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1.
Chem Sci ; 15(27): 10359-10365, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38994411

RESUMO

Carbon-carbon (C-C) bond formation is a cornerstone of synthetic chemistry, relying on routes such as transition-metal mediated cross-coupling for the introduction of new carbon-based functionality. For {[M] n+-C} (M = metal) structural units, studies that offer well-defined relationships between metal oxidation state, hydrocarbon strain, and {[M] n+-C} bond thermochemistry are thus informative, providing a means to reliably access new product classes. Here, we show that one-electron oxidation of the iron tucked-in complex [(η6-C5Me4[double bond, length as m-dash]CH2)Fe(dnppe)] (dnppe = 1,2-bis(di-n-propylphosphino)ethane) results in C(sp3)-C(sp3) bond formation giving unique {Fe2} dimers. Freeze-quenched CW X-band EPR spectroscopy allowed for spectroscopic identification of the reactive [(η6-C5Me4[double bond, length as m-dash]CH2)Fe(dnppe)]+ intermediate. Density functional theory (DFT) calculations reveal a primarily Fe-centered radical and a weak {[Fe]-C} bond (BDE[Fe]-C = 24.5 kcal mol-1, c.f. BDEC-C(ethane) = 90 kcal mol-1). For comparison, a structurally analogous Fe(iii) methyl complex was prepared, [Cp*Fe(dnppe)(CH3)]+ (Cp* = C5Me5 -), where C(sp3)-C(sp3) coupling was not observed, consistent with a larger calculated BDE[Fe]-C value of 47.8 kcal mol-1. These data are analogized to the simple hydrocarbons ethane and cyclopropane, where a strain-induced BDEC-C decrease of 33 kcal mol-1 is witnessed on cyclization.

2.
Addict Biol ; 29(7): e13419, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38949209

RESUMO

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions. These goals are achieved by: (A) using innovative mHealth (mobile health) tools to longitudinally monitor the effects of triggers and modifying factors on drug consumption patterns in real life in a cohort of 900 patients with alcohol use disorder. This approach will be complemented by animal models of addiction with 24/7 automated behavioural monitoring across an entire disease trajectory; i.e. from a naïve state to a drug-taking state to an addiction or resilience-like state. (B) The identification and, if applicable, computational modelling of key molecular, neurobiological and psychological mechanisms (e.g., reduced cognitive flexibility) mediating the effects of such triggers and modifying factors on disease trajectories. (C) Developing and testing non-invasive interventions (e.g., Just-In-Time-Adaptive-Interventions (JITAIs), various non-invasive brain stimulations (NIBS), individualized physical activity) that specifically target the underlying mechanisms for regaining control over drug intake. Here, we will report on the most important results of the first funding period and outline our future research strategy.


Assuntos
Transtornos Relacionados ao Uso de Substâncias , Humanos , Animais , Alemanha , Comportamento Aditivo , Alcoolismo
3.
Dalton Trans ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976284

RESUMO

The use of metal catalysts to accelerate an organic transformation has proven indispensable for access to structural motifs having applications across medicinal, polymer, materials chemistry, and more. Most catalytic approaches have cast transition metals in the "leading role"; these players mediate important reactions such as C-C cross coupling and the hydrogenation of unsaturated bonds. These catalysts may require collaboration, featuring Lewis acidic or basic additives to promote a desired reaction outcome. Lewis acids can serve to accelerate reactions by way of substrate stabilization and/or activation, and as such, are valuable in optimizing catalytic transformations. A burgeoning area of chemical research which unifies these concepts has thus sought to develop transition metal complexes having ambiphilic (containing a Lewis basic and acidic unit) ligands. This approach takes advantage of metal-ligand cooperativity to increase the efficiency of a given chemical transformation, leveraging intramolecular interactions between a transition metal and an adjacent secondary ligand site. While this has shown significant potential to facilitate challenging and important transformations, there remains unexplored depth for creativity and future advancement. This Frontier highlights inter- and intramolecular combinations of transition metals and Lewis acids that together, provide a collaborative platform for chemical synthesis.

4.
Chem Commun (Camb) ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888889

RESUMO

Whereas κ3-P,C,P-based donor ligands are ubiquitous across synthetic chemistry, related unsymmetric systems having κ3-P,P,C-coordination are comparatively rare. In this contribution, we expose a new κ3-P,P,C ligand system, bearing a C3-anionic linker and its coordination chemistry with iridium. The title ligand has been coordinated in saturated and unsaturated forms. The degree of ligand saturation affected an onward (and unusual) oxidative rearrangement reaction.

