Development of a backward-mode photoacoustic microscope using a Fabry-Perot sensor

Optical-resolution photoacoustic microscopy (PAM) has been shown to enable the acquisition of high resolution (μm) functional and anatomical images. For backward-mode operation, conventional piezoelectric ultrasound transducers need to be placed far away from the signal source due to their opacity and size. This can result in reduced acoustic sensitivity. Planar Fabry-Perot polymer film interferometer (FPI) sensors have the potential to overcome this limitation since they are transparent to the excitation wavelength, can be placed immediately adjacent to the signal source for high acoustic sensitivity, and offer a broadband frequency response (0 –50 MHz). In this study, we present a high frame rate, backward-mode OR-PAM system based on a planar FPI ultrasound sensor. A ns-pulsed laser provides excitation pulses (<200 nJ, maximum pulse repetition frequency = 200 kHz, 532 nm) to generate photoacoustic waves that are detected using a planar FPI sensor interrogated at 765-781 nm. For backwardmode operation and highest acoustic sensitivity, the excitation and interrogation beams are coaxially aligned and rasterscanned. The optical transfer function of the sensor, the spatial resolution and the detection sensitivity were determined to characterise the set-up. Images of a leaf phantom and first in vivo images of zebrafish larvae were acquired. This approach will enable fast 3D OR-PAM with high resolution and high sensitivity for functional and molecular imaging applications. FPI-based ultrasound detection also has the potential to enable dual-mode optical- and acousticresolution PAM and the integration of photoacoustic imaging with purely optical modalities such as multi-photon microscopy

Importance of exposure route for behavioural responses in Lumbriculus variegatus Müller (Oligochaeta: Lumbriculida) in short-term exposures to Pb

Abstract Goal, Scope and Background Lumbriculus variegatus Müller (Oligochaeta), a common freshwater sediment-dweller, has frequently been used in toxicokinetic studies, although has been less used in ecotoxicity tests. Methods For the first time the Multispecies Freshwater Biomonitor® (MFB) was applied in a short-term whole-sediment toxicity test. The MFB automatically and quantitatively recorded the spontaneous locomotory behaviour of Lumbriculus variegatus in exposures with two compartments, water and sediment. The study questioned, whether the animals altered their locomotion depending on the compartment which was spiked with lead (Pb). Results and Discussion As in the exposures to Pb-contaminated water/clean sediment, the animals exposed to Pb-contaminated sediment/clean water showed higher activities in intermediate Pb-concentrations. This indicates, that spontaneous locomotory activity is affected by Pb-concentrations at sublethal levels regardless of whether the Pb-concentration is found in the water or in the sediment, because these animals use both environmental compartments simultaneously. However, within the same Pb-levels, the animals showed higher locomotory activity in contaminated water compared with contaminated sediment. This indicates a possible tendency to withdraw from (‘avoidance’) contaminated water into the clean sediment compartment, whereas there was no withdrawal from contaminated sediment into clean water. The latter might be explained by the fact that withdrawal from sediment to water might increase the risk of predation and drift in nature, whereas retracting to sediment might provide shelter. Conclusions The study showed that spontaneous locomotory responses of L. variegatus to Pb depend on whether the water or sediment is contaminated. The study also concluded that the Multispecies Freshwater Biomonitor® can be applied effectively in sediment toxicity testing. Recommendations and Perspectives More emphasis should be given to the interactions of water/sediment in sediment ecotoxicity tests to better simulate field conditions and increase ecological realism in risk assessment, especially as quantitative recording methods exisit

Renal impairment after liver transplantation - a pilot trial of calcineurin inhibitor-free vs. calcineurin inhibitor sparing immunosuppression in patients with mildly impaired renal function after liver transplantation

