From single-molecule spectroscopy to super-resolution imaging of the neuron: a review.

For more than 20 years, single-molecule spectroscopy has been providing invaluable insights into nature at the molecular level. The field has received a powerful boost with the development of the technique into super-resolution imaging methods, ca. 10 years ago, which overcome the limitations imposed by optical diffraction. Today, single molecule super-resolution imaging is routinely used in the study of macromolecular function and structure in the cell. Concomitantly, computational methods have been developed that provide information on numbers and positions of molecules at the nanometer-scale. In this overview, we outline the technical developments that have led to the emergence of localization microscopy techniques from single-molecule spectroscopy. We then provide a comprehensive review on the application of the technique in the field of neuroscience research.This work was supported by grants from the UK Engineering and Physical Sciences Research Council (EPSRC), The Wellcome Trust, Alzheimer’s Research UK, the Medical Research Council (MRC), and the Biotechnology and Biological Sciences Resesarch Council (BBSRC)

Trace anomaly driven inflation

This paper investigates Starobinsky's model of inflation driven by the trace anomaly of conformally coupled matter fields. This model does not suffer from the problem of contrived initial conditions that occurs in most models of inflation driven by a scalar field. The universe can be nucleated semi-classically by a cosmological instanton that is much larger than the Planck scale provided there are sufficiently many matter fields. There are two cosmological instantons: the four sphere and a new ``double bubble'' solution. This paper considers a universe nucleated by the four sphere. The AdS/CFT correspondence is used to calculate the correlation function for scalar and tensor metric perturbations during the ensuing de Sitter phase. The analytic structure of the scalar and tensor propagators is discussed in detail. Observational constraints on the model are discussed. Quantum loops of matter fields are shown to strongly suppress short scale metric perturbations, which implies that short distance modifications of gravity would probably not be observable in the cosmic microwave background. This is probably true for any model of inflation provided there are sufficiently many matter fields. This point is illustrated by a comparison of anomaly driven inflation in four dimensions and in a Randall-Sundrum brane-world model.Comment: LaTeX, 42 pages, 5 .eps figures. v2: typos corrected, references added and 2 new paragraphs in conclusions section. v3: comments about strong coupling and unboundedness of action changed, other minor changes. v4: Comments about strong coupling changed again (2-point functions of metric perturbations do not depend on Yang-Mills coupling

Connected pathway relative permeability from pore-scale imaging of imbibition

Pore-scale images obtained from a synchrotron-based X-ray computed micro-tomography (µCT) imbibition experiment in sandstone rock were used to conduct Navier–Stokes flow simulations on the connected pathways of water and oil phases. The resulting relative permeability was compared with steady-state Darcy-scale imbibition experiments on 5 cm large twin samples from the same outcrop sandstone material. While the relative permeability curves display a large degree of similarity, the endpoint saturations for the µCT data are 10% in saturation units higher than the experimental data. However, the two datasets match well when normalizing to the mobile saturation range. The agreement is particularly good at low water saturations, where the oil is predominantly connected. Apart from different saturation endpoints, in this particular experiment where connected pathway flow dominates, the discrepancies between pore-scale connected pathway flow simulations and Darcy-scale steady-state data are minor overall and have very little impact on fractional flow. The results also indicate that if the pore-scale fluid distributions are available and the amount of disconnected non-wetting phase is low, quasi-static flow simulations may be sufficient to compute relative permeability. When pore-scale fluid distributions are not available, fluid distributions can be obtained from a morphological approach, which approximates capillary-dominated displacement. The relative permeability obtained from the morphological approach compare well to drainage steady state whereas major discrepancies to the imbibition steady-state experimental data are observed. The morphological approach does not represent the imbibition process very well and experimental data for the spatial arrangement of the phases are required. Presumably for modeling imbibition relative permeability an approach is needed that captures moving liquid-liquid interfaces, which requires viscous and capillary forces simultaneously

Accidental Inflation in String Theory

We show that inflation in type IIB string theory driven by the volume modulus can be realized in the context of the racetrack-based Kallosh-Linde model (KL) of moduli stabilization. Inflation here arises through the volume modulus slow-rolling down from a flat hill-top or inflection point of the scalar potential. This situation can be quite generic in the landscape, where by uplifting one of the two adjacent minima one can turn the barrier either to a flat saddle point or to an inflection point supporting eternal inflation. The resulting spectral index is tunable in the range of 0.93 < n_s < 1, and there is only negligible production of primordial gravitational waves r < 10^{-6}. The flatness of the potential in this scenario requires fine-tuning, which may be justified taking into account the exponential reward by volume factors preferring the regions of the universe with the maximal amount of slow-roll inflation. This consideration leads to a tentative prediction of the spectral index $n_s\approx 0.95$ or $n_s \approx 0.93$ depending on whether the potential has a symmetry phi -> - phi or not.Comment: 15 pages, 6 figures, LaTeX, uses RevTex

KEYLINK: Towards a more integrative soil representation for inclusion in ecosystem scale models - II: Model description, implementation and testing

