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1.
Biosens Bioelectron ; 262: 116546, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38968774

ABSTRACT

Electronic communication in natural systems makes use, inter alia, of molecular transmission, where electron transfer occurs within networks of redox reactions, which play a vital role in many physiological systems. In view of the limited understanding of redox signaling, we developed an approach and an electrochemical-optical lab-on-a-chip to observe cellular responses in localized redox environments. The developed fluidic micro-system uses electrogenetic bacteria in which a cellular response is activated to electrically and chemically induced stimulations. Specifically, controlled environments for the cells are created by using microelectrodes to generate spatiotemporal redox gradients. The in-situ cellular responses at both single-cell and population levels are monitored by optical microscopy. The elicited electrogenetic fluorescence intensities after 210 min in response to electrochemical and chemical activation were 1.3 × 108±0.30 × 108 arbitrary units (A.U.) and 1.2 × 108±0.30 × 108 A.U. per cell population, respectively, and 1.05 ± 0.01 A.U. and 1.05 ± 0.01 A.U. per-cell, respectively. We demonstrated that redox molecules' mass transfer between the electrode and cells - and not the applied electrical field - activated the electrogenetic cells. Specifically, we found an oriented amplified electrogenetic response on the charged electrodes' downstream side, which was determined by the location of the stimulating electrodes and the flow profile. We then focused on the cellular responses and observed distinct subpopulations that were attributed to electrochemical rather than chemical stimulation, with the distance between the cells and the stimulating electrode being the main determinant. These observations provide a comprehensive understanding of the mechanisms by which diffusible redox mediators serve as electron shuttles, imposing context and activating electrogenetic responses.


Subject(s)
Biosensing Techniques , Oxidation-Reduction , Biosensing Techniques/methods , Single-Cell Analysis/methods , Lab-On-A-Chip Devices , Microelectrodes , Electrochemical Techniques/methods , Equipment Design , Electron Transport
2.
Phys Chem Chem Phys ; 26(28): 19117-19129, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38957118

ABSTRACT

Ru is a metal of interest in catalysis. Monodisperse Ru3 clusters as catalytic sites are relevant for the development of catalysts because clusters use significantly lower amounts of precious materials for forming active sites due to the small size of the cluster. However, retaining the mono-dispersity of the cluster size after deposition is a challenge because surface energy could drive both agglomeration and encapsulation of the clusters. In the present work Ru3 clusters are deposited by chemical vapor deposition (CVD) of Ru3(CO)12 and cluster source depositions of bare Ru3 onto radio frequency sputter-deposited TiO2 (RF-TiO2) substrates, TiO2(100), and SiO2. When supported on RF-TiO2, bare Ru3 is encapsulated by a layer of titania substrate material during deposition with a cluster source. Ligated Ru3(CO)12 is also encapsulated by a layer of titania when deposited onto sputter-treated RF-TiO2, but only through heat treatment which is required to remove most of the ligands. The titania overlayer thickness was determined to be 1-2 monolayers for Ru3(CO)12 clusters on RF-TiO2, which is thin enough for catalytic or photocatalytic reactions to potentially occur even without clusters being part of the very outermost layer. The implication for catalysis of the encapsulation of Ru3 into the RF-TiO2 is discussed. Temperature-dependent X-ray photoelectron spectroscopy (XPS), angle-resolved XPS, and temperature-dependent low energy ion scattering (TD-LEIS) are used to probe how the cluster-surface interaction changes due to heat treatment and scanning transmission electron microscopy (STEM) was used to image the depth of the surface from side-on.

