Spectrally resolved surface plasmon resonance dispersion using half-ball optics

In this work, a variant of a Kretschmann-type surface plasmon resonance (SPR) sensor is introduced. k-space imaging is combined with half-ball glass optics to facilitate the measurement of SPRs across the visible spectral range. In contrast to current state-of-the-art techniques, which are widely utilized in commercially available systems, the presented method allows single-shot-acquisition of the full angular reflection without any moving parts, as well as mapping of the surface plasmon dispersion by scanning across the entire visible wavelength range. Measurements on various thin metallic films demonstrate the sensitivity of the system towards minute changes of the metal surface and its close vicinity. The fast and precise measurement of surface plasmon resonances paves the way for improved detection in applications such as immunoassays or gas-sensors, especially for real-time in situ measurements.</jats:p

Gyroid Optical Metamaterials: Calculating the Effective Permittivity of Multidomain Samples

Gold gyroid optical metamaterials are known to possess a reduced plasma frequency and linear dichroism imparted by their intricate subwavelength single gyroid morphology. The anisotropic optical properties are, however, only evident when a large individual gyroid domain is investigated. Multidomain gyroid metamaterials, fabricated using a polyisoprene-$b$-polystyrene-$b$-poly(ethylene oxide) triblock terpolymer and consisting of multiple small gyroid domains with random orientation and handedness, instead exhibit isotropic optical properties. Comparing three effective medium models, we here show that the specular reflectance spectra of such multidomain gyroid optical metamaterials can be accurately modeled over a broad range of incident angles by a Bruggeman effective medium consisting of a random wire array. This model accurately reproduces previously published results tracking the variation in normal incidence reflectance spectra of gold gyroid optical metamaterials as a function of host refractive index and volume fill fraction of gold. The effective permittivity derived from this theory confirms the change in sign of the real part of the permittivity in the visible spectral region (so, that gold gyroid metamaterials exhibit both dielectric and metallic behavior at optical wavelengths). That a Bruggeman effective medium can accurately model the experimental reflectance spectra implies that small multidomain gold gyroid optical metamaterials behave both qualitatively and quantitatively as an amorphous composite of gold and air (i.e., nanoporous gold) and that coherent electromagnetic contributions arising from the subwavelength gyroid symmetry are not dominant.This research was supported through the Swiss National Science Foundation through the National Center of Competence in Research Bio-Inspired Materials and grant numbers 200021_163220 (to U.S.) and PZ00P2_168223 (to B.D.W.), the Adolphe Merkle Foundation, the Engineering and Physical Sciences Research Council (EPSRC) through the Cambridge NanoDTC EP/G037221/1, EP/L027151/1, and EP/ G060649/1, and ERC LINASS 320503 and from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie grant agreement no. 706329 (to I.G.). Y.G. and U.W. thank the National Science Foundation (DMR-1409105) for financial support

Combined intermittent hypoxia and surface muscle electrostimulation as a method to increase peripheral blood progenitor cell concentration

Background: Our goal was to determine whether short-term intermittent hypoxia exposure, at a level well tolerated by healthy humans and previously shown by our group to increase EPO and erythropoiesis, could mobilizehematopoietic stem cells (HSC) and increase their presence in peripheral circulation. Methods: Four healthy male subjects were subjected to three different protocols: one with only a hypoxic stimulus (OH), another with a hypoxic stimulus plus muscle electrostimulation (HME) and the third with only muscle electrostimulation (OME). Intermittent hypobaric hypoxia exposureconsisted of only three sessions of three hours at barometric pressure 540 hPa (equivalent to an altitude of 5000 m) for three consecutive days, whereas muscular electrostimulation was performed in two separate periods of 25 min in each session. Blood samples were obtained from an antecubital vein on three consecutive days immediately before the experiment and 24 h, 48 h, 4 days and 7 days after the last day of hypoxic exposure. Results: There was a clear increase in the number of circulating CD34+ cells after combined hypobaric hypoxia and muscular electrostimulation. This response was not observed after the isolated application of the same stimuli. Conclusion: Our results open a new application field for hypobaric systems as a way to increase efficiency in peripheral HSC collection