5.
Lung ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935158

RESUMO

PURPOSE: This study aimed to evaluate the hypothesis that active smoking impacts upon mediators and abundance of circulating fibrocyte cells in smoking-related disease characterised by fibrosis. METHODS: Flow cytometry and enzyme-linked immunosorbent assays were used to investigate blood from five patient groups: healthy never-smokers, healthy current smokers, stable chronic obstructive pulmonary disease (COPD) active smokers, idiopathic pulmonary fibrosis (IPF) never-smokers, and IPF active smokers. RESULTS: A significant inverse dose-response relationship was observed in healthy smokers among cumulative smoking burden (pack-years) and fibrocyte abundance (p = 0.006, r = -0.86). Among serum profibrotic fibrocyte chemokines measured, CCL18 rose significantly alongside fibrocyte numbers in all five subject groups, while having an inverse dose-response relationship with pack-year burden in healthy smokers (p = 0.003, r = -0.89). In IPF, CCL2 rose in direct proportion to fibrocyte abundance irrespective of smoking status but had lower serum levels in those currently smoking (p = < 0.001). For the study population, CXCL12 was decreased in pooled current smokers versus never-smokers (p = 0.03). CONCLUSION: The suppressive effect of current, as distinct from former, chronic smoking on circulating fibrocyte abundance in healthy smokers, and modulation of regulatory chemokine levels by active smoking may have implications for future studies of fibrocytes in smoking-related lung diseases as a potential confounding variable.

6.
Oncologist ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869252

RESUMO

BACKGROUND: Chemotherapy-induced alopecia is a common consequence of cancer treatment with a high psychological impact on patients and can be prevented by scalp cooling (SC). With this multi-center patient series, we examined the results for multiple currently used chemotherapy regimens to offer an audit into the real-world determinants of SC efficacy. MATERIALS AND METHODS: The Dutch Scalp Cooling Registry collected data on 7424 scalp-cooled patients in 68 Dutch hospitals. Nurses and patients completed questionnaires on patient characteristics, chemotherapy, and SC protocol. Patient-reported primary outcomes at the start of the final SC session included head cover (HC) (eg, wig/scarf) use (yes/no) as a surrogate for patient satisfaction with SC and WHO score for alopecia (0 = no hair loss up to 3 = total alopecia) as a measure of scalp cooling success. Exhaustive logistic regression analysis stratified by chemotherapy regimen was implemented to examine characteristics and interactions associated with the SC result. RESULTS: Overall, over half of patients (n = 4191, 56%) did not wear a HC and 53% (n = 3784/7183) reported minimal hair loss (WHO score 0/1) at the start of their final treatment. Outcomes were drug and dose dependent. Besides the chemotherapy regimen, this study did not identify any patient characteristic or lifestyle factor as a generic determinant influencing SC success. For non-gender specific cancers, gender played no statistically significant role in HC use nor WHO score. CONCLUSIONS: Scalp cooling is effective for the majority of patients. The robust model for evaluating the drug and dose-specific determinants of SC efficacy revealed no indications for changes in daily practice, suggesting factors currently being overlooked. As no correlation was identified between the determinants explaining HC use and WHO score outcomes, new methods for evaluation are warranted.

7.
Sci Total Environ ; 945: 174065, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38897470

RESUMO

Kelps are recognized for providing many ecosystem services in coastal areas and considered in ocean acidification (OA) mitigation. However, assessing OA modification requires an understanding of the multiple parameters involved in carbonate chemistry, especially in highly dynamic systems. We studied the effects of sugar kelp (Saccharina latissima) on an experimental farm at the north end of Hood Canal, Washington-a low retentive coastal system. In this field mesocosm study, two oyster species (Magallana gigas, Ostrea lurida) were exposed at locations in the mid, edge, and outside the kelp array. The Hood Head Sugar Kelp Farm Model outputs were used to identify dominating factors in spatial and temporal kelp dynamics, while wavelet spectrum analyses helped in understanding predictability patterns. This was linked to the measured biological responses (dissolution, growth, isotopes) of the exposed organisms. Positioned in an area of high (sub)-diel tidal fluxes with low retention potential, there were no measurable alterations of the seawater pH at the study site, demonstrating that the kelp array could not induce a direct mitigating effect against OA. However, beneficial responses in calcifiers were still observed, which are linked to two causes: increased pH predictability and improved provisioning through kelp-derived particulate organic resource utilization and as such, kelp improved habitat suitability and indirectly created refugia against OA. This study can serve as an analogue for many coastal bay habitats where prevailing physical forcing drives chemical changes. Future macrophyte studies that investigate OA mitigating effects should focus also on the importance of predictability patterns, which can additionally improve the conditions for marine calcifiers and ecosystem services vulnerable to or compromised by OA, including aquaculture sustainability.