3.
Anal Chem ; 96(28): 11343-11352, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38973712

ABSTRACT

Modern research faces increasingly complex materials with a constant need for new analytical strategies that can provide deeper levels of chemical insight. Ultrahigh resolution mass spectrometry (MS), particularly Fourier transform ion cyclotron resonance (FTICR) MS, has provided a robust analytical foundation. However, MS alone offers limited structural information. Here, we present the first implementation and results from an FTICR MS with fully integrated dual accumulation analysis with gated trapped ion mobility spectrometry (gTIMS) capability. The drastically extended charge capacity and parallel accumulation facilitate the analysis of complex mixtures. We achieved a high dynamic range of 4 orders of magnitude within a single FTICR acquisition event. Simultaneously, the valuable linear relationship between the TIMS elution voltage and reduced mobility was retained over a wide mobility range. Benchmarking the instrument performance with Suwannee River fulvic acid (SRFA) by variable ramp gTIMS analysis allowed separation and unambiguous assignment of different charge state distributions. Application to bio-oils has proven the capability to distinguish the isomeric diversity in these ultracomplex samples, while maintaining the expected FTICR MS resolving power and mass accuracy. Valuable information about the molecular distribution, isomeric diversity, and main molecular differences could directly be extracted within the analysis time of a classical "dilute and shoot" direct infusion experiment. The development of this fully integrated and flexible gTIMS with FTICR MS analysis possesses the potential to significantly change the current landscape of high-resolution mass spectrometric analysis of complex mixtures through the added insight of isomeric complexity afforded by TIMS. The exploration of the added IMS dimension promises transformative effects across diverse fields including energy transition, environmental studies, and biological research.

4.
Nature ; 630(8018): 976-983, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38867048

ABSTRACT

Interleukin (IL-)23 is a major mediator and therapeutic target in chronic inflammatory diseases that also elicits tissue protection in the intestine at homeostasis or following acute infection1-4. However, the mechanisms that shape these beneficial versus pathological outcomes remain poorly understood. To address this gap in knowledge, we performed single-cell RNA sequencing on all IL-23 receptor-expressing cells in the intestine and their acute response to IL-23, revealing a dominance of T cells and group 3 innate lymphoid cells (ILC3s). Unexpectedly, we identified potent upregulation of the immunoregulatory checkpoint molecule cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) on ILC3s. This pathway was activated by gut microbes and IL-23 in a FOXO1- and STAT3-dependent manner. Mice lacking CTLA-4 on ILC3s exhibited reduced regulatory T cells, elevated inflammatory T cells and more-severe intestinal inflammation. IL-23 induction of CTLA-4+ ILC3s was necessary and sufficient to reduce co-stimulatory molecules and increase PD-L1 bioavailability on intestinal myeloid cells. Finally, human ILC3s upregulated CTLA-4 in response to IL-23 or gut inflammation and correlated with immunoregulation in inflammatory bowel disease. These results reveal ILC3-intrinsic CTLA-4 as an essential checkpoint that restrains the pathological outcomes of IL-23, suggesting that disruption of these lymphocytes, which occurs in inflammatory bowel disease5-7, contributes to chronic inflammation.


Subject(s)
Immunity, Innate , Inflammation , Interleukin-23 , Lymphocytes , Animals , Female , Humans , Male , Mice , CTLA-4 Antigen/metabolism , Forkhead Box Protein O1/metabolism , Forkhead Box Protein O1/genetics , Gastrointestinal Microbiome , Inflammation/immunology , Inflammation/pathology , Inflammation/metabolism , Interleukin-23/immunology , Intestines/immunology , Intestines/pathology , Lymphocytes/immunology , Lymphocytes/metabolism , Mice, Inbred C57BL , Myeloid Cells/metabolism , Single-Cell Gene Expression Analysis , STAT3 Transcription Factor/metabolism , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism
5.
ACS Energy Lett ; 9(6): 2492-2499, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38911534

ABSTRACT

Silicon's potential as a lithium-ion battery (LIB) anode is hindered by the reactivity of the lithium silicide (Li x Si) interface. This study introduces an innovative approach by alloying silicon with boron, creating boron/silicon (BSi) nanoparticles synthesized via plasma-enhanced chemical vapor deposition. These nanoparticles exhibit altered electronic structures as evidenced by optical, structural, and chemical analysis. Integrated into LIB anodes, BSi demonstrates outstanding cycle stability, surpassing 1000 lithiation and delithiation cycles with minimal capacity fade or impedance growth. Detailed electrochemical and microscopic characterization reveal very little SEI growth through 1000 cycles, which suggests that electrolyte degradation is virtually nonexistent. This unconventional strategy offers a promising avenue for high-performance LIB anodes with the potential for rapid scale-up, marking a significant advancement in silicon anode technology.

