On the Importance of Atomic Fluctuations, Protein Flexibility, and Solvent in Ion Permeation

Proteins, including ion channels, often are described in terms of some average structure and pictured as rigid entities immersed in a featureless solvent continuum. This simplified view, which provides for a convenient representation of the protein's overall structure, incurs the risk of deemphasizing important features underlying protein function, such as thermal fluctuations in the atom positions and the discreteness of the solvent molecules. These factors become particularly important in the case of ion movement through narrow pores, where the magnitude of the thermal fluctuations may be comparable to the ion pore atom separations, such that the strength of the ion channel interactions may vary dramatically as a function of the instantaneous configuration of the ion and the surrounding protein and pore water. Descriptions of ion permeation through narrow pores, which employ static protein structures and a macroscopic continuum dielectric solvent, thus face fundamental difficulties. We illustrate this using simple model calculations based on the gramicidin A and KcsA potassium channels, which show that thermal atomic fluctuations lead to energy profiles that vary by tens of kcal/mol. Consequently, within the framework of a rigid pore model, ion-channel energetics is extremely sensitive to the choice of experimental structure and how the space-dependent dielectric constant is assigned. Given these observations, the significance of any description based on a rigid structure appears limited. Creating a conducting channel model from one single structure requires substantial and arbitrary engineering of the model parameters, making it difficult for such approaches to contribute to our understanding of ion permeation at a microscopic level

A multi-center study on the attitudes of Malaysian emergency health care staff towards allowing family presence during resuscitation of adult patients

BACKGROUND The practice of allowing family members to witness on-going active resuscitation has been gaining ground in many developed countries since it was first introduced in the early 1990s. In many Asian countries, the acceptability of this practice has not been well studied. AIM We conducted a multi-center questionnaire study to determine the attitudes of health care professionals in Malaysia towards family presence to witness ongoing medical procedures during resuscitation. METHODS Using a bilingual questionnaire (in Malay and English language), we asked our respondents about their attitudes towards allowing family presence (FP) as well as their actual experience of requests from families to be allowed to witness resuscitations. Multiple logistic regression was used to analyze the association between the many variables and a positive attitude towards FP. RESULTS Out of 300 health care professionals who received forms, 270 responded (a 90% response rate). Generally only 15.8% of our respondents agreed to allow relatives to witness resuscitations, although more than twice the number (38.5%) agreed that relatives do have a right to be around during resuscitation. Health care providers are significantly more likely to allow FP if the procedures are perceived as likely to be successful (e.g., intravenous cannulation and blood taking as compared to chest tube insertion). Doctors were more than twice as likely as paramedics to agree to FP (p-value = 0.002). This is probably due to the Malaysian work culture in our health care systems in which paramedics usually adopt a 'follow-the-leader' attitude in their daily practice. CONCLUSION The concept of allowing FP is not well accepted among our Malaysian health care providers

Suplemento mineral aniônico para vacas no periparto: parâmetros sanguíneos, urinários e incidência de patologias de importância na bovinocultura leiteira

A fim de avaliar o efeito do suplemento mineral aniônico sobre parâmetros sanguíneos, urinários e incidência de hipocalcemia e retenção de placenta, dezoito vacas de aptidão leiteira com grau de sangue 7/8 Holandesa preta e branca, com 440-620 kg e 5-10 anos, foram divididas com delineamento em blocos em função da ordem de parto em dois grupos: controle (BCAD=46,38mEq/kg de MS) e tratamento (com adição de suplemento mineral aniônico e BCAD = -249,28mEq/kg de MS). Foram monitorados níveis de cálcio total e pH na urina e soro sanguíneo; TCO2, pCO2, HCO3, excesso de base, cálcio ionizado, Na, K, Se no sangue; escore de condição corporal, hematócrito e hemoglobina. Os dados sanguíneos, urinários e ECC foram submetidos ao Proc Means do SAS (2000) com análise de variância a 5% e teste de Tukey e a incidência de retenção de placenta analisada por Mann-Whitney (P<0,07) e a concentração sérica de Se por teste t de Student (P<0,05), ambos pelo GraphPad Prism 5.0. O suplemento mineral aniônico diminuiu os valores de TCO2, pCO2, HCO3 e EB no sangue com menor perda de peso, mas a variação de pH e cálcio foi restrita ao tempo. O suplemento mineral aniônico não provocou leve acidose metabólica desejada e, consequentemente, não preveniu a hipocalcemia. Contudo, por apresentar Se em sua composição, proporcionou maior concentração deste micronutriente no soro e contribuiu para menor retenção de placenta

Open data from the third observing run of LIGO, Virgo, KAGRA, and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of binary black hole coalescences confidently observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include the effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that have already been identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total source-frame mass M > 70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz emitted gravitational-wave frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place a conservative upper limit for the merger rate density of high-mass binaries with eccentricities 0 < e ≤ 0.3 at 16.9 Gpc−3 yr−1 at the 90% confidence level

Open Data from the Third Observing Run of LIGO, Virgo, KAGRA, and GEO

Calibration of the LIGO strain data was performed with a GstLAL-based calibration software pipeline (Viets et al. 2018). Calibration of the Virgo strain data was performed with C-based software (Acernese et al. 2022b). Data quality products and event-validation results were computed using the DMT (https://labcit.ligo.caltech.edu/~jzweizig/DMT-Project. html), DQR (https://docs.ligo.org/detchar/data-quality-report/), DQSEGDB (Fisher et al. 2021), gwdetchar (Macloed et al. 2021a), hveto (Smith et al. 2011), iDQ (Essick et al. 2020), and Omicron (Robinet et al. 2020) software packages and contribut- ing software tools. Analyses relied upon the LALSuite software library (LIGO Scientific Collaboration 2018). PESummary was used to postprocess and collate parameter estimation results (Hoy & Raymond 2021). For an exhaustive list of the software used for searching the GW signals and characterizing their source, see Abbott et al. (2021c). Plots were prepared with Matplotlib (Hunter 2007), seaborn (Waskom 2021), GWSumm (Macleod et al. 2021b), and GWpy (Macleod et al. 2021c). NumPy (Harris et al. 2020) and SciPy (Virtanen et al. 2020) were used in the preparation of the manuscript. This material is based upon work supported by NSF’s LIGO Laboratory which is a major facility fully funded by the National Science Foundation. The authors also gratefully acknowledge the support of the Science and Technology Facilities Council (STFC) of the United Kingdom, the Max- Planck-Society (MPS), and the State of Niedersachsen/ Germany for support of the construction of Advanced LIGO and construction and operation of the GEO 600 detector. Additional support for Advanced LIGO was provided by the Australian Research Council. The authors gratefully acknowl- edge the Italian Istituto Nazionale di Fisica Nucleare (INFN), the French Centre National de la Recherche Scientifique (CNRS), and the Netherlands Organization for Scientific Research (NWO) for the construction and operation of the Virgo detector and the creation and support of the EGO consortium. The authors also gratefully acknowledge research support from these agencies as well as by the Council of Scientific and Industrial Research of India, the Department of Science and Technology, India, the Science & Engineering Research Board (SERB), India, the Ministry of Human Resource Development, India, the Spanish Agencia Estatal de Investigación (AEI), the Spanish Ministerio de Ciencia e Innovación and Ministerio de Universidades, the Conselleria de Fons Europeus, Universitat i Cultura and the Direcció General de Política Universitaria i Recerca del Govern de les Illes Balears, the Conselleria d'Innovació, Universitats, Ciència i Societat Digital de la Generalitat Valenciana and the CERCA Programme Generalitat de Catalunya, Spain, the National Science Centre of Poland and the European Union – European Regional Development Fund; Foundation for Polish Science (FNP), the Swiss National Science Foundation (SNSF), the Russian Foundation for Basic Research, the Russian Science Foundation, the European Commission, the European Social Funds (ESF), the European Regional Development Funds (ERDF), the Royal Society, the Scottish Funding Council, the Scottish Universities Physics Alliance, the Hungarian Scientific Research Fund (OTKA), the French Lyon Institute of Origins (LIO), the Belgian Fonds de la Recherche Scientifique (FRS- FNRS), Actions de Recherche Concertées (ARC) and Fonds Wetenschappelijk Onderzoek – Vlaanderen (FWO), Belgium, the Paris Île-de-France Region, the National Research, Development and Innovation Office Hungary (NKFIH), the National Research Foundation of Korea, the Natural Science and Engineering Research Council Canada, Canadian Founda- tion for Innovation (CFI), the Brazilian Ministry of Science, Technology, and Innovations, the International Center for Theoretical Physics South American Institute for Fundamental Research (ICTP-SAIFR), the Research Grants Council of Hong Kong, the National Natural Science Foundation of China (NSFC), the Leverhulme Trust, the Research Corporation, the Ministry of Science and Technology (MOST), Taiwan, the United States Department of Energy, and the Kavli Foundation. The authors gratefully acknowledge the support of the NSF, STFC, INFN, and CNRS for provision of computational resources. This work was supported by MEXT, JSPS Leading-edge Research Infrastructure Program, JSPS Grant-in-Aid for Specially Promoted Research 26000005, JSPS Grant-in-Aid for Scientific Research on Innovative Areas 2905: JP17H06358, JP17H06361 and JP17H06364, JSPS Core-to- Core Program A, Advanced Research Networks, JSPS Grant- in-Aid for Scientific Research (S) 17H06133 and 20H05639, JSPS Grant-in-Aid for Transformative Research Areas (A) 20A203: JP20H05854, the joint research program of the Institute for Cosmic Ray Research, University of Tokyo, National Research Foundation (NRF), Computing Infrastruc- ture Project of Global Science experimental Data hub Center (GSDC) at KISTI, Korea Astronomy and Space Science Institute (KASI), and Ministry of Science and ICT (MSIT) in Korea, Academia Sinica (AS), AS Grid Center (ASGC) and the National Science and Technology Council (NSTC) in Taiwan under grants including the Rising Star Program and Science Vanguard Research Program, Advanced Technology Center (ATC) of NAOJ, and Mechanical Engineering Center of KEK.Peer reviewe

Ion movement through gramicidin A channels. Interfacial polarization effects on single-channel current measurements

Gramicidin A single-channel current-voltage characteristics were studied at low permeant ion concentrations and very high applied potentials. The purpose of these experiments was to elucidate the basis for the small, but definite, voltage dependence observed under these circumstances. It was found that this residual voltage dependence is a reflection of interfacial polarization effects, similar to those proposed by Walz et al. (Biophys. J. 9:1150–1159). It will be concluded that there exists an effectively voltage-independent step in the association reaction between a gramicidin A channel and the permeating ion. Some consequences of interfacial polarization effects for the analysis of conductance vs. activity relations will be discussed