures in the range from 600 to 1100 °C for up to 5000 h. The obtained data were further complemented by results from a number of diffusion couples, which helped to determine the homogeneity ranges of the phases FeAl$_{2}$, Fe$_{2}$Al$_{5}$, and Fe$_{4}$Al$_{13}$. All microstructures were inspected by scanning electron microscopy (SEM), and chemical compositions of the equilibrium phases as well as of the alloys were obtained by electron probe microanalysis (EPMA). Crystal structures and the variation of the lattice parameters were studied by x-ray diffraction (XRD) and differential thermal analysis (DTA) was applied to measure all types of transition temperatures. From these results, a revised version of the Al-rich part of the phase diagram was constructed

Search for electron antineutrino interactions with the Borexino Counting Test Facility at Gran Sasso

Electron antineutrino interactions above the inverse beta decay energy of protons (E_\bar{\nu}_e>1.8) where looked for with the Borexino Counting Test Facility (CTF). One candidate event survived after rejection of background, which included muon-induced neutrons and random coincidences. An upper limit on the solar $\bar{\nu}_{e}$ flux, assumed having the $^8$B solar neutrino energy spectrum, of 1.1$\times10^{5}$ cm$^{-2}$~s$^{-1}$ (90% C.L.) was set with a 7.8 ton $\times$ year exposure. This upper limit corresponds to a solar neutrino transition probability, $\nu_{e} \to \bar{\nu}_{e}$, of 0.02 (90% C.L.). Predictions for antineutrino detection with Borexino, including geoneutrinos, are discussed on the basis of background measurements performed with the CTF.Comment: 10 pages, 9 figures, 5 table

Electroweak Precision Constraints on Vector-like Fermions

We calculate the oblique electroweak corrections and confront with the experiments in an extension of the Standard Model. The new fields added are a vector-like weak doublet and a singlet fermion. After electroweak symmetry breaking there is a mixing between the components of the new fields, but no mixing allowed with the standard fermions. Four electroweak parameters, $\hat{S}$, $\hat{T}$, W, Y are presented in the formalism of Barbieri et al., these are the generalization of the Peskin-Takeuchi S, T, U's. The vector-like extension is slightly constrained, $\hat{T}$ requires the new neutral fermion masses not to be very far from each other, allowing higher mass difference for higher masses and smaller mixing. $\hat{S}, W, Y$ gives practically no constraints on the masses. This extension can give a positive contribution to $\hat{T}$, allowing a heavy Higgs boson in electroweak precision tests of the Standard Model.Comment: 11 pages, 3 figures, references added,sign correction, conclusion about heavy Higgs has change

Muon and Cosmogenic Neutron Detection in Borexino

Borexino, a liquid scintillator detector at LNGS, is designed for the detection of neutrinos and antineutrinos from the Sun, supernovae, nuclear reactors, and the Earth. The feeble nature of these signals requires a strong suppression of backgrounds below a few MeV. Very low intrinsic radiogenic contamination of all detector components needs to be accompanied by the efficient identification of muons and of muon-induced backgrounds. Muons produce unstable nuclei by spallation processes along their trajectory through the detector whose decays can mimic the expected signals; for isotopes with half-lives longer than a few seconds, the dead time induced by a muon-related veto becomes unacceptably long, unless its application can be restricted to a sub-volume along the muon track. Consequently, not only the identification of muons with very high efficiency but also a precise reconstruction of their tracks is of primary importance for the physics program of the experiment. The Borexino inner detector is surrounded by an outer water-Cherenkov detector that plays a fundamental role in accomplishing this task. The detector design principles and their implementation are described. The strategies adopted to identify muons are reviewed and their efficiency is evaluated. The overall muon veto efficiency is found to be 99.992% or better. Ad-hoc track reconstruction algorithms developed are presented. Their performance is tested against muon events of known direction such as those from the CNGS neutrino beam, test tracks available from a dedicated External Muon Tracker and cosmic muons whose angular distribution reflects the local overburden profile. The achieved angular resolution is 3-5 deg and the lateral resolution is 35-50 cm, depending on the impact parameter of the crossing muon. The methods implemented to efficiently tag cosmogenic neutrons are also presented.Comment: 42 pages. 32 figures on 37 files. Uses JINST.cls. 1 auxiliary file (defines.tex) with TEX macros. submitted to Journal of Instrumentatio