Image formation and tomogram reconstruction in optical coherence microscopy

In this work we present a model for image formation in optical coherence microscopy. In the spectral domain detection, each wavenumber has a specific coherent transfer function that samples a different part of the object's spatial frequency spectrum. The reconstruction of the tomogram is usually accurate only in a short depth of field. Using numerical simulations based on the developed model, we identified two distinct mechanisms that influence the signal of out-of-focus sample information. Besides the lateral blurring induced through defocusing, an additional axial envelope contributing equally to the signal degradation was found. (C) 2010 Optical Society of Americ

Coherent transfer functions and extended depth of field

To preserve the speed advantage of Fourier Domain detection in Optical Coherence Microscopy (OCM), extended depth of field is needed. With a narrow probing volume that extends over a long axial range, tissue could be measured in vivo and at cellular resolution. To assess and improve the DOF and the lateral resolution, we analyzed the coherent transfer function (CTF) of OCM. Both the illumination and detection optics contribute equally to the overall imaging performance. In the Fourier domain detection, each pixel of the spectrometer has its specific CTF, sampling a different region of the object’s spatial frequency spectrum. For classical optics and increasing numerical apertures these regions start to overlap and bend, which limits the depth of field. Annular apertures, created with Bessel-like beams produced by axicon lenses or phase filters, circumvent these detrimental effects, but introduce strong side lobes. Decoupling the detection and the illumination apertures is needed to provide the flexibility in engineering a CTF that optimizes the lateral resolution and the DOF at the same time all while reducing these side lobes. We evaluated different combinations of Gaussian and Bessel-like illumination and detection optics, both theoretically and experimentally. Using Bessel-like beams as well in the illumination as in the detection paths, but with annular apertures of different lobe radii, we obtained a lateral resolution of 1.3 μm and an extended depth of field of more than 300 μm, which was completely decoupled from the numerical aperture and scalable to high lateral resolution

Lagrangian formation pathways of moist anomalies in the trade-wind region during the dry season: two case studies from EUREC4A

Shallow clouds in the trade-wind region over the North Atlantic contribute substantially to the global radiative budget. In the vicinity of the Caribbean island of Barbados, they appear in different mesoscale organization patterns with distinct net cloud radiative effects (CREs). Cloud formation processes in this region are typically controlled by the prevailing large-scale subsidence. However, occasionally weather systems from remote origin cause significant disturbances. This study investigates the complex cloud-circulation interactions during the field campaign EUREC4A (Elucidate the Couplings Between Clouds, Convection and Circulation) from 16 January to 20 February 2020, using a combination of Eulerian and Lagrangian diagnostics. Based on observations and ERA5 reanalyses, we identify the relevant processes and characterize the formation pathways of two moist anomalies above the Barbados Cloud Observatory (BCO), one in the lower troposphere (~ 1000-650 hPa) and one in the middle troposphere (~ 650-300 hPa). These moist anomalies are associated with strongly negative CRE values and with contrasting long-range transport processes from the extratropics and the tropics, respectively. The first case study about the low-level moist anomaly is characterized by an unusually thick cloud layer, high precipitation totals, and a strongly negative CRE. The formation of the low-level moist anomaly is connected to an extratropical dry intrusion (EDI) that interacts with a trailing cold front. A quasi-climatological (2010-2020) analysis reveals that EDIs lead to different conditions at the BCO depending on how they interact with the associated trailing cold front. Based on this climatology, we discuss the relevance of the strong large-scale forcing by EDIs for the low-cloud patterns near the BCO and the related CRE. The second case study about the mid-tropospheric moist anomaly is associated with an extended and persistent mixed-phase shelf cloud and the lowest daily CRE value observed during the campaign. The formation of the mid-level moist anomaly is linked to "tropical mid-level detrainment"(TMD), which refers to detrainment from tropical deep convection near the melting layer. The quasi-climatological analysis shows that TMDs consistently lead to mid-tropospheric moist anomalies over the BCO and that the detrainment height controls the magnitude of the anomaly. However, no systematic relationship was found between the amplitude of this mid-tropospheric moist anomaly and the CRE at the BCO. This is most likely due to the modulation of the CRE by above and below lying clouds and the fact that we used daily mean CREs, thereby ignoring the impact of the timing of the synoptic anomaly with respect to the daily cycle. Overall, this study reveals the important impact of the long-range moisture transport, driven by dynamical processes either in the extratropics or the tropics, on the variability of the vertical structure of moisture and clouds, and on the resulting CRE in the North Atlantic winter trades

Tumour-derived leukaemia inhibitory factor is a major driver of cancer cachexia and morbidity in C26 tumour-bearing mice

