Endogenous chloride channels of insect sf9 cells. Evidence for coordinated activity of small elementary channel units

The endogenous Cl- conductance of Spodoptera frugiperda (Sf9) cells was studied 20-35 h after plating out of either uninfected cells or cells infected by a baculovirus vector carrying the cloned beta-galactosidase gene (beta-Gal cells). With the cation Tris+ in the pipette and Na+ in the bath, the reversal potential of whole-cell currents was governed by the prevailing Cl- equilibrium potential and could be fitted by the Goldman-Hodgkin-Katz equation with similar permeabilities for uninfected and beta-Gal cells. In the frequency range 0.12 < f < 300 Hz, the power density spectrum of whole-cell Cl- currents could be fitted by three Lorentzians. Independent of membrane potential, >50% of the total variance of whole-cell current fluctuations was accounted for by the low frequency Lorentzian (fc = 0.40 +/- 0.03 Hz, n = 6). Single-Cl- channels showed complex gating kinetics with long lasting (seconds) openings interrupted by similar long closures. In the open state, channels exhibited fast burst-like closures. Since the patches normally contained more than a single channel, it was not possible to measure open and closed dwell-time distributions for comparing single-Cl- channel activity with the kinetic features of whole-cell currents. However, the power density spectrum of Cl- currents of cell-attached and excised outside-out patches contained both high and low frequency Lorentzian components, with the corner frequency of the slow component (fc = 0.40 +/- 0.02 Hz, n = 4) similar to that of whole-cell current fluctuations. Chloride channels exhibited multiple conductance states with similar Goldman-Hodgkin-Katz-type rectification. Single-channel permeabilities covered the range from approximately 0.6.10(-14) cm5/s to approximately 6.10(-14) cm3/s, corresponding to a limiting conductance (gamma 150/150) of approximately 3.5 pS and approximately 35 pS, respectively. All states reversed near the same membrane potential, and they exhibited similar halide ion selectivity, P1 > PCl approximately PBr. Accordingly, Cl- current amplitudes larger than current flow through the smallest channel unit resolved seem to result from simultaneous open/shut events of two or more channel units

Analysis of 83mKr prompt scintillation signals in the PIXeY detector

Prompt scintillation signals from 83mKr calibration sources are a useful metric to calibrate the spatial variation of light collection efficiency and electric field magnitude of a two phase liquid-gas xenon time projection chamber. Because 83mKr decays in two steps, there are two prompt scintillation pulses for each calibration event, denoted S1a and S1b. We study the ratio of S1b to S1a signal sizes in the Particle Identification in Xenon at Yale (PIXeY) experiment and its dependence on the time separation between the two signals (Δ t), notably its increase at low Δ t. In PIXeY data, the Δ t dependence of S1b/S1a is observed to exhibit two exponential components: one with a time constant of 0.05 ± 0.02 μ s, which can be attributed to processing effects and pulse overlap and one with a time constant of 10.2 ± 2.2 μs that increases in amplitude with electric drift field, the origin of which is not yet understood

Serosurvey of Coxiella burnetii (Q fever) in Dromedary Camels (Camelus dromedarius) in Laikipia County, Kenya

Dromedary camels (Camelus dromedarius) are an important protein source for people in semi-arid and arid regions of Africa. In Kenya, camel populations have grown dramatically in the past few decades resulting in the potential for increased disease transmission between humans and camels. An estimated four million Kenyans drink unpasteurized camel milk, which poses a disease risk. We evaluated the seroprevalence of a significant zoonotic pathogen, Coxiella burnetii (Q fever), among 334 camels from nine herds in Laikipia County, Kenya. Serum testing revealed 18.6% positive seroprevalence of Coxiella burnetii (n = 344). Increasing camel age was positively associated with C. burnetii seroprevalence (OR = 5.36). Our study confirmed that camels living in Laikipia County, Kenya, have been exposed to the zoonotic pathogen, C. burnetii. Further research to evaluate the role of camels in disease transmission to other livestock, wildlife and humans in Kenya should be conducted

Association of osteoarthritis risk factors with knee and hip pain in a population-based sample of 29-59 year olds in Denmark: a cross-sectional analysis.

BACKGROUND: This study aimed to a) describe the prevalence of knee and hip osteoarthritis risk factors in a population of 29-59 year old individuals, b) estimate the association between persistent knee/hip pain and osteoarthritis risk factors, and c) describe the prevalence of osteoarthritis risk factors, including specific biomechanical risk factors, in individuals with prolonged persistent knee or hip pain. METHODS: Participants completed the "Early Detection and Prevention" pilot study questionnaire, including items on presence of knee/hip pain within the last month and osteoarthritis risk factors. Individuals reporting knee/hip problems completed a second questionnaire, including items about most problematic joint and specific biomechanical osteoarthritis risk factors. After describing the prevalence of persistent knee/hip pain and osteoarthritis risk factors among respondents stratified for sex and age, logistic regression was used to estimate the strength of associations between osteoarthritis risk factors and presence of knee/hip pain. The prevalence of prolonged persistent pain (i.e. knee/hip pain reported at both questionnaires) and osteoarthritis risk factors among respondents with prolonged persistent knee and hip pain, were described. RESULTS: Two thousand six hundred sixty-one respondents completed the first survey. The one-month prevalence of persistent knee/hip pain was 27%. Previous knee/hip injury was associated with persistent knee/hip pain for both sexes in all age groups, while a family history of osteoarthritis was associated with persistent knee/hip pain in all age groups except for 29-39 year old men. A higher BMI was associated with persistent knee/hip pain in 40-59 year old women, and 50-59 year old men. Eight hundred sixty seven respondents completed the second questionnaire. Knee/hip injuries and surgeries were more common in individuals with prolonged persistent knee than hip pain. CONCLUSIONS: Knee/hip pain within the last month was frequent among individuals aged 29-59 years. Multiple known osteoarthritis risk factors were associated with presence of knee/hip pain. Joint injury and previous surgery were more common in individuals with knee than hip pain. The results support the notion that joint injury and overweight during early adulthood are signs of a trajectory towards symptomatic osteoarthritis later in life and may help earlier identification of groups at high risk of future symptomatic osteoarthritis. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02797392 ). Registered April 29,2016