<p>Abstract</p> <p>Objectives</p> <p>Chronic kidney disease is frequent in patients after orthotopic liver transplantation (OLT) and has impact on survival. Patients receiving calcineurin inhibitors (CNI) are at increased risk to develop impaired renal function. Early CNI reduction and concomitant use of mycophenolat mofetil (MMF) has been shown to improve renal function.</p> <p>Methods</p> <p>The aim of this trial was to compare dose-reduced CNI/MMF versus CNI-free MMF/prednisone-based treatment in stable patients after OLT with respect to glomerular filtration rate (GFR). 21 patients [GFR 44.9 ± 9.9 mL/min/1.73 m²measured by 99m-Tc-DTPA-clearance, serum creatinine (SCr) 1.5 ± 0.42 mg/dL] were randomized either to exchange CNI for 10 mg prednisone (group 1; n = 8) or to receive CNI at 25% of the initial dose (group 2; n = 13) each in combination with 1000 mg MMF b.i.d.</p> <p>Results</p> <p>At month 12 mean SCr (-0.3 ± 0.4 mg/dL, p = 0.031) and GFR improved (8.6 ± 13.1 mL/min/1.73 m², p = 0.015) in group 2 but remained unchanged in group 1. Main side effects were gastroinstestinal symptoms (14.3%) and infections (4.8%). Two biopsy proven, steroid-responsive rejections occurred. In group 1 mean diastolic blood pressure (BP) increased by 11 ± 22 mmHg (p = 0.03).</p> <p>Conclusions</p> <p>Reduced dose CNI in combination with MMF but not CNI-free-immunosuppression leads to improvement of GFR in patients with moderately elevated SCr levels after OLT. Addition of steroids resulted in increased diastolic blood pressure presumably counterbalancing the benefits of CNI withdrawal on renal function.</p

`In pursuit of the Nazi mind?' the deployment of psychoanalysis in the allied struggle against Germany

This paper discusses how psychoanalytic ideas were brought to bear in the Allied struggle against the Third Reich and explores some of the claims that were made about this endeavour. It shows how a variety of studies of Fascist psychopathology, centred on the concept of superego, were mobilized in military intelligence, post-war planning and policy recommendations for ‘denazification’. Freud's ideas were sometimes championed by particular army doctors and government planners; at other times they were combined with, or displaced by, competing, psychiatric and psychological forms of treatment and diverse studies of the Fascist ‘personality’. This is illustrated through a discussion of the treatment and interpretation of the deputy leader of the Nazi Party, Rudolf Hess, after his arrival in Britain in 1941

Dynamical Structure Factors of the S=1/2 Bond-Alternating Spin Chain with a Next-Nearest-Neighbor Interaction in Magnetic Fields

The dynamical structure factor of the S=1/2 bond-alternating spin chain with a next-nearest-neighbor interaction in magnetic field is investigated using the continued fraction method based on the Lanczos algorithm. When the plateau exists on the magnetization curve, the longitudinal dynamical structure factor shows a large intensity with a periodic dispersion relation, while the transverse one shows a large intensity with an almost dispersionless mode. The periodicity and the amplitude of the dispersion relation in the longitudinal dynamical structure factor are sensitive to the coupling constants. The dynamical structure factor of the S=1/2 two-leg ladder in magnetic field is also calculated in the strong interchain-coupling regime. The dynamical structure factor shows gapless or gapful behavior depending on the wave vector along the rung.Comment: 8 pages, 4 figures, to appear in Journal of the Physical Society of Japan, vol. 69, no. 10, (2000

Systems analysis of cancer cell heterogeneity in caspase-dependent apoptosis subsequent to mitochondrial outer membrane permeabilization.