Assuntos
Kelp , Água do Mar , Água do Mar/química , Concentração de Íons de Hidrogênio , Animais , Refúgio de Vida Selvagem , Washington , Ecossistema , Monitoramento Ambiental , Ostreidae , Acidificação dos Oceanos
8.
J Sch Health ; 94(8): 768-776, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38637288

RESUMO

BACKGROUND: School Resource Officer (SRO) programs do not reduce school violence and increase school discipline. We describe the use of a culturally responsive framework to form a school community collaborative among students, parents, staff, administrators, and law enforcement to reform an SRO program, promote school safety, and reduce punitive measures. METHODS: Members of a participating school district, a local county, and a university collaborated. Adapting an identified culturally responsive model, a racially/ethnically diverse school community co-developed and implemented a School Community Collaborative (SCC) to address a school safety priority (SRO program reform). The main outcomes were SCC model development and implementation, policy change, and school community feedback. RESULTS: Sixteen community members participated in the 5-week SCC with students, staff, law enforcement, and parents. The SCC revised the district's SRO memorandum of understanding (MOU) with law enforcement. Participants reported favorable feedback, and 89% reported the inclusion of diverse voices. CONCLUSIONS: Co-development and implementation of an SCC process with schools were feasible. School SCC participated in a community-engaged evaluation and revision of an MOU.


Assuntos
Instituições Acadêmicas , Humanos , Instituições Acadêmicas/organização & administração , Segurança , Aplicação da Lei , Comportamento Cooperativo , Estudantes , Relações Comunidade-Instituição , Violência/prevenção & controle , Desenvolvimento de Programas , Criança , Masculino , Feminino , Participação da Comunidade/métodos
9.
Chaos ; 34(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38579146

RESUMO

In this paper, we analyze the dynamic effect of a reservoir computer (RC) on its performance. Modified Kuramoto's coupled oscillators are used to model the RC, and synchronization, Lyapunov spectrum (and dimension), Shannon entropy, and the upper bound of the Kolmogorov-Sinai entropy are employed to characterize the dynamics of the RC. The performance of the RC is analyzed by reproducing the distribution of random, Gaussian, and quantum jumps series (shelved states) since a replica of the time evolution of a completely random series is not possible to generate. We demonstrate that hyperchaotic motion, moderate Shannon entropy, and a higher degree of synchronization of Kuramoto's oscillators lead to the best performance of the RC. Therefore, an appropriate balance of irregularity and order in the oscillator's dynamics leads to better performances.

10.
J Womens Pelvic Health Phys Ther ; 48(2): 91-102, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38659609

RESUMO

Background: The rating of perceived exertion (RPE) is a readily available and practical tool widely used in exercise science to monitor exercise load, but a rigorous review of the effect of menstrual cycle (MC) phases on RPE within continuous aerobic exercise has not yet been completed. Objective: This study investigated the effects of the MC phase on RPE during aerobic exercise. Study Design: This was a systematic review and meta-analysis. Methods: The search strategy was carried out using the 5 most common scientific databases. While qualitative analyses were performed in all included studies, random effects to standard mean difference were calculated and meta-analysis was performed where possible. This study addresses comparison for RPE at the beginning, middle, and end of the exercise adopting 2 mains analysis. The first adopted early cycle (first session of the cycle) as control compared with the subsequent phases, and the second adopted days 1 to 5 (early follicular) as control compared with the subsequent phases. Results: A total of 17 studies (n = 160) were included in the qualitative synthesis. The meta-analysis showed that MC phases did not impact RPE (P > .05). Conclusions: The current meta-analysis showed that MC does not impact RPE. Although acute RPE is not impacted by MC phases, future studies and practitioners should pay attention to the impact of RPE session by session throughout the MC.

