Integrated waveguides and deterministically positioned nitrogen vacancy centers in diamond created by femtosecond laser writing.

Diamond's nitrogen vacancy (NV) center is an optically active defect with long spin coherence times, showing great potential for both efficient nanoscale magnetometry and quantum information processing schemes. Recently, both the formation of buried 3D optical waveguides and high-quality single NVs in diamond were demonstrated using the versatile femtosecond laser-writing technique. However, until now, combining these technologies has been an outstanding challenge. In this Letter, we fabricate laser-written photonic waveguides in quantum grade diamond which are aligned to within micron resolution to single laser-written NVs, enabling an integrated platform providing deterministically positioned waveguide-coupled NVs. This fabrication technology opens the way toward on-chip optical routing of single photons between NVs and optically integrated spin-based sensing.

Femtosecond laser inscription of Bragg grating waveguides in bulk diamond.

Femtosecond laser writing is applied to form Bragg grating waveguides in the diamond bulk. Type II waveguides are integrated with a single pulse point-by-point periodic laser modification positioned toward the edge of the waveguide core. These photonic devices, operating in the telecommunications band, allow for simultaneous optical waveguiding and narrowband reflection from a fourth-order grating. This fabrication technology opens the way toward advanced 3D photonic networks in diamond for a range of applications.

Role of ion migrations in ultrafast laser written tellurite glass waveguides.

We report on a strong cross migration of ions in a Tellurite (Te) based glass to form waveguides using a high repetition rate femtosecond laser. The tellurite glass matrix was modified using oxides of P, Na and Zn elements of which Te and Na ions play an important role to form waveguides upon laser irradiation. Tellurium was observed to migrate causing a positive index change zone whereas sodium cross migrates to the tellurium deficient zone forming a relatively low index change region. We have used micro-Raman analysis to scan across the waveguide cross-section to understand the state of the glass network and the relation between ion migration and glass densification for waveguiding. We have found that there is an increase in TeO3 units and reduction of TeO4 units in the Te rich zones enabling densification. This work will help guide the new commercial glass manufacturing industries that aim at producing mid-infrared transparent glasses like tellurite, tellurides and chalcogenides for the production of waveguide based devices.

Interleukin 2, but not other common gamma chain-binding cytokines, can reverse the defect in generation of CD4 effector T cells from naive T cells of aged mice.

Development of effectors from naive CD4 cells occurs in two stages. The early stage involves activation and limited proliferation in response to T cell receptor (TCR) stimulation by antigen and costimulatory antigen presenting cells, whereas the later stage involves proliferation and differentiation in response to growth factors. Using a TCR-transgenic (Tg(+)) model, we have examined the effect of aging on effector generation and studied the ability of gamma(c) signaling cytokines to reverse this effect. Our results indicate that responding naive CD4 cells from aged mice, compared with cells from young mice, make less interleukin (IL)-2, expand poorly between days 3 to 5, and give rise to fewer effectors with a less activated phenotype and reduced ability to produce cytokines. When exogenous IL-2 or other gamma(c) signaling cytokines are added during effector generation, the Tg(+) cells from both young and aged mice proliferate vigorously. However, IL-4, IL-7, and IL-15 all fail to restore efficient effector production. Only effectors from aged mice generated in the presence of IL-2 are able to produce IL-2 in amounts equivalent to those produced by effectors generated from young mice, suggesting that the effect of aging on IL-2 production is reversible only in the presence of exogenous IL-2.

Femtosecond laser written optical waveguide amplifier in phospho-tellurite glass.

We report on the first demonstration of an optical waveguide amplifier in phospho-tellurite glass providing net gain at 1.5 µm. The device was fabricated using a high repetition rate femtosecond laser and exhibited internal gain across 100-nm bandwidth covering the entire C + L telecom bands.

SPECT imaging of ischemic myocardium using a technetium-99m-nitroimidazole ligand.