6.
Front Integr Neurosci ; 18: 1364249, 2024.
Article in English | MEDLINE | ID: mdl-38721469

ABSTRACT

Introduction: Over the last decade of research, a notable connection between autism spectrum disorder (ASD) and unique motor system characteristics has been identified, which may influence social communication through distinct movement patterns. In this study, we investigated the potential for features of the broader autism phenotype to account for kinematic idiosyncrasies in social movements expressed by neurotypical individuals. Methods: Fifty-eight participants provided recordings of point-light displays expressing three basic emotions and completed the Autism Spectrum Quotient (AQ). We extracted kinematic metrics from the biological movements using computer vision and applied linear mixed-effects modeling to analyze the relationship between these kinematic metrics and AQ scores. Results: Our results revealed that individual differences in the total AQ scores, and the sub-scale scores, significantly predicted variations in kinematic metrics representing order, volume, and magnitude. Discussion: The results of this study suggest that autistic traits may intricately influence the movement expressions at the microlevel, highlighting the need for a more nuanced understanding of the potential endophenotypic characteristics associated with social movements in neurotypical individuals.

7.
Physiother Can ; 76(2): 232-235, 2024 May.
Article in English | MEDLINE | ID: mdl-38725595

ABSTRACT

Purpose: The Objective Structured Clinical Examination (OSCE) and station examinations, in general, have been widely utilized in health professional programmes to evaluate students' clinical performance prior to advancing to a clinical placement. The COVID-19 pandemic impacted student preparation and implementation of our programme's OSCEs. The impact on changes in student OSCE performance due COVID-19 has not been well studied. This non-concurrent cohort study evaluated the difference before and during COVID-19 pandemic on Year 1 physiotherapy students' performances on an in-person OSCE by estimating the mean difference in cohort OSCE scores and safety occurrences. Methods: Two cohorts of MSc (PT) students were compared: Cohort A (not impacted by COVID-19) and Cohort B (impacted by COVID-19). Cohort scores were summarized as means and 95% CIs. Results: Overall OSCE scores for Cohort A and B were 77.9 and 81.9, respectively (d¯ = 4.0, 95% CI: 2.1, 5.8). Cohort B students were approximately 4 times more likely to demonstrate safety occurrences. Conclusion: The impact of COVID-19 did not adversely affect total OSCE scores; however, it did increase safety infractions.


Objectif: en général, les programmes pour les professionnels de la santé font largement appel à l'examen clinique objectif structuré (ECOS) et aux stations d'examen pour évaluer la performance clinique des étudiants avant leur passage au stage clinique. La pandémie de COVID-19 a nui à la préparation des étudiants et à la mise en œuvre des ECOS du programme de physiothérapie. Les effets sur les changements à la performance des étudiants à l'ECOS découlant de la COVID-19 n'ont pas été bien étudiés. La présente étude de cohorte non concomitante a permis d'évaluer la différence entre la performance des étudiants en première année de physiothérapie à un ECOS en personne avant et pendant la pandémie de COVID-19, d'après la différence moyenne des scores d'ECOS et des occurrences d'infractions aux règles de sécurité au sein des deux cohortes. Méthodologie: deux cohortes d'étudiants à la maîtrise en physiothérapie ont été comparées : la cohorte A (non touchée par la COVID-19) et B (touchée par la COVID-19). Les scores des cohortes ont été résumés sous forme de moyennes et d'IC à 95%. Résultats: les scores globaux de l'ECOS pour la cohorte A et la cohorte B s'élevaient à 77,9 et à 81,9, respectivement (d¯ = 4,0, IC à 95 % : 2,1, 5,8). Les étudiants de la cohorte B étaient environ quatre fois plus susceptibles de démontrer des occurrences d'infraction aux règles de sécurité. Conclusion: la COVID-19 n'a pas nui aux scores totaux de l'ECOS, mais les infractions aux règles de sécurité se sont accrues.

