A primary cilium, a sensory organelle present in almost every vertebrate cell, is regularly described in odontoblasts, projecting from the surfaces of the cells. Based on the hypothesis that the ...primary cilium is crucial both for dentin formation and possibly in tooth pain transmission, we have investigated the expression and localization of the main cilium components and involvement of the OFD1 gene in tooth morphogenesis. Odontoblasts in vitro express tubulin, inversin, rootletin, OFD1, BBS4, BBS6, ALMS1, KIF3A, PC1, and PC2. In vivo, cilia are aligned parallel to the dentin walls, with the top part oriented toward the pulp core. Close relationships between cilium and nerve fibers are evidenced. Calcium channels are concentrated in the vicinity of the basal body. Analysis of these data suggests a putative role of cilia in sensing the microenvironment, probably related to dentin secretion. This hypothesis is enhanced by the huge defects observed on molars from Ofd1 knockout mice, showing undifferentiated dentin-forming cells.
Virtual cancer care (i.e., teleoncology) was rapidly adopted during the COVID-19 pandemic to meet the needs of patients with cancer. However, there is a paucity of guidance for clinicians regarding ...virtual cancer care. We sought to develop consensus-based statements to guide the optimal provision of virtual care for clinicians caring for patients with cancer, using a modified Delphi consensus process with a 29-member panel consisting of an interprofessional group of clinicians caring for patients with cancer and patient representatives. The consensus process consisted of two rounds and one synchronous final consensus meeting. At the end of the modified Delphi process, 62 of 62 statements achieved consensus. Fifty-seven statements reached consensus in the first round of the process. Concerns regarding the ability to convey difficult news virtually and maintaining similar standards as in-person care without disproportionate strain on clinicians and patients were addressed in the consensus process. We achieved interprofessional consensus on virtual cancer care practices. Further research examining the impact of virtual cancer care on person-centred and clinical outcomes are needed to inform practices during the COVID-19 pandemic and beyond.
In the present article, we propose the perspective that abnormal glutamate homeostasis might contribute to diabetes pathogenesis. Previous reports and our recent data indicate that chronically high ...extracellular glutamate levels exert direct and indirect effects that might participate in the progressive loss of β-cells occurring in both T1D and T2D. In addition, abnormal glutamate homeostasis may impact all the three accelerators of the “accelerator hypothesis” and could partially explain the rising frequency of T1D and T2D.
In an accompanying paper du Preez et al., (2012) FEBS J279, 2810–2822, we adapt an existing kinetic model for steady‐state yeast glycolysis to simulate limit‐cycle oscillations. Here we validate the ...model by testing its capacity to simulate a wide range of experiments on dynamics of yeast glycolysis. In addition to its description of the oscillations of glycolytic intermediates in intact cells and the rapid synchronization observed when mixing out‐of‐phase oscillatory cell populations (see accompanying paper), the model was able to predict the Hopf bifurcation diagram with glucose as the bifurcation parameter (and one of the bifurcation points with cyanide as the bifurcation parameter), the glucose‐ and acetaldehyde‐driven forced oscillations, glucose and acetaldehyde quenching, and cell‐free extract oscillations (including complex oscillations and mixed‐mode oscillations). Thus, the model was compliant, at least qualitatively, with the majority of available experimental data for glycolytic oscillations in yeast. To our knowledge, this is the first time that a model for yeast glycolysis has been tested against such a wide variety of independent data sets.
Database
The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.biochem.sun.ac.za/database/dupreez/index.html.
We validate our model for limit cycle oscillations in yeast glycolysis by simulating a wide range of experiments and it is found to be compliant with the vast majority of data. To our knowledge this is the first time that such a model has been tested against such a wide variety of independent data sets not used for model construction
One of the main goals in flux-cored arc welding processes is the optimization of bead geometry, in which multiple geometric characteristics of the welding bead are important; therefore, ...multiobjective optimization programming is often applied. However, several optimization problems that use stochastic programming do not consider the impact of the correlation between the output variables on their probabilistic constraints. In this context, this paper aims to present a multiobjective optimization method based on multivariate stochastic programming. To demonstrate the applicability of the proposal, we conducted a design of experiments to optimize a flux-cored arc welding process for stainless-steel claddings. The weighting-sums method was applied to formulate the multiobjective optimization problem. It was possible to formulate a multivariate probability distribution for the penetration and dilution. In addition, a 95% probability to meet the predefined specification limits of the geometric characteristics was achieved.
