A molecular theory for two-photon and three-photon fluorescence polarization

In the analysis of molecular structure and local order in heterogeneous samples, multiphoton excitation of fluorescence affords chemically specific information and high-resolution imaging. This report presents the results of an investigation that secures a detailed theoretical representation of the fluorescence polarization produced by one-, two-, and three-photon excitations, with orientational averaging procedures being deployed to deliver the fully disordered limits. The equations determining multiphoton fluorescence response prove to be expressible in a relatively simple, generic form, and graphs exhibit the functional form of the multiphoton fluorescence polarization. Amongst other features, the results lead to the identification of a condition under which the fluorescence produced through the concerted absorption of any number of photons becomes completely unpolarized. It is also shown that the angular variation of fluorescence intensities is reliable indicator of orientational disorder

The role of vestibular cues in postural sway

Controlling posture requires continuous sensory feedback about body motion and orientation, including from the vestibular organs. Little is known about the role of tilt vs. translation vs. rotation vestibular cues. We examined whether intersubject differences in vestibular function were correlated with intersubject differences in postural control. Vestibular function was assayed using vestibular direction-recognition perceptual thresholds, which determine the smallest motion that can be reliably perceived by a subject seated on a motorized platform in the dark. In study A, we measured thresholds for lateral translation, vertical translation, yaw rotation, and head-centered roll tilts. In study B, we measured thresholds for roll, pitch, and left anterior-right posterior and right anterior-left posterior tilts. Center-of-pressure (CoP) sway was measured in sensory organization tests (study A) and Romberg tests (study B). We found a strong positive relationship between CoP sway and lateral translation thresholds but not CoP sway and other thresholds. This finding suggests that the vestibular encoding of lateral translation may contribute substantially to balance control. Since thresholds assay sensory noise, our results support the hypothesis that vestibular noise contributes to spontaneous postural sway. Specifically, we found that lateral translation thresholds explained more of the variation in postural sway in postural test conditions with altered proprioceptive cues (vs. a solid surface), consistent with postural sway being more dependent on vestibular noise when the vestibular contribution to balance is higher. These results have potential implications for vestibular implants, balance prostheses, and physical therapy exercises.NEW & NOTEWORTHY Vestibular feedback is important for postural control, but little is known about the role of tilt cues vs. translation cues vs. rotation cues. We studied healthy human subjects with no known vestibular pathology or symptoms. Our findings showed that vestibular encoding of lateral translation correlated with medial-lateral postural sway, consistent with lateral translation cues contributing to balance control. This adds support to the hypothesis that vestibular noise contributes to spontaneous postural sway

Identification of Novel CYP2D7-2D6 Hybrids: Non-Functional and Functional Variants

Polymorphic expression of CYP2D6 contributes to the wide range of activity observed for this clinically important drug metabolizing enzyme. In this report we describe novel CYP2D7/2D6 hybrid genes encoding non-functional and functional CYP2D6 protein and a CYP2D7 variant that mimics a CYP2D7/2D6 hybrid gene. Five-kilobyte-long PCR products encompassing the novel genes were entirely sequenced. A quantitative assay probing in different gene regions was employed to determine CYP2D6 and 2D7 copy number variations and the relative position of the hybrid genes within the locus was assessed by long-range PCR. In addition to the previously known CYP2D6*13 and *66 hybrids, we describe three novel non-functional CYP2D7-2D6 hybrids with gene switching in exon 2 (CYP2D6*79), intron 2 (CYP2D6*80), and intron 5 (CYP2D6*67). A CYP2D7-specific T-ins in exon 1 causes a detrimental frame shift. One subject revealed a CYP2D7 conversion in the 5′-flanking region of a CYP2D6*35 allele, was otherwise unaffected (designated CYP2D6*35B). Finally, three DNAs revealed a CYP2D7 gene with a CYP2D6-like region downstream of exon 9 (designated CYP2D7[REP6]). Quantitative copy number determination, sequence analyses, and long-range PCR mapping were in agreement and excluded the presence of additional gene units. Undetected hybrid genes may cause over-estimation of CYP2D6 activity (CYP2D6*1/*1 vs *1/hybrid, etc), but may also cause results that may interfere with the genotype determination. Detection of hybrid events, “single” and tandem, will contribute to more accurate phenotype prediction from genotype data

Rapid spatiotemporal variations in rift structure during development of the Corinth Rift, central Greece

The Corinth Rift, central Greece, enables analysis of early rift development as it is young (<5Ma) and highly active and its full history is recorded at high resolution by sedimentary systems. A complete compilation of marine geophysical data, complemented by onshore data, is used to develop a high-resolution chronostratigraphy and detailed fault history for the offshore Corinth Rift, integrating interpretations and reconciling previous discrepancies. Rift migration and localization of deformation have been significant within the rift since inception. Over the last circa 2Myr the rift transitioned from a spatially complex rift to a uniform asymmetric rift, but this transition did not occur synchronously along strike. Isochore maps at circa 100kyr intervals illustrate a change in fault polarity within the short interval circa 620-340ka, characterized by progressive transfer of activity from major south dipping faults to north dipping faults and southward migration of discrete depocenters at ~30m/kyr. Since circa 340ka there has been localization and linkage of the dominant north dipping border fault system along the southern rift margin, demonstrated by lateral growth of discrete depocenters at ~40m/kyr. A single central depocenter formed by circa 130ka, indicating full fault linkage. These results indicate that rift localization is progressive (not instantaneous) and can be synchronous once a rift border fault system is established. This study illustrates that development processes within young rifts occur at 100kyr timescales, including rapid changes in rift symmetry and growth and linkage of major rift faults