Deregulation of apoptosis is a hallmark of carcinogenesis. We here combine live cell imaging and systems modeling to investigate caspase-dependent apoptosis execution subsequent to mitochondrial outer membrane permeabilization (MOMP) in several cancer cell lines. We demonstrate that, although most cell lines that underwent MOMP also showed robust and fast activation of executioner caspases and apoptosis, the colorectal cancer cell lines LoVo and HCT-116 Smac(-/-), similar to X-linked inhibitor of apoptosis protein (XIAP)-overexpressing HeLa (HeLa XIAP(Adv)) cells, only showed delayed and often no caspase activation, suggesting apoptosis impairment subsequent to MOMP. Employing APOPTO-CELL, a recently established model of apoptosis subsequent to MOMP, this impairment could be understood by studying the systemic interaction of five proteins that are present in the apoptosis pathway subsequent to MOMP. Using APOPTO-CELL as a tool to study detailed molecular mechanisms during apoptosis execution in individual cell lines, we demonstrate that caspase-9 was the most important regulator in DLD-1, HCT-116, and HeLa cells and identified additional cell line-specific co-regulators. Developing and applying a computational workflow for parameter screening, systems modeling identified that apoptosis execution kinetics are more robust against changes in reaction kinetics in HCT-116 and HeLa than in DLD-1 cells. Our systems modeling study is the first to draw attention to the variability in cell specific protein levels and reaction rates and to the emergent effects of such variability on the efficiency of apoptosis execution and on apoptosis impairment subsequent to MOMP

How are social stressors at work related to well-being and health? A systematic review and meta-analysis

Background: Social relationships are crucial for well-being and health, and considerable research has established social stressors as a risk for well-being and health. However, researchers have used many different constructs, and it is unclear if these are actually different or reflect a single overarching construct. Distinct patterns of associations with health/well-being would indicate separate constructs, similar patterns would indicate a common core construct, and remaining differences could be attributed to situational characteristics such as frequency or intensity. The current meta-analysis therefore investigated to what extent different social stressors show distinct (versus similar) patterns of associations with well-being and health. Methods: We meta-analysed 557 studies and investigated correlations between social stressors and outcomes in terms of health and well-being (e.g. burnout), attitudes (e.g. job satisfaction), and behaviour (e.g. counterproductive work behaviour). Moderator analyses were performed to determine if there were differences in associations depending on the nature of the stressor, the outcome, or both. To be included, studies had to be published in peer-reviewed journals in English or German; participants had to be employed at least 50% of a full-time equivalent (FTE). Results: The overall relation between social stressors and health/well-being was of medium size (r = -.30, p < .001). Type of social stressor and outcome category acted as moderators, with moderating effects being larger for outcomes than for stressors. The strongest effects emerged for job satisfaction, burnout, commitment, and counterproductive work behaviour. Type of stressor yielded a significant moderation, but differences in effect sizes for different stressors were rather small overall. Rather small effects were obtained for physical violence and sexual mistreatment, which is likely due to a restricted range because of rare occurrence and/or underreporting of such intense stressors. Conclusions: We propose integrating diverse social stressor constructs under the term "relational devaluation" and considering situational factors such as intensity or frequency to account for the remaining variance. Practical implications underscore the importance for supervisors to recognize relational devaluation in its many different forms and to avoid or minimize it as far as possible in order to prevent negative health-related outcomes for employees

Childcare, choice and social class: Caring for young children in the UK

This paper draws on the results of two qualitative research projects examining parental engagements with the childcare market in the UK. Both projects are located in the same two London localities. One project focuses on professional middle class parents, and the other on working class families, and we discuss the key importance of social class in shaping parents' differential engagement with the childcare market, and their understandings of the role childcare plays in their children's lives. We identify and discuss the different "circuits" of care (Ball et al 1995) available to and used by families living physically close to each other, but in social class terms living in different worlds. We also consider parents' relationships with carers, and their social networks. We conclude that in order to fully understand childcare policies and practices and families' experiences of care, an analysis which encompasses social class and the workings of the childcare market is needed

Correlation functions for 1d interacting fermions with spin-orbit coupling

We compute correlation functions for one-dimensional electron systems which spin and charge degrees of freedom are coupled through spin-orbit coupling. Charge density waves, spin density waves, singlet- triplet- superconducting fluctuations are studied. We show that the spin-orbit interaction modify the exponents and the phase diagram of the system, changing the dominant fluctuations and making new susceptibilities diverge for low temperature.Comment: 5 pages, 3 figures. Accepted for publication in Phys. Rev.

Zika virus impairs the development of blood vessels in a mouse model of congenital infection

Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly