Metal Particles Are Inappropriate for Testing a Postulate of Extrapulmonary Transport

Exposure to ambient air pollution particles has been associated with increased human morbidity and mortality, much of which is nonpulmonary. One proposed explanation of this extrapulmonary tissue injury is a transport of the particles outside of the respiratory tract. In the August 2006 issue of EHP, Elder et al. (2006) tested a postulate of extrapulmonary transport of particulate matter (PM). Specifically, the authors focused on the potential translocation of particles by olfactory neuronal pathways to the central nervous system. Comparable to previous studies on systemic transport of PM, they used a metal particle (i.e., a manganese oxide). Elder et al. measured tissue Mn concentrations in an effort to establish transport of the particle

Entanglement sharing among qudits

Consider a system consisting of n d-dimensional quantum particles (qudits), and suppose that we want to optimize the entanglement between each pair. One can ask the following basic question regarding the sharing of entanglement: what is the largest possible value Emax(n,d) of the minimum entanglement between any two particles in the system? (Here we take the entanglement of formation as our measure of entanglement.) For n=3 and d=2, that is, for a system of three qubits, the answer is known: Emax(3,2) = 0.550. In this paper we consider first a system of d qudits and show that Emax(d,d) is greater than or equal to 1. We then consider a system of three particles, with three different values of d. Our results for the three-particle case suggest that as the dimension d increases, the particles can share a greater fraction of their entanglement capacity.Comment: 4 pages; v2 contains a new result for 3 qudits with d=

Structurally Distinct Active Sites in the Copper(II)-Substituted Aminopeptidases from \u3cem\u3eAeromonas proteolytica\u3c/em\u3e and \u3cem\u3eEscherichia coli\u3c/em\u3e

The aminopeptidase from Aeromonas proteolytica (AAP) was titrated with copper, which bound sequentially at two distinct sites. Both the mono- and disubstituted forms of AAP exhibited catalytic hyperactivity relative to the native dizinc enzyme. Monosubstituted AAP exhibited an axial Cu(II) EPR spectrum with slight pH dependence:  at pH 6.0 g|| = 2.249, g⊥ = 2.055, and A||(63/65Cu) = 1.77 × 10-2 cm-1, whereas at pH 9.65 g|| = 2.245, g⊥ = 2.056, and A||(63/65Cu) = 1.77 × 10-2 cm-1. These data indicate oxygen and nitrogen ligation of Cu. AAP further substituted with copper exhibited a complex signal with features around g ∼ 2 and 4. The features at g ∼ 4 were relatively weak in the B0 ⊥ B1 (perpendicular) mode EPR spectrum but were intense in the B0 || B1 (parallel) mode spectrum. The g ∼ 2 region of the perpendicular mode spectrum exhibited two components, one corresponding to mononuclear Cu(II) with g|| = 2.218, g⊥ = 2.023, and A||(63/65Cu) = 1.55 × 10-2 cm-1 and likely due to adventitious binding of Cu(II) to a site distant from the active site. Excellent simulations were obtained for the second component of the spectrum assuming that two Cu(II) ions experience dipolar coupling corresponding to an inter-copper distance of 5 Å with the two Cu(II) gz directions parallel to each other and at an angle of ∼17° to the inter-copper vector (ℋ = βB·gCuA·SCuA + βB·gCuB·SCuB + [S·A·I]CuA + [S·A·I]CuB + [SCuA·J·SCuB]; g||(CuA,CuB) = 2.218, g⊥(CuA,CuB) = 2.060; A||(CuA,CuB)(63/65Cu) = 1.59 × 10-2 cm-1, Jisotropic = 50 cm-1, rCu-Cu = 4.93 Å, and χ = 17°). The exchange coupling between the two copper ions was found to be ferromagnetic as the signals exhibited Curie law temperature dependence. The Cu−Cu distance of ∼5 Å indicated by EPR was significantly higher than the inter-zinc distance of 3.5 Å in the native enzyme, and the dicopper species therefore represents a novel dinuclear site capable of catalysis of hydrolysis. In contrast to AAP, the related methionyl aminopeptidase from Escherichia coli (EcMetAP) was found to bind only one Cu(II) ion despite possessing a dinuclear binding site motif. A further difference was the marked pH dependence of the signal in EcMetAP, suggestive of a change in ligation. The structural motifs of these two Cu(II)-substituted aminopeptidases provide important insight into the observed catalytic activity