Nicotinamide Phosphoribosyltransferase Attenuates Methotrexate Response in Juvenile Idiopathic Arthritis and In Vitro

Variability in response to methotrexate (MTX) in the treatment of juvenile idiopathic arthritis (JIA) remains unpredictable and poorly understood. Based on previous studies implicating an interaction between nicotinamide phosphoribosyltransferase (NAMPT) expression and MTX therapy in inflammatory arthritis, we hypothesized that increased NAMPT expression would be associated with reduced therapeutic response to MTX in patients with JIA. A significant association was found between increased plasma concentrations of NAMPT and reduced therapeutic response in patients with JIA treated with MTX. Inhibition of NAMPT in cell culture by either siRNA-based gene silencing or pharmacological inhibition with FK-866 was found to result in a fourfold increase in the pharmacological activity of MTX. Collectively, these findings provide evidence that NAMPT inhibits the pharmacological activity of MTX and may represent a predictive biomarker of response, as well as a therapeutic target, in the treatment of JIA with MTX

‘I’m not the police’: Practical strategies for sport coach mentors to develop trust and trustworthiness

This paper examines trust and trustworthiness in sport coach mentor-mentee relationships. Specifically, we investigate the place and importance of trust from the mentor’s perspective and establish how trustworthy impressions are actively developed. Guided by the theoretical ideas of Hardin (2002) and Hoy and Tschannen-Moran (1999), we conducted 18 online, two-to-one semi-structured interviews with nine mentors affiliated with two National Governing Bodies (NGBs) of sport. Data were subjected to a phronetic, iterative analysis, which involved inductive and deductive sensemaking and an interactive writing process. Key findings suggested a) that the mentors defined trust as a crucial construct in the development of mentee motivation, learning, and engagement, b) establishing trustworthy impressions was important for the mentors’ material and non-material interests, c) mentors reported how mentees were initially aloof due to an apparent distrust of NGBs, and d) mentors used numerous interactional strategies to create trustworthy impressions. These included i) deformalising mentor-mentee relationships, ii) actively demonstrating reliability as mentors, iii) using mutually beneficial lies to simultaneously secure buy-in and build mentee confidence and self-esteem, iv) illustrating their own fallibility as sport coaches, v) considering the value of displaying their own coaching competency, and vi) developing mentees’ competencies through empowerment. The findings offer practical strategies for NGBs and other [non]sporting bodies to support mentors in creating trustworthy impressions and build successful mentoring relationships

Enhancing Optical Up-Conversion Through Electrodynamic Coupling with Ancillary Chromophores

In lanthanide-based optical materials, control over the relevant operating characteristics–for example transmission wavelength, phase and quantum efficiency–is generally achieved through the modification of parameters such as dopant/host combination, chromophore concentration and lattice structure. An alternative avenue for the control of optical response is through the introduction of secondary, codoped chromophores. Here, such secondary centers act as mediators, commonly bridging the transfer of energy between primary absorbers of externally sourced optical input and other sites of frequency-converted emission. Utilizing theoretical models based on experimentally feasible, three-dimensional crystal lattice structures; a fully quantized theoretical framework provides insights into the locally modified mechanisms that can be implemented within such systems. This leads to a discussion of how such effects might be deployed to either enhance, or potentially diminish, the efficiency of frequency up-conversion

Laser-controlled fluorescence in two-level systems

The ability to modify the character of fluorescent emission by a laser-controlled, optically nonlinear process has recently been shown theoretically feasible, and several possible applications have already been identified. In operation, a pulse of off-resonant probe laser beam, of sufficient intensity, is applied to a system exhibiting fluorescence, during the interval of excited- state decay following the initial excitation. The result is a rate of decay that can be controllably modified, the associated changes in fluorescence behavior affording new, chemically specific information. In this paper, a two-level emission model is employed in the further analysis of this all-optical process; the results should prove especially relevant to the analysis and imaging of physical systems employing fluorescent markers, these ranging from quantum dots to green fluorescence protein. Expressions are presented for the laser-controlled fluorescence anisotropy exhibited by samples in which the fluorophores are randomly oriented. It is also shown that, in systems with suitably configured electronic levels and symmetry properties, fluorescence emission can be produced from energy levels that would normally decay nonradiatively. © 2010 American Chemical Society

Identifying the science and technology dimensions of emerging public policy issues through horizon scanning

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security

Sources of evidence in HIV/AIDS care: pilot study comparing family physicians and AIDS service organization staff

BACKGROUND: The improvement of the quality of the evidence used in treatment decision-making is especially important in the case of patients with complicated disease processes such as HIV/AIDS for which multiple treatment strategies exist with conflicting reports of efficacy. Little is known about the perceptions of distinct groups of health care workers regarding various sources of evidence and how these influence the clinical decision-making process. Our objective was to investigate how two groups of treatment information providers for people living with HIV/AIDS perceive the importance of various sources of treatment information. METHODS: Surveys were distributed to staff at two local AIDS service organizations and to family physicians at three community health centres treating people living with HIV/AIDS. Participants were asked to rate the importance of 10 different sources of evidence for HIV/AIDS treatment information on a 5-point Likert-type scale. Mean rating scores and relative rankings were compared. RESULTS: Findings suggest that a discordance exists between the two health information provider groups in terms of their perceptions of the various sources of evidence. Furthermore, AIDS service organization staff ranked health care professionals as the most important source of information whereas physicians deemed AIDS service organizations to be relatively unimportant. The two groups appear to share a common mistrust for information from pharmaceutical industries. CONCLUSIONS: Discordance exists between medical "experts" from different backgrounds relating to their perceptions of evidence. Further investigation is warranted in order to reveal any effects on the quality of treatment information and implications in the decision-making process. Possible effects on collaboration and working relationships also warrant further exploration