BACKGROUND: Cancer cachexia is a metabolic wasting syndrome that is strongly associated with a poor prognosis. The initiating factors causing fat and muscle loss are largely unknown. Previously, we found that leukaemia inhibitory factor (LIF) secreted by C26 colon carcinoma cells was responsible for atrophy in treated myotubes. In the present study, we tested whether C26 tumour‐derived LIF is required for cancer cachexia in mice by knockout of Lif in C26 cells. METHODS: A C26 Lif null tumour cell line was made using CRISPR‐Cas9. Measurements of cachexia were compared in mice inoculated with C26 vs. C26^Lif−/− tumour cells, and atrophy was compared in myotubes treated with medium from C26 vs. C26^Lif−/− tumour cells. Levels of 25 cytokines/chemokines were compared in serum of mice bearing C26 vs. C26^Lif−/− tumours and in the medium from these tumour cell lines. RESULTS: At study endpoint, C26 mice showed outward signs of sickness while mice with C26^Lif−/− tumours appeared healthy. Mice with C26^Lif−/− tumours showed a 55–75% amelioration of body weight loss, muscle loss, fat loss, and splenomegaly compared with mice with C26 tumours (P < 0.05). The heart was not affected by LIF levels because the loss of cardiac mass was the same in C26 and C^26Lif−/− tumour‐bearing mice. LIF levels in mouse serum was entirely dependent on secretion from the tumour cells. Serum levels of interleukin‐6 and G‐CSF were increased by 79‐fold and 68‐fold, respectively, in C26 mice but only by five‐fold and two‐fold, respectively, in C26^Lif−/− mice, suggesting that interleukin‐6 and G‐CSF increases are dependent on tumour‐derived LIF. CONCLUSIONS: This study shows the first use of CRISPR‐Cas9 knockout of a candidate cachexia factor in tumour cells. The results provide direct evidence for LIF as a major cachexia initiating factor for the C26 tumour in vivo. Tumour‐derived LIF was also a regulator of multiple cytokines in C26 tumour cells and in C26 tumour‐bearing mice. The identification of tumour‐derived factors such as LIF that initiate the cachectic process is immediately applicable to the development of therapeutics to treat cachexia. This is a proof of principle for studies that when carried out in human cells, will make possible an understanding of the factors causing cachexia in a patient‐specific manner.This work was supported by NIAMS R01AR060217 to S. C. K. and R. W. J. and NIAMS R01 R01AR060209 to A. R. J., and by the Dudley Allen Sargent Research Fund. The authors certify that they comply with the ethical guidelines for publishing in the Journal of Cachexia, Sarcopenia and Muscle: update 2017.40 (R01AR060217 - NIAMS; R01 R01AR060209 - NIAMS; Dudley Allen Sargent Research Fund)Published versio

A Bio-Inspired Swellable Microneedle Adhesive for Mechanical Interlocking with Tissue

Achieving significant adhesion to soft tissues while minimizing tissue damage poses a considerable clinical challenge. Chemical-based adhesives require tissue-specific reactive chemistry, typically inducing a significant inflammatory response. Staples are fraught with limitations including high-localized tissue stress and increased risk of infection, and nerve and blood vessel damage. Here, inspired by the endoparasite Pomphorhynchus laevis which swells its proboscis to attach to its host’s intestinal wall, we have developed a biphasic microneedle array that mechanically interlocks with tissue through swellable microneedle tips, achieving ~ 3.5 fold increase in adhesion strength compared to staples in skin graft fixation, and removal force of ~ 4.5 N/cm2 from intestinal mucosal tissue. Comprising a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, conical microneedles penetrate tissue with minimal insertion force and depth, yet high adhesion strength in their swollen state. Uniquely, this design provides universal soft tissue adhesion with minimal damage, less traumatic removal, reduced risk of infection and delivery of bioactive therapeutics

SAPALDIA: Methods and participation in the cross-sectional part of the Swiss Study on Air Pollution and Lung Diseases in Adults

Summary: SAPALDIA-the Swiss Study on Air Pollution and Lung Diseases in Adults-focuses on the long term health effects of low to moderate levels of air pollutants as typically seen in different parts of Switzerland. The aim of the SAPALDIA cross-sectional study carried out in 1991 was to determine the prevalence of bronchial asthma, chronic bronchitis and allergic conditions in the adult population of Switzerland and to identify and to determine the respective importance of potentially influencing factors. These could be both personal (smoking habits, allergy status, family history, occupation) and environmental (outdoor and indoor pollution, aeroallergens, climate). A further aim of the cross-sectional study consisted in the identification of individuals susceptible to present symptoms during a two year observation period and to be included in the SAPALDIA follow-up study. This technical report represents the methodological documentation for the cross-sectional study of SAPALDIA. The instruments and the methods of standardisation are presented and discussed. The medical examination consisted of a computerised interview using a standardised questionnaire, the taking of a blood sample for serological tests, allergy skin testing, the measurement of endexpiratory CO and body height, and pulmonary function testing followed by methacholine challenge testing or bronchodilatation testing. The pattern of participation and the 9651 participants of the study, representing 59.3% of the sample, are described. Based on information on non-participants gained by telephone interviews and mailed short questionnaires, possible selection biases are quantified and discusse