Views on primary prevention of cardiovascular disease - an interview study with Swedish GPs

Background: General practitioners (GPs) have gradually become more involved in the prevention of cardiovascular disease (CVD), both through more frequent prescribing of pharmaceuticals and by giving advice regarding lifestyle factors. Most general practitioners are now faced with decisions about pharmaceutical or non-pharmaceutical treatment for primary prevention every day. The aim of this study was to explore, structure and describe the views on primary prevention of cardiovascular disease in clinical practice among Swedish GPs. Methods: Individual interviews were conducted with 21 GPs in southern Sweden. The interview transcripts were analysed using a qualitative approach, inspired by phenomenography. Results: Two main categories of description emerged during the analysis. One was the degree of reliance on research data regarding the predictability of real risk and the opportunities for primary prevention of CVD. The other was the allocation of responsibility between the patient and the doctor. The GPs showed different views, from being convinced of an actual and predictable risk for the individual to strongly doubting it; from relying firmly on protection from disease by pharmaceutical treatment to strongly questioning its effectiveness in individual cases; and from reliance on prevention of disease by non-pharmaceutical interventions to a total lack of reliance on such measures. Conclusions: The GPs' different views, regarding the rationale for and practical management of primary prevention of CVD, can be interpreted as a reflection of the complexity of patient counselling in primary prevention in clinical practice. The findings have implications for development and implementation of standard treatment guidelines, regarding long-time primary preventive treatment

Topological Strata of Weighted Complex Networks

The statistical mechanical approach to complex networks is the dominant paradigm in describing natural and societal complex systems. The study of network properties, and their implications on dynamical processes, mostly focus on locally defined quantities of nodes and edges, such as node degrees, edge weights and --more recently-- correlations between neighboring nodes. However, statistical methods quickly become cumbersome when dealing with many-body properties and do not capture the precise mesoscopic structure of complex networks. Here we introduce a novel method, based on persistent homology, to detect particular non-local structures, akin to weighted holes within the link-weight network fabric, which are invisible to existing methods. Their properties divide weighted networks in two broad classes: one is characterized by small hierarchically nested holes, while the second displays larger and longer living inhomogeneities. These classes cannot be reduced to known local or quasilocal network properties, because of the intrinsic non-locality of homological properties, and thus yield a new classification built on high order coordination patterns. Our results show that topology can provide novel insights relevant for many-body interactions in social and spatial networks. Moreover, this new method creates the first bridge between network theory and algebraic topology, which will allow to import the toolset of algebraic methods to complex systems.Comment: 26 pages, 19 figures, 1 tabl

Foundations of Black Hole Accretion Disk Theory

This review covers the main aspects of black hole accretion disk theory. We begin with the view that one of the main goals of the theory is to better understand the nature of black holes themselves. In this light we discuss how accretion disks might reveal some of the unique signatures of strong gravity: the event horizon, the innermost stable circular orbit, and the ergosphere. We then review, from a first-principles perspective, the physical processes at play in accretion disks. This leads us to the four primary accretion disk models that we review: Polish doughnuts (thick disks), Shakura-Sunyaev (thin) disks, slim disks, and advection-dominated accretion flows (ADAFs). After presenting the models we discuss issues of stability, oscillations, and jets. Following our review of the analytic work, we take a parallel approach in reviewing numerical studies of black hole accretion disks. We finish with a few select applications that highlight particular astrophysical applications: measurements of black hole mass and spin, black hole vs. neutron star accretion disks, black hole accretion disk spectral states, and quasi-periodic oscillations (QPOs).Comment: 91 pages, 23 figures, final published version available at http://www.livingreviews.org/lrr-2013-

The immunogenicity and safety of a reduced PRP-content DTPw-HBV/Hib vaccine when administered according to the accelerated EPI schedule

<p>Abstract</p> <p>Background</p> <p>Combination vaccines improve coverage, compliance and effectively introduce new antigens to mass vaccination programmes. This was a phase III, observer-blind, randomized study of GSK Biologicals diphtheria-tetanus-whole cell pertussis vaccine combined with hepatitis B and <it>Haemophilus influenzae </it>type b vaccines, containing a reduced amount of polyribosyl-ribitol-phosphate (PRP) and a DTPw component manufactured at a different site (DTPw-HBV/Hib_2.5[Kft]). The primary aim of this study was to demonstrate that DTPw-HBV/Hib_2.5[Kft] was not inferior to the licensed DTPw-HBV/Hib (<it>Tritanrix</it>(tm)-HepB/<it>Hiberix</it>(tm)) vaccine or the DTPw-HBV/Hib_2.5vaccine, also containing a reduced amount of PRP, with respect to the immune response to the PRP antigen, when administered to healthy infants, according to the Expanded Programme for Immunization (EPI) schedule at 6, 10 and 14 weeks of age.</p> <p>Methods</p> <p>299 healthy infants were randomised to receive either DTPw-HBV/Hib_2.5[Kft] DTPw-HBV/Hib_2.5or DTPw-HBV/Hib according to the 6-10-14 week EPI schedule. Blood samples were analysed prior to the first dose of study vaccine and one month after the third vaccine dose for the analysis of immune responses. Solicited local and general symptoms such as pain, redness and swelling at the injection site and drowsiness and fever, unsolicited symptoms (defined as any additional adverse event) and serious adverse events (SAEs) were recorded up to 20 weeks of age.</p> <p>Results</p> <p>One month after the third vaccine dose, 100% of subjects receiving DTPw-HBV/Hib_2.5[Kft] or DTPw-HBV/Hib and 98.8% of subjects receiving DTPw-HBV/Hib_2.5vaccine had seroprotective levels of anti-PRP antibodies (defined as anti-PRP antibody concentration ≥0.15 μg/ml). Seroprotective antibody concentrations were attained in over 98.9% of subjects for diphtheria, tetanus and hepatitis B. The vaccine response rate to pertussis antigen was at least 97.8% in each group. Overall, the DTPw-HBV/Hib_2.5[Kft] vaccine was well tolerated in healthy infants; no SAEs were reported in any group.</p> <p>Conclusions</p> <p>The DTPw-HBV/Hib_2.5[Kft] vaccine was immunogenic and well-tolerated when administered according to the EPI schedule to Indian infants.</p> <p>Trial registration</p> <p><url>http://www.clinicaltrials.gov</url> NCT00473668</p

IFN-γ-inducible protein of 10 kDa upregulates the effector functions of eosinophils through β2 integrin and CXCR3

<p>Abstract</p> <p>Background</p> <p>Eosinophils play an important role in the pathogenesis of bronchial asthma and its exacerbation. Recent reports suggest the involvement of IFN-γ-inducible protein of 10 kDa (IP-10) in virus-induced asthma exacerbation. The objective of this study was to examine whether CXCR3 ligands including IP-10 modify the effector functions of eosinophils.</p> <p>Methods</p> <p>Eosinophils isolated from the blood of healthy donors were stimulated with CXCR3 ligands and their adhesion to rh-ICAM-1 was then measured using eosinophil peroxidase assays. The generation of eosinophil superoxide anion (O₂^-) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) release was evaluated to determine whether CXCR3 ligands induced eosinophil degranulation. Cytokine and chemokine production by eosinophils was examined using a Bio-plex assay.</p> <p>Results</p> <p>Eosinophil adhesion to ICAM-1 was significantly enhanced by IP-10, which also significantly induced eosinophil O₂^-generation in the presence of ICAM-1. Both the enhanced adhesion and O₂^-generation were inhibited by an anti-β₂integrin mAb or an anti-CXCR3 mAb. Other CXCR3 ligands, such as monokine induced by IFN-γ (Mig) and IFN-inducible T cell α chemoattractant (I-TAC), also induced eosinophil adhesion and O₂^-generation in the presence of ICAM-1. IP-10, but not Mig or I-TAC, increased the release of EDN. IP-10 increased the production of a number of cytokines and chemokines by eosinophils.</p> <p>Conclusions</p> <p>These findings suggest that CXCR3 ligands such as IP-10 can directly upregulate the effector functions of eosinophils. These effects might be involved in the activation and infiltration of eosinophils in the airway of asthma, especially in virus-induced asthma exacerbation.</p

