Mitochondrial dysfunction contributes to the senescent phenotype of IPF lung fibroblasts

Increasing evidence highlights that senescence plays an important role in idiopathic pulmonary fibrosis (IPF). This study delineates the specific contribution of mitochondria and the superoxide they form to the senescent phenotype of lung fibroblasts from IPF patients (IPF-LFs). Primary cultures of IPF-LFs exhibited an intensified DNA damage response (DDR) and were more senescent than age-matched fibroblasts from control donors (Ctrl-LFs). Furthermore, IPF-LFs exhibited mitochondrial dysfunction, exemplified by increases in mitochondrial superoxide, DNA, stress and activation of mTORC1. The DNA damaging agent etoposide elicited a DDR and augmented senescence in Ctrl-LFs, which were accompanied by disturbances in mitochondrial homoeostasis including heightened superoxide production. However, etoposide had no effect on IPF-LFs. Mitochondrial perturbation by rotenone involving sharp increases in superoxide production also evoked a DDR and senescence in Ctrl-LFs, but not IPF-LFs. Inhibition of mTORC1, antioxidant treatment and a mitochondrial targeting antioxidant decelerated IPF-LF senescence and/or attenuated pharmacologically induced Ctrl-LF senescence. In conclusion, increased superoxide production by dysfunctional mitochondria reinforces lung fibroblast senescence via prolongation of the DDR. As part of an auto-amplifying loop, mTORC1 is activated, altering mitochondrial homoeostasis and increasing superoxide production. Deeper understanding the mechanisms by which mitochondria contribute to fibroblast senescence in IPF has potentially important therapeutic implications

ISO Spectroscopy of Young Stellar Objects

Observations of gas-phase and solid-state species toward young stellar objects (YSOs) with the spectrometers on board the Infrared Space Observatory are reviewed. The excitation and abundances of the atoms and molecules are sensitive to the changing physical conditions during star-formation. In the cold outer envelopes around YSOs, interstellar ices contain a significant fraction of the heavy element abundances, in particular oxygen. Different ice phases can be distinguished, and evidence is found for heating and segregation of the ices in more evolved objects. The inner warm envelopes around YSOs are probed through absorption and emission of gas-phase molecules, including CO, CO_2, CH_4 and H_2O. An overview of the wealth of observations on gas-phase H_2O in star-forming regions is presented. Gas/solid ratios are determined, which provide information on the importance of gas-grain chemistry and high temperature gas-phase reactions. The line ratios of molecules such as H_2, CO and H_2O are powerful probes to constrain the physical parameters of the gas. Together with atomic and ionic lines such as [0 I] 63 µm, [S I] 25 µm and (Si II] 35 µm, they can also be used to distinguish between photon- and shock-heated gas. Finally, spectroscopic data on circumstellar disks around young stars are mentioned. The results are discussed in the context of the physical and chemical evolution of YSOs

A bacterial-based algorithm to simulate complex adaptive systems

Following a bacterial-based modeling approach, we want to model and analyze the impact of both decentralization and heterogeneity on group behavior and collective learning. Inspired by bacterial conjugation, we have defined an artificial society in which agents' strategies adapt to changes in resources location, allowing migration and survival in a dynamic sugarscape-like scenario. To study the impact of these variables we have simulated a scenario in which resources are limited and localized. We also have defined three constraints in genetic information processing (inhibition of plasmid conjugation, inhibition of plasmid reproduction and inhibition of plasmid mutation). Our results affirmed the hypothesis that efficiency of group adaptation to dynamic environments is better when societies are varied and distributed than when they are homogeneous and centralized

Modeling Life as Cognitive Info-Computation

This article presents a naturalist approach to cognition understood as a network of info-computational, autopoietic processes in living systems. It provides a conceptual framework for the unified view of cognition as evolved from the simplest to the most complex organisms, based on new empirical and theoretical results. It addresses three fundamental questions: what cognition is, how cognition works and what cognition does at different levels of complexity of living organisms. By explicating the info-computational character of cognition, its evolution, agent-dependency and generative mechanisms we can better understand its life-sustaining and life-propagating role. The info-computational approach contributes to rethinking cognition as a process of natural computation in living beings that can be applied for cognitive computation in artificial systems.Comment: Manuscript submitted to Computability in Europe CiE 201

Anatomic Optical Coherence Tomography (aOCT) for Evaluation of the Internal Nasal Valve

Objectives/Hypothesis: To establish the utility of anatomic optical coherence tomography (aOCT) in evaluating internal nasal valve (INV). Study Design: Anatomic specimen imaging study. Methods: Fresh-harvested human specimen heads were evaluated using both computed tomography (CT) imaging as well as using aOCT. Scans were performed at three time points: 1) After septoplasty for cartilage harvest, 2) after placement of butterfly graft (BFG), and 3) after placement of bilateral spreader grafts (SG). Imaging data were then converted into 3D models of the nasal airway. CT- and aOCT-generated models were compared by both static volumetric analysis and computational fluid dynamics (CFD) to predict nasal resistance and pressure. Results: Scans using aOCT showed comparable results to CT in terms of volumetric parameters both before and after intervention. Analysis of aOCT data by CFD demonstrated decrease in pressure after SG or BFG intervention. No statistically significant difference was observed when comparing CT- and aOCT-generated calculations of pressure or resistance. Conclusion: The INV can be imaged in a static fashion using aOCT technology. Advantages over traditional CT imaging include lack of exposure to radiation and rapid scan time. In addition, in-office use is possible as aOCT technology develops. Further investigation will be necessary to define the role of aOCT in the dynamic evaluation of this vital component of the nasal airway. Level of Evidence: III Laryngoscope, 2021