11.
Cureus ; 16(3): e57075, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38681475

RESUMO

OBJECTIVE: This study aims to investigate if there is an increased risk of developing tracheal stenosis after tracheostomy with an open versus percutaneous tracheostomy. METHODS: The patient cohort included patients receiving open or percutaneous tracheostomies at Catholic Health Initiatives Midwest facilities from January 2017 to June 2023. The primary aim was to compare the differences in the risk of developing tracheal stenosis between open and percutaneous tracheostomy techniques. Between-technique differences in the risk of developing tracheal stenosis were assessed via a Cox proportional hazard model. To account for death precluding patients from developing tracheal stenosis, death was considered a competing risk. RESULTS: A total of 828 patients met inclusion criteria (61.7% open, 38.3% percutaneous); 2.5% (N = 21) developed tracheal stenosis. The median number of days to develop tracheal stenosis was 84 (interquartile range: 60 to 243, range: 6 to 739). Tracheal stenosis was more frequent in patients who received a percutaneous tracheostomy (percutaneous: 3.5% vs. open: 2.0%); however, the risk of developing tracheal stenosis was statistically similar between open and percutaneous techniques (HR: 2.05, 95% CI: 0.86-4.94, p = 0.108). CONCLUSIONS: This study demonstrates no significant difference in the development of tracheal stenosis when performing an open versus a percutaneous tracheostomy. Tracheal stenosis is a long-term complication of tracheostomy and should not influence the decision about the surgical technique used.

12.
Psychol Sport Exerc ; 73: 102637, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38615898

RESUMO

Recent studies have examined the relations between the slope of pleasure experienced during exercise and remembered pleasure, forecasted pleasure, and enjoyment. OBJECTIVES: This study advances this line of research by examining the effects of exposing participants to exercise that increases in intensity and then decreases in intensity. METHODS: In a within-subjects design, participants completed three exercise sessions matched for total and average work. One session steadily increased in intensity, another steadily decreased in intensity, and a third increased-then-decreased in intensity. Remembered pleasure, forecasted pleasure, and exercise enjoyment served as primary outcome variables. RESULTS: Remembered pleasure, forecasted pleasure, and enjoyment did not differ between conditions. Remembered pleasure was positively associated with mean experienced pleasure, the overall slope of pleasure during the exercise session, affect experienced at the end of exercise, forecasted pleasure, accomplishment, and enjoyment. CONCLUSIONS: These data add to a growing literature on the effects of patterns of exercise intensity on affective responses to exercise. The results are discussed in context of previous and more recent research.


Assuntos
Exercício Físico , Prazer , Humanos , Exercício Físico/psicologia , Exercício Físico/fisiologia , Masculino , Feminino , Adulto Jovem , Adulto , Afeto/fisiologia
13.
Inorg Chem ; 63(14): 6184-6191, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38546051

RESUMO

Secondary coordination sphere ligand effects can be used to direct or organize small molecule substrates at a metal center. Herein, we assess the bifunctional ambiphilic diphosphine, tri-tert-butylboranyldiphosphinoethane (ttbbpe) and its ability to influence stereoselective substrate coordination, while appended to nickel. This report takes a synthetic/computational approach to test the impacts and limitations associated with ligand-directed substrate coordination using [Ni(ttbbpe)(η2:η2-COD)] (COD = 1,5-cyclooctadiene) and ynones (alkynes having an α-carbonyl group at the propargylic position) as model substrates.

14.
Med Sci Sports Exerc ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38555489

RESUMO

INTRODUCTION: Although there is potential for the menstrual cycle to impact psychophysiological responses to exercise, there has been a paucity of studies investigating this aspect, specifically in the context of high-intensity interval training (HIIT). PURPOSE: This exploratory study aimed to examine the psychophysiological responses to HIIT over the menstrual cycle. METHODS: Twenty-three healthy and physically active young women were recruited. Each woman completed a cycle ergometer HIIT session in the menstrual, follicular, and luteal phases of the menstrual cycle in a random order. Psychophysiological variables of interest were collected at baseline, and during and after exercise. Primary variables of interest were anxiety, mood, motivation, enjoyment, arousal, affect, and menstrual distress. RESULTS: Higher pain, water retention, behavior change (related to social interactions, eating habits, and self-performance), and autonomic reactions (consisting of nausea, dizziness, hot flashes, and cold sweats) were observed before HIIT during the menstrual phase compared to the follicular phase (p < 0.05). Participants exhibited worse psychological responses to HIIT sessions during the menstrual phase, followed by the luteal phase. Findings also noted participants arrived to the laboratory with lower motivation to initiate HIIT sessions during the luteal and menstrual phases compared to the follicular phase. This difference was observed before and during HIIT. Motivation and depressive symptoms showed a significant reduction from pre-HIIT to post-HIIT (p < 0.05), regardless of menstrual phase. CONCLUSIONS: The findings revealed that the menstrual cycle had a significant impact on psychophysiological responses. Moreover, HIIT could be adopted to improve motivation and depressive symptoms, however, further research is needed to explore the effects of HIIT across the menstrual cycle in women with clinical depression.