8.
Schizophr Res ; 269: 71-78, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38749320

ABSTRACT

One-third of people with schizophrenia have elevated levels of anti-gliadin antibodies (AGA IgG). A 5-week randomized double-blind pilot study was performed in 2014-2017 in an inpatient setting to test the effect of a gluten-free diet (GFD) on participants with schizophrenia or schizoaffective disorder who also had elevated AGA IgG (≥ 20 U) but were negative for celiac disease. This earlier pilot study reported that the GFD-group showed improved gastrointestinal and psychiatric symptoms, and also improvements in TNF-α and the inflammatory cytokine IL-23. Here, we performed measurements of these banked plasma samples to detect levels of oxidative stress (OxSt) using a recently developed iridium (Ir)-reducing capacity assay. Triplicate measurements of these samples showed an Intraclass Correlation Coefficient of 0.84 which indicates good reproducibility. Further, a comparison of the OxSt measurements at the baseline and 5-week end-point for this small sample size shows that the GFD-group (N = 7) had lowered OxSt levels compared to the gluten-containing diet group (GCD; N = 9; p = 0.05). Finally, we showed that improvements in OxSt over these 5 weeks were correlated to improvements in gastrointestinal (r = +0.64, p = 0.0073) and psychiatric (r = +0.52, p = 0.039) symptoms. Also, we showed a possible association between the decrease in OxSt and the lowered levels of IL-23 (r = +0.44, p = 0.087), although without statistical significance. Thus, the Ir-reducing capacity assay provides a simple, objective measure of OxSt with the results providing further evidence that inflammation, redox dysregulation and OxSt may mediate interactions between the gut and brain.


Subject(s)
Diet, Gluten-Free , Oxidative Stress , Schizophrenia , Humans , Schizophrenia/diet therapy , Schizophrenia/blood , Pilot Projects , Oxidative Stress/physiology , Male , Adult , Female , Middle Aged , Double-Blind Method , Psychotic Disorders/diet therapy , Psychotic Disorders/blood , Psychotic Disorders/immunology , Gliadin/immunology
9.
J Neurol Sci ; 461: 123041, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38744216

ABSTRACT

Inflammatory central nervous system (CNS) diseases, such as multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), are characterized by humoral immune abnormalities. Anti-MOG antibodies are not specific to MOGAD, with their presence described in MS. Autoantibodies may also be present and play a role in various neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease driven by motor neuron dysfunction. While immune involvement in ALS has been recognized, the presence of antibodies targeting CNS myelin antigens has not been established. We aimed to establish a live cell-based assay for quantification of serum anti-MOG IgG1 in patients with CNS diseases, including MS and ALS. In total, 771 serum samples from the John L. Trotter MS Center and the Northeast ALS Consortium were examined using a live cell-based assay for detection of anti-MOG IgG1. Samples from three cohorts were tested in blinded fashion: healthy control (HC) subjects, patients with clinically diagnosed MOGAD, and an experimental group of ALS and MS patients. All samples from established MOGAD cases were positive for anti-MOG antibodies, while all HC samples were negative. Anti-MOG IgG1 was detected in 65 of 658 samples (9.9%) from MS subjects and 4 of 108 (3.7%) samples from ALS subjects. The presence of serum anti-MOG IgG1 in MS and ALS patients raises questions about the contribution of these antibodies to disease pathophysiology as well as accuracy of diagnostic approaches for CNS inflammatory diseases.