An improved spectroscopy is used to implement and optimize the retrieval strategy of ethane (C2H6) from ground-based Fourier Transform Infrared (FTIR) solar spectra recorded at the high-altitude ...station of Jungfraujoch (Swiss Alps, 46.5°N, 8.0°E, 3580m a.s.l.). The improved spectroscopic parameters include C2H6 pseudo-lines in the 2720–3100cm−1 range and updated line parameters for methyl chloride and ozone. These improved spectroscopic parameters allow for substantial reduction of the fitting residuals as well as enhanced information content. They also contribute to limiting oscillations responsible for ungeophysical negative mixing ratio profiles. This strategy has been successfully applied to the Jungfraujoch solar spectra available from 1994 onwards. The resulting time series is compared with C2H6 total columns simulated by the state-of-the-art chemical transport model GEOS-Chem. Despite very consistent seasonal cycles between both data sets, a negative systematic bias relative to the FTIR observations suggests that C2H6 emissions are underestimated in the current inventories implemented in GEOS-Chem. Finally, C2H6 trends are derived from the FTIR time series, revealing a statistically-significant sharp increase of the C2H6 burden in the remote atmosphere above Jungfraujoch since 2009. Evaluating cause of this change in the C2H6 burden, which may be related to the recent massive growth of shale gas exploitation in North America, is of primary importance for atmospheric composition and air quality in the Northern Hemisphere.
•20-year time series of C2H6 is retrieved from ground-based FTIR solar spectra.•Improved spectroscopy reduces fitting residuals and enhances information content.•Negative bias to FTIR suggests underestimated C2H6 emissions in the GEOS-Chem model.•Trend analysis reveals a sharp increase of C2H6 burden since 2009.•C2H6 upturn may be related to growth of shale gas exploitation in North America.
Background
Atipamezole, an α‐2 adrenergic receptor antagonist, reverses the α‐2 agonist anesthetic effects. There is a dearth of information on the physiological effects of these drugs in cynomolgus ...macaques (Macaca fascicularis). We assessed atipamezole's physiologic effects. We hypothesized atipamezole administration would alter anesthetic parameters.
Methods
Five cynomolgus macaques were sedated with ketamine/dexmedetomidine intramuscularly, followed 45 min later with atipamezole (0.5 mg/kg). Anesthetic parameters (heart rate, blood pressure systolic (SAP), diastolic (DAP), and mean (MAP) blood pressure, body temperature, respiratory rate, and %SpO2) were monitored prior to and every 10 min (through 60 min) post atipamezole injection.
Results
While heart rate was significantly increased for 60 min; SAP, DAP, MAP, and temperature were significantly decreased at 10 min.
Conclusions
This study indicates subcutaneous atipamezole results in increased heart rate and transient blood pressure decrease. These findings are clinically important to ensure anesthetist awareness to properly support and treat patients as needed.
Extreme enhancements in the total columns of carbon monoxide (CO), peroxyacetyl nitrate (PAN), ethylene (C2H4), methanol (CH3OH), and formic acid (HCOOH) were observed over the Canadian high Arctic ...during the period of 17–22 August 2017 by a ground‐based Fourier transform infrared (FTIR) spectrometer at Eureka, Nunavut (80.05°N, 86.42°W), and by the Infrared Atmospheric Sounding Interferometer (IASI) satellite instruments. These enhancements have been attributed to wildfires in British Columbia (BC) and the Northwest Territories (NWT) of Canada, and represent the largest short‐term perturbations of PAN, C2H4, and HCOOH above ambient concentrations over the 14‐year (2006–2020) Eureka time‐series. Enhancement ratios, emission ratios, and emission factors relative to CO were calculated for all species for both FTIR and IASI observations. The C2H4 and HCOOH emission factors are significantly larger than previous studies, suggesting unusually high emissions from these fires. The wildfire plumes were also simulated using the GEOS‐Chem model. Initial GEOS‐Chem simulations displayed a severe under‐estimation relative to observations for these fire plumes resulting from the injection height scheme of the model. Sensitivity tests highlighted that injection heights of 12.5 km for BC (based on previous studies) and 10 km for the NWT fires yielded the strongest correlations with ground‐based measurements. Applying these injection heights to the model significantly improves the simulated plume transport and agreement with ground‐ and space‐based observations. GEOS‐Chem was also used to estimate the magnitude of secondary in‐plume production of CH3OH and HCOOH; it was found to be an important component (∼18%) of the enhanced HCOOH columns at Eureka.