15.
ChemSusChem ; 17(13): e202400039, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38358843

RESUMO

Carbon dioxide (CO2) is a potent greenhouse gas of environmental concern. Seeking to offer a solution to the "CO2-problem", the chemistry community has turned a focus toward transition metal complexes which can activate, reduce, and convert CO2 into carbon-based products. The design of such systems involves judicious selection of both metal and accompanying donor ligand; in part, these efforts are motivated by biological metalloenzymes that undertake similar transformations. As a design element, metal-ligand cooperativity, which leverages intramolecular interactions between a transition metal and an adjacent secondary ligand site, has been acknowledged as a vitally important component by the CO2 activation community. These systems offer a "push-pull" style of activation where electron density is chaperoned onto CO2 with an accompanying electrophile, such as a Lewis-acid, playing the role of acceptor. This pairing allows for the stabilization of reactive CxHyOz-containing intermediates and can bias CO2 product selectivity. In the laboratory, chemists can test hypotheses and ideas, enabling rationalization of why a given pairing of transition metal/Lewis-acid leads to selective CO2 reduction outcomes. This Concept identifies literature examples and highlights key design properties, allowing interested contributors to design, create, and implement novel systems for productive transformations of a small molecule (CO2) with huge potential impact.

16.
J Neurosci Methods ; 405: 110084, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38401804

RESUMO

The EQIPD Quality System (QS) was conceptualized and established by an international consortium consisting of academic and industrial partners to ensure that non-regulated biomedical research will be conducted according to Good Research Practice expectations. The QS supports researchers to reflect on and improve internal practices by providing a systematic framework and guidance for implementing the EQIPD QS in a time and cost effective manner. This report describes the content of the EQIPD QS with its key features and 18 Core Requirements (CR) in more detail. It gives a short background on each CR and hands on examples on how they were addressed by two different research labs in their respective laboratory environments. Thereby, this article provides examples and direction for other research labs who aim to implement the QS as well. The final paragraphs discuss the potential benefits of the QS in respect to different user groups and stakeholders within the scientific community and summarize the overall governance structure of the EQIPD framework.


Assuntos
Pesquisa Biomédica , Pesquisa Biomédica/normas
17.
Breast Cancer Res Treat ; 205(2): 287-302, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38381274

RESUMO

PURPOSE: The aim was to determine whether the real-world first-line progression-free survival (PFS) of patients diagnosed with de novo human epidermal growth factor receptor 2 positive (HER2+) advanced breast cancer (ABC) has improved since the introduction of pertuzumab in 2013. In addition to PFS, we aimed to determine differences in overall survival (OS) and the use of systemic and locoregional therapies. METHODS: Included were patients systemically treated for de novo HER2+ ABC in ten hospitals in 2008-2017 from the SONABRE Registry (NCT-03577197). First-line PFS and OS in 2013-2017 versus 2008-2012 was determined using Kaplan-Meier analyses and multivariable Cox proportional hazards modelling. First-given systemic therapy and the use of locoregional therapy within the first year following diagnosis were determined per period of diagnosis. RESULTS: Median and five-year PFS were 26.6 months and 24% in 2013-2017 (n = 85) versus 14.5 months and 10% in 2008-2012 (n = 81) (adjusted HR = 0.65, 95%CI:0.45-0.94). Median and five-year OS were 61.2 months and 51% in 2013-2017 versus 26.1 months and 28% in 2008-2012 (adjusted HR = 0.55, 95%CI:0.37-0.81). Of patients diagnosed in 2013-2017 versus 2008-2012, 84% versus 60% received HER2-targeted therapy and 59% versus 0% pertuzumab-based therapy as first-given therapy. Respectively, 27% and 23% of patients underwent locoregional breast surgery, and 6% and 7% surgery of a metastatic site during the first year following diagnosis. CONCLUSION: The prognosis of patients with de novo HER2 + ABC has improved considerably. Since 2013 one in four patients were alive and free from progression on first-given therapy for at least five years.