Subject(s)
Amyotrophic Lateral Sclerosis , Autoantibodies , Immunoglobulin G , Myelin-Oligodendrocyte Glycoprotein , Myelin-Oligodendrocyte Glycoprotein/immunology , Humans , Autoantibodies/blood , Female , Male , Middle Aged , Amyotrophic Lateral Sclerosis/blood , Amyotrophic Lateral Sclerosis/immunology , Amyotrophic Lateral Sclerosis/diagnosis , Immunoglobulin G/blood , Neurodegenerative Diseases/immunology , Neurodegenerative Diseases/blood , Neurodegenerative Diseases/diagnosis , Aged , Neuroinflammatory Diseases/immunology , Neuroinflammatory Diseases/blood , Adult , Multiple Sclerosis/immunology , Multiple Sclerosis/blood , Animals
10.
Circ Arrhythm Electrophysiol ; 17(6): e012635, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38804141

ABSTRACT

BACKGROUND: Irrigated radiofrequency ablation with half-normal saline can potentially increase lesion size but may increase the risk of steam pops with the risk of emboli or perforation. We hypothesized that pops would be preceded by intracardiac echocardiography (ICE) findings as well as a large impedance fall. METHODS: In 100 consecutive patients undergoing endocardial ventricular arrhythmia radiofrequency ablation with half-normal saline, we attempted to observe the ablation site with ICE. Radiofrequency ablation power was titrated to a 15 to 20 Ohm impedance fall and could be adjusted for tissue whitening and increasing bubble formation on ICE. Steam pops were defined as audible or a sudden explosion of microbubbles on ICE. RESULTS: Of 2190 ablation applications in 100 patients (82% cardiomyopathy, 50% sustained ventricular tachycardia), pops occurred during 43 (2.0%) applications. Sites with pops had greater impedance decreases of 18 [14, 21]% versus 13 [10, 17]% (P<0.001). ICE visualized 1308 (59.7%) radiofrequency sites, and fewer pops occurred when ICE visualized the radiofrequency ablation site (1.4%) compared with without ICE visualization (2.8%; P=0.016). Of the 18 ICE-visible pops, 7 (39%) were silent but recognized as an explosion of bubbles on ICE. With ICE, 89% of pops were preceded by either tissue whitening or a sudden increase in bubbles. In a multivariable model, tissue whitening and a sudden increase in bubbles were associated with steam pops (odds ratio, 7.186; P=0.004, and odds ratio, 29.93; P<0.001, respectively), independent of impedance fall and power. There were no pericardial effusions or embolic events with steam pops. CONCLUSIONS: Steam pops occurred in 2% of half-normal saline radiofrequency applications titrated to an impedance fall and are likely under-recognized without ICE. On ICE, steam pops are usually preceded by tissue whitening or a sudden increase in bubble formation, which can potentially be used to adjust radiofrequency application to help reduce pops.


Subject(s)
Catheter Ablation , Echocardiography , Saline Solution , Steam , Tachycardia, Ventricular , Therapeutic Irrigation , Humans , Male , Female , Saline Solution/administration & dosage , Middle Aged , Catheter Ablation/adverse effects , Tachycardia, Ventricular/surgery , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/diagnostic imaging , Aged , Embolism, Air/prevention & control , Embolism, Air/etiology , Embolism, Air/diagnostic imaging , Treatment Outcome , Risk Factors , Predictive Value of Tests , Electric Impedance
11.
Childs Nerv Syst ; 40(8): 2333-2344, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38702518

ABSTRACT

INTRODUCTION: Focused ultrasound (FUS) is an innovative and emerging technology for the treatment of adult and pediatric brain tumors and illustrates the intersection of various specialized fields, including neurosurgery, neuro-oncology, radiation oncology, and biomedical engineering. OBJECTIVE: The authors provide a comprehensive overview of the application and implications of FUS in treating pediatric brain tumors, with a special focus on pediatric low-grade gliomas (pLGGs) and the evolving landscape of this technology and its clinical utility. METHODS: The fundamental principles of FUS include its ability to induce thermal ablation or enhance drug delivery through transient blood-brain barrier (BBB) disruption, emphasizing the adaptability of high-intensity focused ultrasound (HIFU) and low-intensity focused ultrasound (LIFU) applications. RESULTS: Several ongoing clinical trials explore the potential of FUS in offering alternative therapeutic strategies for pathologies where conventional treatments fall short, specifically centrally-located benign CNS tumors and diffuse intrinsic pontine glioma (DIPG). A case illustration involving the use of HIFU for pilocytic astrocytoma is presented. CONCLUSION: Discussions regarding future applications of FUS for the treatment of gliomas include improved drug delivery, immunomodulation, radiosensitization, and other technological advancements.


Subject(s)
Brain Neoplasms , Humans , Brain Neoplasms/therapy , Brain Neoplasms/diagnostic imaging , Child , Glioma/therapy , Glioma/diagnostic imaging , Ultrasonic Therapy/methods
12.
Phys Chem Chem Phys ; 26(21): 15547-15558, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38756091

ABSTRACT

Polycyclic aromatic nitrogen heterocycles (PANHs) are present in various astronomical environments where they are subjected to intense radiation. Their photodissociation pathways give crucial insights into the cycle of matter in the universe, yet so far only the dissociation characteristics of few PANHs have been investigated. Moreover, most experiments use single photon techniques that only reveal the initial dissociation step, and are thus unsuited to replicate astronomical environments and timescales. In this work, we use the Instrument for the Photodynamics of PAHs (i-PoP) at the Laboratory for Astrophysics to simulate the interstellar photodissociation of a model PANH, cationic triazacoronene (TAC˙+, C21H9N3). Comparing the observed fragments to similar PAHs such as the isoelectronic coronene can give mechanistic insight into PAH dissociation. For coronene the major photodissociation products were found to be C9H+, C10+, and C11+. In contrast, fragmentation in TAC˙+ is initiated by up to three HCN losses often in combination with H- or H2 losses. In the lower mass region, the fragments show similarities to comparable PAHs like coronene, but for TAC˙+ the inclusion of nitrogen atoms into the ionic fragments in the form of e.g. (di)cyanopolyynes is also observed. These nitrogen-containing species may be important tracers of regions in interstellar space where interstellar PANHs are being photodissociated.

13.
Contemp Clin Trials ; 143: 107584, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38821260

ABSTRACT

BACKGROUND: Pilot trials indicate that both a low glycemic load (GL) diet and calorie restriction (CR) can be implemented successfully in people with multiple sclerosis (pMS) and may improve MS symptoms and physical function, but large randomized clinical trials (RCTs) have not yet been conducted. The purpose of this study is to test these interventions alone and in combination to determine their efficacy for improving clinical and patient reported outcomes (PROs) in pMS. METHODS: This 32-week, two-arm, RCT at two centers will randomly assign 100 adults with relapsing-remitting or secondary progressive MS to a low GL diet (n = 50) or a standard GL diet (n = 50). Both diet groups will complete two study phases: a eucaloric phase (16 weeks) and a CR phase (16 weeks). Groceries for the study meal plans will be delivered to participants' homes weekly. The primary outcome is physical function, measured by timed 25-ft walk test. Secondary outcomes are pain, fatigue, mood, and anxiety. DISCUSSION: This will be the most rigorous intervention trial to date of a low GL diet and CR in adults with MS, and among the first to assess the impact of intentional weight loss on MS symptoms. Results will provide valuable insight for recommending dietary change, weight loss, or both to adults with MS. These non-drug interventions pose few risks and have potential to yield significant improvements in MS symptoms. TRIAL REGISTRATION ID: NCT05327322.

