An activity-based near-infrared glucuronide trapping probe for imaging β-glucuronidase expression in deep tissues

β-glucuronidase is an attractive reporter and prodrug-converting enzyme. The development of near-IR (NIR) probes for imaging of β-glucuronidase activity would be ideal to allow estimation of reporter expression and for personalized glucuronide prodrug cancer therapy in preclinical studies. However, NIR glucuronide probes are not yet available. In this work, we developed two fluorescent probes for detection of β-glucuronidase activity, one for the NIR range (containing IR-820 dye) and the other for the visible range [containing fluorescein isothiocyanate (FITC)], by utilizing a difluoromethylphenol-glucuronide moiety (TrapG) to trap the fluorochromes in the vicinity of the active enzyme. β-glucuronidase-mediated hydrolysis of the glucuronyl bond of TrapG generates a highly reactive alkylating group that facilitates the attachment of the fluorochrome to nucleophilic moieties located near β-glucuronidase-expressing sites. FITC-TrapG was selectively trapped on purified β-glucuronidase or β-glucuronidase-expressing CT26 cells (CT26/mβG) but not on bovine serum albumin or non-β-glucuronidase-expressing CT26 cells used as controls. β-glucuronidase-activated FITC-TrapG did not interfere with β-glucuronidase activity and could label bystander proteins near β-glucuronidase. Both FITC-TrapG and NIR-TrapG specifically imaged subcutaneous CT26/mβG tumors, but only NIR-TrapG could image CT26/mβG tumors transplanted deep in the liver. Thus NIR-TrapG may provide a valuable tool for visualizing β-glucuronidase activity in vivo.     

Detecting Higgs bosons with muons at hadron colliders

We investigate the prospects for the discovery of neutral Higgs bosons with a pair of muons by direct searches at the CERN large hadron collider (LHC) as well as by indirect searches in the rare decay Bs→μ⁺μ⁻$B_s\to {\mu }^{+}{\mu }^{-}$ at the Fermilab Tevatron and the LHC. Promising results are found for the minimal supersymmetric standard model, the minimal supergravity (mSUGRA) model, and supergravity models with non-universal Higgs masses (NUHM SUGRA). For tanβ?50$\tan \beta ?50$, we find that (i) the contours for a branching fraction of B(Bs→μ⁺μ⁻)=1×¹⁰⁻⁸$B(B_s\to {\mu }^{+}{\mu }^{-})=1\times {10}^{\mathrm{-8}}$ in the parameter space are very close to the 5σ   contours for pp→b?⁰→bμ⁺μ⁻+X$pp\to b{?}^0\to b{\mu }^{+}{\mu }^{-}+X$, ?⁰=h⁰${?}^0=h^0$, H⁰$H^0$, A⁰$A^0$ at the LHC with an integrated luminosity (L) of 30 fb⁻¹, (ii) the regions covered by B(Bs→μ⁺μ⁻)?5×¹⁰⁻⁹$B(B_s\to {\mu }^{+}{\mu }^{-})?5\times {10}^{\mathrm{-9}}$ and the discovery region for b?⁰→bμ⁺μ⁻$b{?}^0\to b{\mu }^{+}{\mu }^{-}$ with 300 fb⁻¹ are complementary in the mSUGRA parameter space, (iii) in NUHM SUGRA models, a discovery of B(Bs→μ⁺μ⁻)?5×¹⁰⁻⁹$B(B_s\to {\mu }^{+}{\mu }^{-})?5\times {10}^{\mathrm{-9}}$ at the LHC will cover regions of the parameter space beyond the direct search for b?⁰→bμ⁺μ⁻$b{?}^0\to b{\mu }^{+}{\mu }^{-}$ with L=300 fb⁻¹$L=300{\text{fb}}^{\mathrm{-1}}$.     

Induced random fields in the LiHoxY1-xF4 quantum Ising magnet in a transverse magnetic field

The LiHoxY1-xF4 magnetic material in a transverse magnetic field Bx x perpendicular to the Ising spin direction has long been used to study tunable quantum phase transitions in a random disordered system. We show that the Bx-induced magnetization along the x direction, combined with the local random dilution-induced destruction of crystalline symmetries, generates, via the predominant dipolar interactions between Ho3+ ions, random fields along the Ising z direction. This identifies LiHoxY1-xF4 in Bx as a new random field Ising system. The random fields explain the rapid decrease of the critical temperature in the diluted ferromagnetic regime and the smearing of the nonlinear susceptibility at the spin-glass transition with increasing Bx and render the Bx-induced quantum criticality in LiHoxY1-xF4 likely inaccessible.     

Dissociation of heme from gaseous myoglobin ions studied by infrared multiphoton dissociation spectroscopy and Fourier-transform ion cyclotron resonance mass spectrometry

Detachment of heme prosthetic groups from gaseous myoglobin ions has been studied by collision-induced dissociation and infrared multiphoton dissociation in combination with Fourier-transform ion cyclotron resonance mass spectrometry. Multiply charged holomyoglobin ions (hMbn+) were generated by electrospray ionization and transferred to an ion cyclotron resonance cell, where the ions of interest were isolated and fragmented by either collision with Ar atoms or irradiation with 3 mum photons, producing apomyoglobin ions (aMbn+). Both charged heme loss (with [Fe(III)-heme]+ and aMb(n-1)+ as the products) and neutral heme loss (with [Fe(II)-heme] and aMbn+ as the products) were detected concurrently for hMbn+ produced from a myoglobin solution pretreated with reducing reagents. By reference to Ea = 0.9 eV determined by blackbody infrared radiative dissociation for charged heme loss of ferric hMbn+, an activation energy of 1.1 eV was deduced for neutral heme loss of ferrous hMbn+ with n = 9 and 10.