A 2-year prospective study of patient-relevant outcomes in patients operated on for knee osteoarthritis with tibial osteotomy

BACKGROUND: Tibial osteotomy is a treatment for younger and/or physically active patients suffering from uni-compartmental knee osteoarthritis. The open wedge osteotomy by the hemicallotasis technique includes the use of external fixation. The use of external fixation has several advantages, as early mobilization and the opportunity for optimal correction. However, the hemicallotasis technique has also been described as a cumbersome procedure for the patient. The aim of this study was to prospectively evaluate patient-relevant outcomes during the first 2 post-operative years. Especially the treatment period, during which external fixation was used, was closely monitored. METHODS: In an uncontrolled study, fifty-eight consecutive patients, 30 men and 28 women (mean age 54 years) were operated on by the hemicallotasis technique were evaluated with the patient-relevant outcome measure Knee injury and Osteoarthritis Outcome Score (KOOS) preoperatively, during the treatment with external fixation, one week after removal of the external fixation, at 6 months, and at one and two years postoperatively. RESULTS: At the 2-year postoperative follow-up, all subscales of the KOOS were improved (p < 0.001), mostly in pain (41–80 on a 0–100 worst to best scale) and knee-related quality of life (21–61 on a 0–100 worst to best scale), compared to the preoperative status. Significant improvements in pain and other symptoms, function of daily life and quality of life were seen already during the treatment period (mean 98 ± 18 days) with the external fixation. More demanding functions such as kneeling, squatting, jumping and running, were improved first after extraction of the external fixation device and the pins. CONCLUSION: Tibial osteotomy by the hemicallotasis technique yields large improvement in self-rated pain, function and quality of life, which persists over two years. Surprisingly, large improvements occurred already during the immediate post-operative period when the external fixation was still used

Local delivery of novel MRTF/SRF inhibitors prevents scar tissue formation in a preclinical model of fibrosis

The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway represents a promising therapeutic target to prevent fibrosis. We have tested the effects of new pharmacological inhibitors of MRTF/SRF signalling in a preclinical model of fibrosis. CCG-222740, a novel MRTF/SRF inhibitor, markedly decreased SRF reporter gene activity and showed a greater inhibitory effect on MRTF/SRF target genes than the previously described MRTF-A inhibitor CCG-203971. CCG-222740 was also five times more potent, with an IC50 of 5 μM, in a fibroblast-mediated collagen contraction assay, was less cytotoxic, and a more potent inhibitor of alpha-smooth muscle actin protein expression than CCG-203971. Local delivery of CCG-222740 and CCG-203971 in a validated and clinically relevant rabbit model of scar tissue formation after glaucoma filtration surgery increased the long-term success of the surgery by 67% (P < 0.0005) and 33% (P < 0.01), respectively, and significantly decreased fibrosis and scarring histologically. Unlike mitomycin-C, neither CCG-222740 nor CCG-203971 caused any detectable epithelial toxicity or systemic side effects with very low drug levels measured in the aqueous, vitreous, and serum. We conclude that inhibitors of MRTF/SRF-regulated gene transcription such as CCG-222740, potentially represent a new therapeutic strategy to prevent scar tissue formation in the eye and other tissues

When are prime formulae characteristic?

In the setting of the modal logic that characterizes modal refinement over modal transition systems, Boudol and Larsen showed that the formulae for which model checking can be reduced to preorder checking, that is, the characteristic formulae, are exactly the consistent and prime ones. This paper presents general, sufficient conditions guaranteeing that characteristic formulae are exactly the consistent and prime ones. It is shown that the given conditions apply to the logics characterizing all the semantics in van Glabbeek's branching-time spectrum

The beta-Oslo method: experimentally constrained (n,γn,\gamma) reaction rates relevant to the rr-process

Unknown neutron-capture reaction rates remain a significant source of uncertainty in state-of-the-art $r$-process nucleosynthesis reaction network calculations. As the $r$-process involves highly neutron-rich nuclei for which direct ($n,\gamma$) cross-section measurements are virtually impossible, indirect methods are called for to constrain ($n,\gamma$) cross sections used as input for the $r$-process nuclear network. Here we discuss the newly developed beta-Oslo method, which is capable of providing experimental input for calculating ($n,\gamma$) rates of neutron-rich nuclei. The beta-Oslo method represents a first step towards constraining neutron-capture rates of importance to the $r$-process.Comment: 4 pages, 1 figure, conference proceedings Nuclei in the Cosmos XV 2018, Italy

The quantitative verification benchmark set

We present an extensive collection of quantitative models to facilitate the development, comparison, and benchmarking of new verification algorithms and tools. All models have a formal semantics in terms of extensions of Markov chains, are provided in the Jani format, and are documented by a comprehensive set of metadata. The collection is highly diverse: it includes established probabilistic verification and planning benchmarks, industrial case studies, models of biological systems, dynamic fault trees, and Petri net examples, all originally specified in a variety of modelling languages. It archives detailed tool performance data for each model, enabling immediate comparisons between tools and among tool versions over time. The collection is easy to access via a client-side web application at qcomp.org with powerful search and visualisation features. It can be extended via a Git-based submission process, and is openly accessible according to the terms of the CC-BY license