14.
Article in English | MEDLINE | ID: mdl-38805611

ABSTRACT

BACKGROUND: The early identification of outbreaks of both known and novel influenza-like illnesses is an important public health problem. OBJECTIVE: The design and testing of a tool that detects and tracks outbreaks of both known and novel influenza-like illness, such as the SARS-CoV-19 worldwide pandemic, accurately and early. METHODS: This paper describes the ILI Tracker algorithm that first models the daily occurrence of a set of known influenza-like illnesses in hospital emergency departments in a monitored region using findings extracted from patient care reports using natural language processing. We then show how the algorithm can be extended to detect and track the presence of an unmodeled disease which may represent a novel disease outbreak. RESULTS: We include results based on modeling the diseases influenza, respiratory syncytial virus, human metapneumovirus, and parainfluenza for five emergency departments in Allegheny County Pennsylvania from June 1, 2014 through May 31, 2015. We also include the results of detecting the outbreak of an unmodeled disease, which in retrospect was very likely an outbreak of the enterovirus EV-D68. CONCLUSIONS: The results reported in this paper provide support that ILI Tracker was able to track well the incidence of four modeled influenza-like diseases over a one-year period, relative to laboratory confirmed cases, and it was computationally efficient in doing so. The system was alsoable to detect a likely novel outbreak of the enterovirus D68 early in an outbreak that occurred in Allegheny County in 2014, as well as clinically characterize that outbreak disease accurately.

15.
Proc Natl Acad Sci U S A ; 121(20): e2215679121, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38709924

ABSTRACT

Limiting the rise in global temperature to 1.5 °C will rely, in part, on technologies to remove CO2 from the atmosphere. However, many carbon dioxide removal (CDR) technologies are in the early stages of development, and there is limited data to inform predictions of their future adoption. Here, we present an approach to model adoption of early-stage technologies such as CDR and apply it to direct air carbon capture and storage (DACCS). Our approach combines empirical data on historical technology analogs and early adoption indicators to model a range of feasible growth pathways. We use these pathways as inputs to an integrated assessment model (the Global Change Analysis Model, GCAM) and evaluate their effects under an emissions policy to limit end-of-century temperature change to 1.5 °C. Adoption varies widely across analogs, which share different strategic similarities with DACCS. If DACCS growth mirrors high-growth analogs (e.g., solar photovoltaics), it can reach up to 4.9 GtCO2 removal by midcentury, compared to as low as 0.2 GtCO2 for low-growth analogs (e.g., natural gas pipelines). For these slower growing analogs, unabated fossil fuel generation in 2050 is reduced by 44% compared to high-growth analogs, with implications for energy investments and stranded assets. Residual emissions at the end of the century are also substantially lower (by up to 43% and 34% in transportation and industry) under lower DACCS scenarios. The large variation in growth rates observed for different analogs can also point to policy takeaways for enabling DACCS.

16.
Phys Chem Chem Phys ; 26(20): 14970-14979, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38739372

ABSTRACT

Curcumin is a medicinal agent that exhibits anti-cancer and anti-Alzheimer's disease properties. It has a keto-enol moiety that gives rise to many of its chemical properties including metal complexation and acid-base equilibria. A previous study has shown that keto-enol tautomerization at this moiety is implicated in the anti-Alzheimer's disease effect of curcumin, highlighting the importance of this process. In this study, tautomerization of curcumin in methanol, acetone and acetonitrile was investigated using time-resolved 1H nuclear magnetic resonance spectroscopy. Curcumin undergoes hydrogen-deuterium exchange with the solvents and the proton resonance peak corresponding to the hydrogen at the α-carbon position (Cα) decays as a function of time, signifying deuteration at this position. Because tautomerization is the rate limiting step in the deuteration of curcumin at the Cα position, the rate of tautomerization is inferred from the rate of deuteration. The rate constant of tautomerization of curcumin shows a temperature dependence and analysis using the Arrhenius equation revealed activation energies (Ea) of tautomerization of (80.1 ± 5.9), (64.1 ± 1.0) and (68.3 ± 5.5) kJ mol-1 in methanol, D2O/acetone and D2O/acetonitrile, respectively. Insight into the role of water in tautomerization of curcumin was further offered by density functional theory studies. The transition state of tautomerization was optimized in the presence of water molecules. The results show a hydrogen-bonded solvent bridge between the diketo moiety and Cα of curcumin. The Ea of tautomerization of curcumin shows a strong dependence on the number of water molecules in the solvent bridge, indicating the critical role played by the solvent bridge in catalyzing tautomerization of curcumin.