Does mentoring matter: results from a survey of faculty mentees at a large health sciences university

Background: To determine the characteristics associated with having a mentor, the association of mentoring with self-efficacy, and the content of mentor&#x2013;mentee interactions at the University of California, San Francisco (UCSF), we conducted a baseline assessment prior to implementing a comprehensive faculty mentoring program. Method: We surveyed all prospective junior faculty mentees at UCSF. Mentees completed a web-based, 38-item survey including an assessment of self-efficacy and a needs assessment. We used descriptive and inferential statistics to determine the association between having a mentor and gender, ethnicity, faculty series, and self-efficacy. Results: Our respondents (n=464, 56%) were 53% female, 62% white, and 7% from underrepresented minority groups. More than half of respondents (n=319) reported having a mentor. There were no differences in having a mentor based on gender or ethnicity (p&#x2265;0.05). Clinician educator faculty with more teaching and patient care responsibilities were statistically significantly less likely to have a mentor compared with faculty in research intensive series (p&#60;0.001). Having a mentor was associated with greater satisfaction with time allocation at work (p&#60;0.05) and with higher academic self-efficacy scores, 6.07 (sd&#x200A;=&#x200A;1.36) compared with those without a mentor, 5.33 (sd&#x200A;=&#x200A;1.35, p&#60;0.001). Mentees reported that they most often discussed funding with the mentors, but rated highest requiring mentoring assistance with issues of promotion and tenure. Conclusion: Findings from the UCSF faculty mentoring program may assist other health science institutions plan similar programs. Mentoring needs for junior faculty with greater teaching and patient care responsibilities must be addressed

Two Pathways Recruit Telomerase to Saccharomyces cerevisiae Telomeres

The catalytic subunit of yeast telomerase, Est2p, is a telomere associated throughout most of the cell cycle, while the Est1p subunit binds only in late S/G2 phase, the time of telomerase action. Est2p binding in G1/early S phase requires a specific interaction between telomerase RNA (TLC1) and Ku80p. Here, we show that in four telomerase-deficient strains (cdc13-2, est1Ä, tlc1-SD, and tlc1-BD), Est2p telomere binding was normal in G1/early S phase but reduced to about 40–50% of wild type levels in late S/G2 phase. Est1p telomere association was low in all four strains. Wild type levels of Est2p telomere binding in late S/G2 phase was Est1p-dependent and required that Est1p be both telomere-bound and associated with a stem-bulge region in TLC1 RNA. In three telomerase-deficient strains in which Est1p is not Est2p-associated (tlc1-SD, tlc1-BD, and est2Ä), Est1p was present at normal levels but its telomere binding was very low. When the G1/early S phase and the late S/G2 phase telomerase recruitment pathways were both disrupted, neither Est2p nor Est1p was telomere-associated. We conclude that reduced levels of Est2p and low Est1p telomere binding in late S/G2 phase correlated with an est phenotype, while a WT level of Est2p binding in G1 was not sufficient to maintain telomeres. In addition, even though Cdc13p and Est1p interact by two hybrid, biochemical and genetic criteria, this interaction did not occur unless Est1p was Est2p-associated, suggesting that Est1p comes to the telomere only as part of the holoenzyme. Finally, the G1 and late S/G2 phase pathways for telomerase recruitment are distinct and are likely the only ones that bring telomerase to telomeres in wild-type cells