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We have structurally characterized the liquid crystal (LC) phase that can appear as an intermediate state when a dielectric nematic, having polar disorder of its molecular dipoles, transitions to the almost perfectly polar-ordered ferroelectric nematic. This intermediate phase, which fills a 100-y-old void in the taxonomy of smectic LCs and which we term the "smectic ZA," is antiferroelectric, with the nematic director and polarization oriented parallel to smectic layer planes, and the polarization alternating in sign from layer to layer with a 180 Å period. A Landau free energy, originally derived from the Ising model of ferromagnetic ordering of spins in the presence of dipole-dipole interactions, and applied to model incommensurate antiferroelectricity in crystals, describes the key features of the nematic-SmZA-ferroelectric nematic phase sequence.
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BACKGROUND: The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1. METHODS: Tissues from animal pulmonary hypertension models as well as human pulmonary artery endothelial cells from patients with PAH exhibited increased vascular UCHL1 staining and protein expression. Exposure to LDN57444, a UCHL1-specific inhibitor, reduced human pulmonary artery endothelial cell and smooth muscle cell proliferation. Across 3 preclinical PAH models, LDN57444-exposed animals, Uchl1 knockout rats (Uchl1-/-), and conditional Uchl1 knockout mice (Tie2Cre-Uchl1fl/fl) demonstrated reduced right ventricular hypertrophy, right ventricular systolic pressures, and obliterative vascular remodeling. Lungs and pulmonary artery endothelial cells isolated from Uchl1-/- animals exhibited reduced total and activated Akt with increased ubiquitinated Akt levels. UCHL1-silenced human pulmonary artery endothelial cells displayed reduced lysine(K)63-linked and increased K48-linked AKT1 levels. RESULTS: Supporting experimental data, we found that rs9321, a variant in a GC-enriched region of the UCHL1 gene, is associated with reduced methylation (n=5133), increased UCHL1 gene expression in lungs (n=815), and reduced cardiac index in patients (n=796). In addition, Gadd45α (an established demethylating gene) knockout mice (Gadd45α-/-) exhibited reduced lung vascular UCHL1 and AKT1 expression along with attenuated hypoxic pulmonary hypertension. CONCLUSIONS: Our findings suggest that UCHL1 deficiency results in PAH attenuation by means of reduced AKT1, highlighting a novel therapeutic pathway in PAH.
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Camundongos Knockout , Proteínas Proto-Oncogênicas c-akt , Ubiquitina Tiolesterase , Animais , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/deficiência , Ubiquitina Tiolesterase/metabolismo , Humanos , Camundongos , Ratos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Masculino , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/genética , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Células Endoteliais/enzimologia , Ratos Sprague-Dawley , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/etiologia , Remodelação Vascular , Células Cultivadas , Proliferação de Células , Camundongos Endogâmicos C57BL , Indóis , OximasRESUMO
We investigated the electrostatic behavior of ferroelectric liquid droplets exposed to the pyroelectric field of a lithium niobate ferroelectric crystal substrate. The ferroelectric liquid is a nematic liquid crystal, in which almost complete polar ordering of the molecular dipoles generates an internal macroscopic polarization locally collinear to the mean molecular long axis. Upon entering the ferroelectric phase by reducing the temperature from the nematic phase, the liquid crystal droplets become electromechanically unstable and disintegrate by the explosive emission of fluid jets. These jets are mostly interfacial, spreading out on the substrate surface, and exhibit fractal branching out into smaller streams to eventually disrupt, forming secondary droplets. We understand this behavior as a manifestation of the Rayleigh instability of electrically charged fluid droplets, expected when the electrostatic repulsion exceeds the surface tension of the fluid. In this case, the charges are due to the bulk polarization of the ferroelectric fluid, which couples to the pyroelectric polarization of the underlying lithium niobate substrate through its fringing field and solid-fluid interface coupling. Since the ejection of fluid does not neutralize the droplet surfaces, they can undergo multiple explosive events as the temperature decreases.
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We report the observation of the smectic AF, a liquid crystal phase of the ferroelectric nematic realm. The smectic AF is a phase of small polar, rod-shaped molecules that form two-dimensional fluid layers spaced by approximately the mean molecular length. The phase is uniaxial, with the molecular director, the local average long-axis orientation, normal to the layer planes, and ferroelectric, with a spontaneous electric polarization parallel to the director. Polarization measurements indicate almost complete polar ordering of the â¼10 Debye longitudinal molecular dipoles, and hysteretic polarization reversal with a coercive field â¼2 × 105 V/m is observed. The SmAF phase appears upon cooling in two binary mixtures of partially fluorinated mesogens: 2N/DIO, exhibiting a nematic (N)-smectic ZA (SmZA)-ferroelectric nematic (NF)-SmAF phase sequence, and 7N/DIO, exhibiting an N-SmZA-SmAF phase sequence. The latter presents an opportunity to study a transition between two smectic phases having orthogonal systems of layers.