Cross-sectional survey of sexual health professionals’ experiences and perceptions of the 2022 mpox outbreak in the UK

Objective: To understand the experiences and perceptions of sexual health professionals responding to the May 2022 mpox outbreak in the UK. Design: Cross-sectional, anonymous, online survey collecting quantitative and qualitative data. Convenience sample recruited via an international network of sexual health and HIV clinicians responding to mpox and promoted through clinical associations and social media. Survey domains included: clinical workload; preparedness, support, and training; safety at work; vaccination; and well-being. Qualitative descriptive analysis of open-text responses was conducted to support interpretation of the quantitative data. Participants: Participants who were employed as sexual health professionals in the UK and had direct clinical experience of mpox were included in the analysis. The survey was completed between 11 August and 31 October 2022 by 139 respondents, the majority of whom were doctors (72.7%), cis-female (70.5%) and White (78.4%). Results: 70.3% reported that they were required to respond to mpox in addition to their existing clinical responsibilities, with 46.8% working longer hours as a result. In the open-text data, respondents highlighted that workload pressures were exacerbated by a lack of additional funding for mpox, pre-existing pressures on sexual health services, and unrealistic expectations around capacity. 67.6% of respondents reported experiencing negative emotional impact due to their mpox work, with stress (59.0%), fatigue (43.2%) and anxiety (36.0%) being the most common symptoms. 35.8% stated that they were less likely to remain in their profession because of their experiences during the mpox outbreak. In the open-text data, these feelings were ascribed to post-COVID exhaustion, understaffing and frustration among some participants at the handling of the mpox response. Conclusions: These findings indicate that sexual health services require increased funding and resources, along with evidence-based well-being interventions, to support sexual health professionals’ outbreak preparedness and recovery

Utility of endoscopic anatomical optical coherence tomography in functional rhinoplasty

Objective measurement of the nasal valve region is valuable for the assessment of functional rhinoplasty surgical outcomes. Anatomical optical coherence tomography (aOCT) is an imaging modality that may be used to obtain real-time, quantitative, and volumetric scans of the nasal airway. We aim to evaluate if volumetric aOCT imaging is useful for the examination of the nasal valve region before and after functional rhinoplasty procedures. aOCT scans of the nasal valves were performed on four cadaveric heads before and after spreader graft and butterfly graft procedures. The resulting aOCT images were compared against video endoscopy images, and the segmented volumes of the nasal airway obtained from aOCT scans were compared with computed tomography (CT) derived volumes acquired under the same conditions. The aOCT-derived volumes match the CT volumes closely, with a mean Dice similarity coefficient of 0.88 and a mean Hausdorff distance of 2.3 mm. Furthermore, the aOCT images were found to represent the shape of the nasal cavity accurately. Due to its ability to perform real-time, quantitative, and accurate evaluation of the nasal airway, aOCT imaging is a promising modality for the objective assessment of the nasal valves before and after functional rhinoplasty procedures

Results of the BiPo-1 prototype for radiopurity measurements for the SuperNEMO double beta decay source foils

The development of BiPo detectors is dedicated to the measurement of extremely high radiopurity in $^{208}$Tl and $^{214}$Bi for the SuperNEMO double beta decay source foils. A modular prototype, called BiPo-1, with 0.8 $m^2$ of sensitive surface area, has been running in the Modane Underground Laboratory since February, 2008. The goal of BiPo-1 is to measure the different components of the background and in particular the surface radiopurity of the plastic scintillators that make up the detector. The first phase of data collection has been dedicated to the measurement of the radiopurity in $^{208}$Tl. After more than one year of background measurement, a surface activity of the scintillators of $\mathcal{A}$($^{208}$Tl) $=$ 1.5 $\mu$Bq/m$^2$ is reported here. Given this level of background, a larger BiPo detector having 12 m$^2$ of active surface area, is able to qualify the radiopurity of the SuperNEMO selenium double beta decay foils with the required sensitivity of $\mathcal{A}$($^{208}$Tl) $<$ 2 $\mu$Bq/kg (90% C.L.) with a six month measurement.Comment: 24 pages, submitted to N.I.M.

Spectral modeling of scintillator for the NEMO-3 and SuperNEMO detectors

We have constructed a GEANT4-based detailed software model of photon transport in plastic scintillator blocks and have used it to study the NEMO-3 and SuperNEMO calorimeters employed in experiments designed to search for neutrinoless double beta decay. We compare our simulations to measurements using conversion electrons from a calibration source of $\rm ^{207}Bi$ and show that the agreement is improved if wavelength-dependent properties of the calorimeter are taken into account. In this article, we briefly describe our modeling approach and results of our studies.Comment: 16 pages, 10 figure