Assuntos
Neoplasias da Mama , Receptor ErbB-2 , Sistema de Registros , Humanos , Feminino , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Receptor ErbB-2/metabolismo , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Metástase Neoplásica , Estimativa de Kaplan-Meier , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico
18.
Nat Commun ; 15(1): 1763, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409214

RESUMO

The morphology of protein assemblies impacts their behaviour and contributes to beneficial and aberrant cellular responses. While single-molecule localization microscopy provides the required spatial resolution to investigate these assemblies, the lack of universal robust analytical tools to extract and quantify underlying structures limits this powerful technique. Here we present SEMORE, a semi-automatic machine learning framework for universal, system- and input-dependent, analysis of super-resolution data. SEMORE implements a multi-layered density-based clustering module to dissect biological assemblies and a morphology fingerprinting module for quantification by multiple geometric and kinetics-based descriptors. We demonstrate SEMORE on simulations and diverse raw super-resolution data: time-resolved insulin aggregates, and published data of dSTORM imaging of nuclear pore complexes, fibroblast growth receptor 1, sptPALM of Syntaxin 1a and dynamic live-cell PALM of ryanodine receptors. SEMORE extracts and quantifies all protein assemblies, their temporal morphology evolution and provides quantitative insights, e.g. classification of heterogeneous insulin aggregation pathways and NPC geometry in minutes. SEMORE is a general analysis platform for super-resolution data, and being a time-aware framework can also support the rise of 4D super-resolution data.


Assuntos
Insulinas , Imagem Individual de Molécula , Imagem Individual de Molécula/métodos , Fibroblastos , Aprendizado de Máquina , Análise de Dados
19.
Ecol Evol ; 14(1): e10842, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38235407

RESUMO

Since the classic work of E.B. Ford, explanations for eyespot variation in the Meadow Brown butterfly have focused on the role of genetic polymorphism. The potential role of thermal plasticity in this classic example of natural selection has therefore been overlooked. Here, we use large daily field collections of butterflies from three sites, over multiple years, to examine whether field temperature is correlated with eyespot variation, using the same presence/absence scoring as Ford. We show that higher developmental temperature in the field leads to the disappearance of the spots visible while the butterfly is at rest, explaining the historical observation that hindwing spotting declines across the season. Strikingly, females developing at 11°C have a median of six spots and those developing at 15°C only have three. In contrast, the large forewing eyespot is always present and scales with forewing length. Furthermore, in contrast to the smaller spots, the size of the large forewing spot is best explained by calendar date (days since 1st March) rather than the temperature at pupation. As this large forewing spot is involved in startling predators and/or sexual selection, its constant presence is therefore likely required for defence, whereas the disappearance of the smaller spots over the season may help with female crypsis. We model annual total spot variation with phenological data from the UK and derive predictions as to how spot patterns will continue to change, predicting that female spotting will decrease year on year as our climate warms.

20.
medRxiv ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38260271

RESUMO

While whole genome sequencing (WGS) of cell-free DNA (cfDNA) holds enormous promise for molecular residual disease (MRD) detection, its performance is limited by WGS error rate. Here we introduce AccuScan, an efficient cfDNA WGS technology that enables genome-wide error correction at single read level, achieving an error rate of 4.2×10 -7 , which is about two orders of magnitude lower than a read-centric de-noising method. When applied to MRD detection, AccuScan demonstrated analytical sensitivity down to 10 -6 circulating tumor allele fraction at 99% sample level specificity. In colorectal cancer, AccuScan showed 90% landmark sensitivity for predicting relapse. It also showed robust MRD performance with esophageal cancer using samples collected as early as 1 week after surgery, and predictive value for immunotherapy monitoring with melanoma patients. Overall, AccuScan provides a highly accurate WGS solution for MRD, empowering circulating tumor DNA detection at parts per million range without high sample input nor personalized reagents. One Sentence Summary: AccuScan showed remarkable ultra-low limit of detection with a short turnaround time, low sample requirement and a simple workflow for MRD detection.

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