Subject(s)
Curcumin , Curcumin/chemistry , Methanol/chemistry , Acetonitriles/chemistry , Acetone/chemistry , Isomerism , Thermodynamics , Solvents/chemistry
17.
Europace ; 26(4)2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38587017

ABSTRACT

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society, the Asia Pacific Heart Rhythm Society, and the Latin American Heart Rhythm Society .


Subject(s)
Atrial Fibrillation , Catheter Ablation , Humans , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Latin America , Treatment Outcome , Catheters , Asia , Catheter Ablation/adverse effects , Catheter Ablation/methods
18.
Article in English | MEDLINE | ID: mdl-38609733

ABSTRACT

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society (HRS), the Asia Pacific HRS, and the Latin American HRS.

19.
Sci Rep ; 14(1): 9666, 2024 04 26.
Article in English | MEDLINE | ID: mdl-38671069

ABSTRACT

Redox is a unique, programmable modality capable of bridging communication between biology and electronics. Previous studies have shown that the E. coli redox-responsive OxyRS regulon can be re-wired to accept electrochemically generated hydrogen peroxide (H2O2) as an inducer of gene expression. Here we report that the redox-active phenolic plant signaling molecule acetosyringone (AS) can also induce gene expression from the OxyRS regulon. AS must be oxidized, however, as the reduced state present under normal conditions cannot induce gene expression. Thus, AS serves as a "pro-signaling molecule" that can be activated by its oxidation-in our case by application of oxidizing potential to an electrode. We show that the OxyRS regulon is not induced electrochemically if the imposed electrode potential is in the mid-physiological range. Electronically sliding the applied potential to either oxidative or reductive extremes induces this regulon but through different mechanisms: reduction of O2 to form H2O2 or oxidation of AS. Fundamentally, this work reinforces the emerging concept that redox signaling depends more on molecular activities than molecular structure. From an applications perspective, the creation of an electronically programmed "pro-signal" dramatically expands the toolbox for electronic control of biological responses in microbes, including in complex environments, cell-based materials, and biomanufacturing.


Subject(s)
Escherichia coli , Oxidation-Reduction , Signal Transduction , Escherichia coli/genetics , Escherichia coli/metabolism , Hydrogen Peroxide , Regulon/genetics , Gene Expression Regulation, Bacterial , Escherichia coli Proteins/metabolism , Escherichia coli Proteins/genetics , Phenols/chemistry , Phenols/metabolism
20.
J Acoust Soc Am ; 155(4): 2724-2727, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38656337

ABSTRACT

The auditory sensitivity of a small songbird, the red-cheeked cordon bleu, was measured using the standard methods of animal psychophysics. Hearing in cordon bleus is similar to other small passerines with best hearing in the frequency region from 2 to 4 kHz and sensitivity declining at the rate of about 10 dB/octave below 2 kHz and about 35 dB/octave as frequency increases from 4 to 9 kHz. While critical ratios are similar to other songbirds, the long-term average power spectrum of cordon bleu song falls above the frequency of best hearing in this species.


Subject(s)
Acoustic Stimulation , Auditory Threshold , Hearing , Songbirds , Vocalization, Animal , Animals , Vocalization, Animal/physiology , Hearing/physiology , Songbirds/physiology , Male , Psychoacoustics , Sound Spectrography , Female
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