New knowledge on soil structure highlights its importance for hydrology and soil organic matter (SOM) stabilization, which however remains neglected in many wide used models. We present here a new model, KEYLINK, in which soil structure is integrated with the existing concepts on SOM pools, and elements from food web models, that is, those from direct trophic interactions among soil organisms. KEYLINK is, therefore, an attempt to integrate soil functional diversity and food webs in predictions of soil carbon (C) and soil water balances. We present a selection of equations that can be used for most models as well as basic parameter intervals, for example, key pools, functional groups' biomasses and growth rates. Parameter distributions can be determined with Bayesian calibration, and here an example is presented for food web growth rate parameters for a pine forest in Belgium. We show how these added equations can improve the functioning of the model in describing known phenomena. For this, five test cases are given as simulation examples: changing the input litter quality (recalcitrance and carbon to nitrogen ratio), excluding predators, increasing pH and changing initial soil porosity. These results overall show how KEYLINK is able to simulate the known effects of these parameters and can simulate the linked effects of biopore formation, hydrology and aggregation on soil functioning. Furthermore, the results show an important trophic cascade effect of predation on the complete C cycle with repercussions on the soil structure as ecosystem engineers are predated, and on SOM turnover when predation on fungivore and bacterivore populations are reduced. In summary, KEYLINK shows how soil functional diversity and trophic organization and their role in C and water cycling in soils should be considered in order to improve our predictions on C sequestration and C emissions from soils. © 2021 PeerJ Inc.. All rights reserved.The following grant information was disclosed by the authors: COST (European Cooperation in Science and Technology): FP1305 (BioLink) and ES1406 (KEYSOM). Short Term Scientific Mission (STSM) programs. Spanish Ministry of Science, Innovation and Universities. Spanish Ministry of Economy and Competitiveness (MINECO): IBERYCA (CGL2017-84723-P). BC3 María de Maeztu Excellence Accreditation: MDM-2017-0714. Basque Government: BERC 2018-2021. This article is based upon work from COST Actions FP1305 (BioLink) and ES1406 (KEYSOM), supported by COST (European Cooperation in Science and Technology), and their Short Term Scientific Mission (STSM) programs. Omar Flores’ work was funded by FPU PhD grant program of the Spanish Ministry of Science, Innovation and Universities. Jorge Curiel Yuste received funding from the Spanish Ministry of Economy and Competitiveness (MINECO) under projects IBERYCA (CGL2017-84723-P) and the BC3 María de Maeztu excellence accreditation (MDM-2017-0714). Jorge Curiel Yuste also received funding from the Basque Government through the BERC 2018-2021 program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Antihypertensive drug concentration measurement combined with personalized feedback in resistant hypertension:a randomized controlled trial

Background:Adherence to antihypertensive drugs (AHDs) is crucial for controlling blood pressure (BP). We aimed to determine the effectiveness of measuring AHD concentrations using a dried blood spot (DBS) sampling method to identify nonadherence, combined with personalized feedback, in reducing resistant hypertension.Methods:We conducted a multicenter, randomized, controlled trial (RHYME-RCT, ICTRP NTR6914) in patients with established resistant hypertension. Patients were randomized to receive either an intervention with standard of care (SoC) or SoC alone. SoC consisted of BP measurement and DBS sampling at baseline, 3 months (t3), 6 months (t6), and 12 months (t12); AHD concentrations were measured but not reported in this arm. In the intervention arm, results on AHD concentrations were discussed during a personalized feedback conversation at baseline and t3. Study endpoints included the proportion of patients with RH and AHD adherence at t12.Results:Forty-nine patients were randomized to receive the intervention+SoC, and 51 were randomized to receive SoC alone. The proportion of adherent patients improved from 70.0 to 92.5% in the intervention+SoC arm (P = 0.008, n = 40) and remained the same in the SoC arm (71.4%, n = 42). The difference in adherence between the arms was statistically significant (P = 0.014). The prevalence of resistant hypertension decreased to 75.0% in the intervention+SoC arm (P &lt; 0.001, n = 40) and 59.5% in the SoC arm (P &lt; 0.001, n = 42) at t12; the difference between the arms was statistically nonsignificant (P = 0.14).Conclusion:Personalized feedback conversations based on DBS-derived AHD concentrations improved AHD adherence but did not reduce the prevalence of RH.</p

EP-1179: What the gamma? The correlation between QA and clinical risk estimates for prostate RapidArc plans

Influenza virus infection can be accompanied by life-threatening immune pathology most likely due to excessive antiviral responses. Inhibitory immune receptors may restrain such overactive immune responses. To study the role of the inhibitory immune receptor CD200R and its ligand CD200 during influenza infection, we challenged wild-type and CD200(-/-) mice with influenza virus. We found that CD200(-/-) mice in comparison to wild-type controls when inoculated with influenza virus developed more severe disease, associated with increased lung infiltration and lung endothelium damage. CD200(-/-) mice did develop adequate adaptive immune responses and were able to control viral load, suggesting that the severe disease was caused by a lack of control of the immune response. Interestingly, development of disease was completely prevented by depletion of T cells before infection, despite dramatically increased viral load, indicating that T cells are essential for the development of disease symptoms. Our data show that lack of CD200-CD200R signaling increases immune pathology during influenza infection, which can be reduced by T cell depletion. The Journal of Immunology, 2009, 183: 1990-1996