EPR of Cu\u3csup\u3e2+\u3c/sup\u3e Prion Protein Constructs at 2 GHz Using the \u3cem\u3eg\u3c/em\u3e\u3csub\u3e⊥\u3c/sub\u3e Region to Characterize Nitrogen Ligation

A double octarepeat prion protein construct, which has two histidines, mixed with copper sulfate in a 3:2 molar ratio provides at most three imidazole ligands to each copper ion to form a square-planar Cu2+ complex. This work is concerned with identification of the fourth ligand. A new (to our knowledge) electron paramagnetic resonance method based on analysis of the intense features of the electron paramagnetic resonance spectrum in the g⊥ region at 2 GHz is introduced to distinguish between three and four nitrogen ligands. The methodology was established by studies of a model system consisting of histidine imidazole ligation to Cu2+. In this spectral region at 2 GHz (S-band), g-strain and broadening from the possible rhombic character of the Zeeman interaction are small. The most intense line is identified with the MI = +1/2 extra absorption peak. Spectral simulation demonstrated that this peak is insensitive to cupric Ax and Ay hyperfine interaction. The spectral region to the high-field side of this peak is uncluttered and suitable for analysis of nitrogen superhyperfine couplings to determine the number of nitrogens. The spectral region to the low-field side of the intense extra absorption peak in the g⊥ part of the spectrum is sensitive to the rhombic distortion parameters Ax and Ay. Application of the method to the prion protein system indicates that two species are present and that the dominant species contains four nitrogen ligands. A new loop-gap microwave resonator is described that contains ∼1 mL of frozen sample

Tissue Inhibitor of Metalloproteinase–3 (TIMP-3) induces FAS dependent apoptosis in human vascular smooth muscle cells

Over expression of Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) in vascular smooth muscle cells (VSMCs) induces apoptosis and reduces neointima formation occurring after saphenous vein interposition grafting or coronary stenting. In studies to address the mechanism of TIMP-3-driven apoptosis in human VSMCs we find that TIMP-3 increased activation of caspase-8 and apoptosis was inhibited by expression of Cytokine response modifier A (CrmA) and dominant negative FAS-Associated protein with Death Domain (FADD). TIMP-3 induced apoptosis did not cause mitochondrial depolarisation, increase activation of caspase-9 and was not inhibited by over-expression of B-cell Lymphoma 2 (Bcl2), indicating a mitochondrial independent/type-I death receptor pathway. TIMP-3 increased levels of the First Apoptosis Signal receptor (FAS) and depletion of FAS with shRNA showed TIMP-3-induced apoptosis was FAS dependent. TIMP-3 induced formation of the Death-Inducing Signalling Complex (DISC), as detected by immunoprecipitation and by immunofluorescence. Cellular-FADD-like IL-1 converting enzyme-Like Inhibitory Protein (c-FLIP) localised with FAS at the cell periphery in the absence of TIMP-3 and this localisation was lost on TIMP-3 expression with c-FLIP adopting a perinuclear localisation. Although TIMP-3 inhibited FAS shedding, this did not increase total surface levels of FAS but instead increased FAS levels within localised regions at the cell surface. A Disintegrin And Metalloproteinase 17 (ADAM17) is inhibited by TIMP-3 and depletion of ADAM17 with shRNA significantly decreased FAS shedding. However ADAM17 depletion did not induce apoptosis or replicate the effects of TIMP-3 by increasing localised clustering of cell surface FAS. ADAM17-depleted cells could activate caspase-3 when expressing levels of TIMP-3 that were otherwise sub-apoptotic, suggesting a partial role for ADAM17 mediated ectodomain shedding in TIMP-3 mediated apoptosis. We conclude that TIMP-3 induced apoptosis in VSMCs is highly dependent on FAS and is associated with changes in FAS and c-FLIP localisation, but is not solely dependent on shedding of the FAS ectodomain