Plain Language Summary
Wildfires are a significant natural source of pollution to the atmosphere. During mid‐August 2017, two extremely large wildfires occurred simultaneously in British Columbia (BC) and the Northwest Territories (NWT) of Canada. These fires produced an exceptional amount of smoke, which was subsequently transported to the Canadian high Arctic region. The atmospheric concentrations of carbon monoxide (CO), peroxyacetyl nitrate (PAN), ethylene (C2H4), methanol (CH3OH), and formic acid (HCOOH) contained within these transported smoke plumes were measured using both a ground‐based infrared spectrometer located at Eureka, Nunavut (80.05°N, 86.42°W) and satellite instruments. The largest concentrations of CO, PAN, C2H4, and HCOOH observed over the 14‐year measurement record (2006–2020) of the ground‐based spectrometer were due to these wildfires. The emissions of these fires were estimated from both the ground‐ and space‐based measurements and were found to be unusually high in comparison to previous studies. The wildfire smoke plumes were also simulated using a chemical transport model, but the model was found to inject the smoke too low into the atmosphere above the fires; after adjustments to the injection scheme were made, the agreement of the model with the measurements was significantly improved.
Key Points
The 2017 Canadian wildfires produced the largest PAN, C2H4, and HCOOH column enhancements observed in the high Arctic from 2006 to 2020
GEOS‐Chem effectively simulates the observed plume transport, but required modifications to the injection heights of the fire emissions
Mid‐latitude wildfires may become an increasingly significant source of reactive VOC species to the high Arctic during the summer months
This journal article explores Corporate Purpose as an approach to action the Sustainable Development Goals (SDGs). It achieves this objective by presenting a review of existing literature on ...Corporate Purpose and SDGs from the disciplines of business ethics, management studies, economics and psychology. The review showcases contributions exploring whether and how Corporate Purpose-led strategy facilitates the operationalization of the SDGs and proposes an emerging research agenda. This article employed an inductive approach methodology through grounded theory to develop a critical analysis of scientific evidence-based work for theory construction on Corporate Purpose. One of the major findings of this review is that to achieve the SDGs companies need to shift found from the “business as usual” approach, which perceives sustainability as an externality, to incorporating sustainability factors in the company’s underlying purpose. The article also (1) identifies trends in research outputs and reveals five major antecedents of the phenomenon (drivers to purpose), (2) identifies key gaps within the existing literature, (3) distinguishes three current approaches to Corporate Purpose and (4) elaborates on current theories of Corporate Purpose and SDGs linkages to identify opportunities and aid future research. In summary, this article unpacks Corporate Purpose mechanisms to action the SDGs and stimulates academic discussion of business transformational approaches to long-standing sustainability challenges.
Abstract Background/objectives The PROFUND index stratifies accurately the 12-month mortality risk of polypathological patients (PPs), but its fitness over a longer follow-up period remains unknown. ...We aimed to explore the calibration and discrimination power of PROFUND index over 4-years, in order to assess its follow-up interval generalizability. Design Multicenter prospective cohort-study. Setting 33 Spanish hospitals. Participants PPs included after hospital discharge, outpatient clinics, or home hospitalization. Measurements Mortality over a 4-year follow-up period. Methods PROFUND index calibration was assessed by risk-quartiles predicted/observed mortality (Hosmer–Lemeshow goodness-of-fit test), and its discrimination power by ROC curves. Results A total of 768 patients were included (630 82% of them completed the 4-year follow-up). Global mortality rate was 63.5%. When assessing individual patient scores, mortality was 52% in the lowest risk group (0–2 points in PROFUND score); 73.5% in the low-intermediate risk group (3–6 points), 85% in the intermediate-high group (7–10 points); and 92% in the highest risk group (≥ 11 points). Accuracy testing of the PROFUND index showed good calibration ( P = .8 in the Hosmer–Lemeshow goodness-of-fit test), and also a good discrimination power (AUC = 0.71 0.67–0.77 in ROC curve). Conclusions The PROFUND index maintained its accuracy in predicting mortality of polypathological patients over a 4-year follow-up period. This index may be of potential usefulness in deciding the most appropriate health-care interventions in populations with multimorbidity.