UNLABELLED: This investigation evaluates the efficacy of a 99mTc-labeled nitroimidazole (BMS-181321) in identifying oxygen-deprived tissue in two canine models of myocardial ischemia. METHODS: For both models (A and B), epicardial microvascular oxygen pressure (mPO2) was monitored by measuring the oxygen-dependent quenching of phosphorescence lifetime of Palladium mesotetra (4-carboxyphenyl) porphine. In Model A (beagles, n = 5), BMS-181321 was administered intravenously and a distal branch of the left anterior descending coronary artery (LAD) was ligated completely 40 sec later. Ten minutes later, the ligature was released establishing tissue reoxygenation. In Model B, flow through the LAD was reduced until the mPO2 was about 2 Torr. After bolus administration of BMS-181321 (50-60 mCi), coronary ischemia was continued for a residence period of up to 4 hr. RESULTS: With Model A, SPECT reconstructions revealed a small ischemic area in three of five dogs, however, a transmural accumulation of the compound was evident in the autoradiograms from all dogs. In the two animals in which the defect was not observed by SPECT, the ischemic episode had nominal effects on the ratio of +/- dp/dt (< 4% change as compared to baseline values). In Model B, SPECT reconstructions showed positive images of the oxygen-deprived area within the mid- to apical regions of the left ventricle (n = 5). Autoradiographic analysis showed a transmural association with cells resulting in an ischemic-to-nonischemic ratio of 3.5 +/- 0.4 (n = 4) for animals with similar residence times. CONCLUSION: The results from both models suggest that BMS-181321 provides a noninvasive marker of regional ischemia in the heart and that this compound may have clinical utility for detection of coronary artery disease.

A predictive test for adverse reactions to contrast media. Preliminary results.

In a prospective study, whole blood samples drawn from patients prior to their being injected with contrast media were incubated with zymosan to activate the complement cascade. The samples were tested for various analytes, including C3a, thromboxane B2 (TxB2), beta thromboglobulin and platelet factor 4 (PF4). Of 207 patients receiving contrast media, only eight experienced reactions, which were mild. Levels of the platelet constituents were generally elevated in these patients. Specificity and sensitivity were 89% and 83%, respectively, for the combined TxB2 and PF4 radioimmunoassay data. Using the Wilcoxon-Mann-Whitney rank sum test, both PF4 and TxB2 were collected with RCM reactions at the R less than .05 level. Although preliminary, the results suggest that RCM reactions are predictable by the in vitro test procedures described.

Comparative chemical structure and pharmacokinetics of MRI contrast agents.

The blood clearance kinetics of five gadolinium complexes, Gd(L), were determined in rats and the results interpreted in terms of an open two-compartment pharmacokinetic model. The complexes were tested in vitro for stability in serum and in aqueous solutions of ions that they might encounter in vivo and that might be expected to react with the Gd(L) complexes to produce uncomplexed gadolinium. Reaction with serum was observed in two instances. Chemical structural differences among the chelating ligands appear to govern the overall reactivity of their Gd(L) complexes. It may be inferred from the results that a preferred structural feature of the ligand is the presence of a 12-membered 1,4,7,10-tetraaza macrocycle.

A multi-organ, axially distributed model of capillary permeability for a magnetic resonance imaging contrast agent.

Capillary permeability was resolved from uptake data for eight rat organs with gadoteridol, which is a stable, well-tolerated, nonionic, highly water soluble, gadolinium-containing, magnetic resonance imaging contrast agent. The extracellular kinetics were elucidated with an axially distributed, plasma interstitial fluid model and measured plasma flow, organ plasma volume, and interstitial fluid volume. The molecular and biological properties of gadoteridol and this kinetic model provide magnetic resonance imaging with a tool to begin measuring physiologic processes.

Physicochemical properties, pharmacokinetics, and biodistribution of gadoteridol injection in rats and dogs.

RATIONALE AND OBJECTIVES: The physicochemical properties of gadoteridol, a macrocyclic nonionic gadolinium complex, were studied together with its pharmacokinetics and biodistribution in rats and dogs. METHODS: Studies in rats were conducted after single intravenous injections at 0.1 or 0.35 mmol/kg using 153Gd-labeled gadoteridol or with seven daily doses of 0.1 mmol/kg to examine the levels of residual gadolinium in organs. Nonradioactive biodistribution and excretion studies were performed in dogs following injection at 0.1 mmol/kg. RESULTS: After injection, the dose was rapidly cleared from rat blood and excreted such that more than 90% of the dose appeared in the urine within 4 hr of injection. At 7 and 14 days postinjection, only extremely low levels of gadolinium were observed in liver and bone; these levels were two to eight times lower than the levels reported after the injection of gadopentetate dimeglumine. CONCLUSION: The extracellular distribution and rapid urinary excretion of gadoteridol is in agreement with data obtained with other gadolinium-containing chelates used as intravascular magnetic resonance imaging contrast agents. Differences observed in the long-term retention of gadolinium between gadoteridol and gadopentetate dimeglumine were consistent with the reported greater in vivo resistance to transmetallation of gadolinium macrocycles compared with the linear gadolinium chelate molecules.