Cross-sectional comparison of critically ill pediatric patients across hospitals with various levels of pediatric care

BACKGROUND: Inpatient administrative data sources describe the care provided to hospitalized children. The Kids' Inpatient Database (KID) provides nationally representative estimates, while the Pediatric Health Information System (PHIS, a consortium of pediatric facilities) derives more detailed information from revenue codes. The objective was to contextualize a diagnosis and procedure-based definition of critical illness to a revenue-based definition; then compare it across hospitals with different levels of pediatric care. METHODS: This retrospective, cross-sectional study utilized the 2009 KID, and 2009 inpatient discharges from the PHIS database. Patients <21 years of age (excluding neonates) were included to focus on pediatric critical illness. Critical illness was defined as: (1) critical care services (CC services) using diagnosis and procedures codes and (2) intensive care unit (ICU) care using revenue codes. Demographics, invasive procedures, and categories of critical illness were compared using Chi square and survey-weighted methods. The definitions of critical illness were compared in PHIS hospitals. CC services populations identified in General Hospitals, Pediatric Facilities, and Freestanding Children's hospitals (from KID) were compared to those in PHIS hospitals. RESULTS: Among PHIS hospitals, critically ill discharges identified by CC services accounted for 37.7% of ICU care. CC services discharges were younger and had greater proportion of respiratory illness and invasive procedure use. Critically ill patients identified by CC services in PHIS hospitals were statistically similar to those in Freestanding Children's hospitals. Pediatric Facilities and General Hospitals had more adolescents with more traumas. CC services patients in general hospitals had lower use of invasive procedures and predominance of trauma, respiratory illness, mental health issues, and general infections. Freestanding children's hospitals discharged 22% of the estimated 96,700 CC services cases. Similar proportions of critically ill patients were seen in Pediatric Facilities (31%) and General Hospitals (33%). CONCLUSION: The CC services definition captured a more severely ill fraction of critically ill children. Critically ill discharges from PHIS hospitals can likely be extrapolated to Freestanding Children's hospitals and Pediatric Facilities. General Hospitals, which provide a significant amount of pediatric critical care, are different. Studies utilizing administrative data can benefit from multiple data sources, which balance the individual strengths and weaknesses

Entanglement of a Pair of Quantum Bits

The ``entanglement of formation'' of a mixed state of a bipartite quantum system can be defined in terms of the number of pure singlets needed to create the state with no further transfer of quantum information. We find an exact formula for the entanglement of formation for all mixed states of two qubits having no more than two non-zero eigenvalues, and we report evidence suggesting that the formula is valid for all states of this system.Comment: 10 page

Hydrator Therapies for Chronic Bronchitis. Lessons from Cystic Fibrosis

Patients with the chronic bronchitis form of chronic obstructive pulmonary disease and cystic fibrosis share similar clinical features, including mucus obstruction of airways and the development of chronic/recurrent airways infections that often manifest as disease exacerbations. There is growing evidence that these diseases may have parallels in disease pathogenesis as well, including cystic fibrosis transmembrane conductance regulator dysfunction, mucus dehydration, and defective mucociliary clearance. As progress is made in the development of therapies that target the basic defects that lead to cystic fibrosis lung disease, it is possible that similar approaches could also benefit patients with chronic bronchitis. A deeper understanding of how tobacco smoke and other triggers of chronic bronchitis actually lead to disease, and exploration of the concept that therapies that restore cystic fibrosis transmembrane conductance regulator function, mucus hydration, and/or mucociliary clearance may benefit patients with chronic bronchitis, hold the prospect of significant progress in treating this prevalent disease