Essential role of IL-6 in protection against H1N1 influenza virus by promoting neutrophil survival in the lung.

Influenza virus infection is considered a major worldwide public health problem. Seasonal infections with the most common influenza virus strains (e.g., H1N1) can usually be resolved, but they still cause a high rate of mortality. The factors that influence the outcome of the infection remain unclear. Here, we show that deficiency of interleukin (IL)-6 or IL-6 receptor is sufficient for normally sublethal doses of H1N1 influenza A virus to cause death in mice. IL-6 is necessary for resolution of influenza infection by protecting neutrophils from virus-induced death in the lung and by promoting neutrophil-mediated viral clearance. Loss of IL-6 results in persistence of the influenza virus in the lung leading to pronounced lung damage and, ultimately, death. Thus, we demonstrate that IL-6 is a vital innate immune cytokine in providing protection against influenza A infection. Genetic or environmental factors that impair IL-6 production or signaling could increase mortality to influenza virus infection.

Filipino GN to Filipino RN. A well-developed plan leads to success.

This article describes the authors' experience in designing a hospital orientation program for newly recruited Filipino nurses. The nursing department's educational and administrative efforts helped to orient the newly recruited nurses to the hospital and to nursing practice in the United States and prepared them to pass the NCLEX examination. Specific classes included in the orientation are presented. Topic title, time frame, facilitator, components, and rationale for each class are discussed. Suggestions for timing of recruitment and clinical orientation assignments are given. Staff preparation to Philippine culture and nursing practice is also reviewed. The authors believe this information would assist other nursing departments prepare for recruited Filipino nurses on their staff.

The defects in effector generation associated with aging can be reversed by addition of IL-2 but not other related gamma(c)-receptor binding cytokines.

Aged naive CD4 T cells produce low levels of IL-2, leading to inefficient generation of effectors. The cells expand poorly, giving rise to few effectors with less activated phenotypes and reduced ability to produce cytokines. The aged cells also respond less vigorously in vivo. Addition of exogenous IL-2 or other gamma(c) receptor-signaling cytokines, restores expansion. However, only effectors generated in the presence of IL-2, are able to produce IL-2 in normal amounts and to become polarized to secrete Th2 cytokines. The defect in IL-2 production may be the only critical deficiency of aged naive CD4 T cells. Importantly, memory CD4 T cells generated from the IL-2 "restored" effectors are also deficient in IL-2 production, suggesting that a heritable change occurs during aging which effects production of IL-2 by resting naive and memory CD4 T cells, but not by optimally generated effectors.

The isolation of an antigen binding factor from cultured murine T-lymphocytes.

BALB/c mice were immunized with the random sequence polypeptide [Glu60 Ala40] (GA). 125I-lymphocyte suspensions were prepared from lymph nodes, radiolabelled with 125I and cultured for 18 hours. Supernatant fluids were collected and passed over an immunoabsorbant composed of [D-Glu60 D-Ala40] (D-GA) bound to Sepharose. The non-adherent fraction was then applied to GA Sepharose and the adherent material eluted with 2 M NaSCN. The eluate was relabelled with 125I, reabsorbed to GA Sepharose and eluted. This fraction bound well to GA-Sepharose (50-80%) but not to the enantiomorphic D-GA Sepharose (5-10%). This material did not react with goat antisera directed against murine IgG, IgM or IgA. It was capable of binding to rabbit antiidiotypic sera raised against BALB/c anti-GA, but not to those antibodies raised against BALB/c anti-GAT. It also showed some reaction with rabbit antiserum to a rat T cell factor (TCF). Polyacrylamide gel electrophoresis revealed a major component with an approximate molecular weight of 63,000 which was not affected by reduction and alkylation.

Reciprocal regulation of polarized cytokine production by effector B and T cells.

Although B cells produce cytokines it is not known whether B cells can differentiate into effector subsets that secrete polarized arrays of cytokines. We have identified two populations of "effector" B cells (Be1 and Be2) that produce distinct patterns of cytokines depending on the cytokine environment in which the cells were stimulated during their primary encounter with antigen and T cells. These effector B cell subsets subsequently regulate the differentiation of naïve CD4+ T cells to TH1 and TH2 cells through production of polarizing cytokines such as interleukin 4 and interferon gamma. In addition, Be1 and Be2 cells could be identified in animals that were infected with pathogens that preferentially induce a Type 1 and Type 2 immune response. Together these results suggest that, in addition to their well defined role in antibody production, B cells may regulate immune responses to infectious pathogens through their production of cytokines.