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SIGNIFICANCE: The availability of a range of effective myopia control modalities enables the clinician to exercise judgment when discussing the treatment plan with the patient and their parents. This article outlines important considerations beyond efficacy.Clinically meaningful myopia control may be attained with some spectacle lenses, select soft contact lenses, some concentrations of atropine, and overnight orthokeratology. Given that satisfactory efficacy can be achieved with a range of modalities, other factors should be considered when deciding upon the best intervention for a given child. Four key factors-compliance, quality of vision, quality of life, and safety-are discussed in this review. Compliance directly impacts efficacy regardless of the modality and is the most important consideration, as it is influenced by quality of vision and comfort. Daily disposal myopia control contact lenses and overnight orthokeratology are generally associated with high compliance, provide better vision-related quality of life than spectacles, and carry a very low risk when used appropriately. A further benefit of overnight orthokeratology is the elimination of a need for optical correction during the day.
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Lentes de Contato Hidrofílicas , Miopia , Criança , Humanos , Qualidade de Vida , Miopia/terapia , Atropina , Exercício FísicoRESUMO
We show that surface interactions can vectorially structure the three-dimensional polarization field of a ferroelectric fluid. The contact between a ferroelectric nematic liquid crystal and a surface with in-plane polarity generates a preferred in-plane orientation of the polarization field at that interface. This is a route to the formation of fluid or glassy monodomains of high polarization without the need for electric field poling. For example, unidirectional buffing of polyimide films on planar surfaces to give quadrupolar in-plane anisotropy also induces macroscopic in-plane polar order at the surfaces, enabling the formation of a variety of azimuthal polar director structures in the cell interior, including uniform and twisted states. In a π-twist cell, obtained with antiparallel, unidirectional buffing on opposing surfaces, we demonstrate three distinct modes of ferroelectric nematic electro-optic response: intrinsic, viscosity-limited, field-induced molecular reorientation; field-induced motion of domain walls separating twisted states of opposite chirality; and propagation of polarization reorientation solitons from the cell plates to the cell center upon field reversal. Chirally doped ferroelectric nematics in antiparallel-rubbed cells produce Grandjean textures of helical twist that can be unwound via field-induced polar surface reorientation transitions. Fields required are in the 3-V/mm range, indicating an in-plane polar anchoring energy of w P â¼3 × 10-3 J/m2.
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Although its mesomorphic properties have been studied for many years, only recently has the molecule of life begun to reveal the true range of its rich liquid crystalline behavior. End-to-end interactions between concentrated, ultrashort DNA duplexes-driving the self-assembly of aggregates that organize into liquid crystal phases-and the incorporation of flexible single-stranded "gaps" in otherwise fully paired duplexes-producing clear evidence of an elementary lamellar (smectic-A) phase in DNA solutions-are two exciting developments that have opened avenues for discovery. Here, we report on a wider investigation of the nature and temperature dependence of smectic ordering in concentrated solutions of various "gapped" DNA (GDNA) constructs. We examine symmetric GDNA constructs consisting of two 48-base pair duplex segments bridged by a single-stranded sequence of 2 to 20 thymine bases. Two distinct smectic layer structures are observed for DNA concentration in the range [Formula: see text] mg/mL. One exhibits an interlayer periodicity comparable with two-duplex lengths ("bilayer" structure), and the other has a period similar to a single-duplex length ("monolayer" structure). The bilayer structure is observed for gap length â³10 bases and melts into the cholesteric phase at a temperature between 30 °C and 35 °C. The monolayer structure predominates for gap length â²10 bases and persists to [Formula: see text]C. We discuss models for the two layer structures and mechanisms for their stability. We also report results for asymmetric gapped constructs and for constructs with terminal overhangs, which further support the model layer structures.
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DNA/química , Cristais Líquidos/química , Estrutura Molecular , SoluçõesRESUMO
BACKGROUND: Obesity can be a source of higher failure rates and inferior clinical outcomes after total knee arthroplasty (TKA). The aim of this study was to compare outcomes, failure rates, and stress distributions of TKA in obese patients using a short, long, or no tibial stem. METHODS: A matching process based on the type of stem used and the age allowed included 180 patients who had a body mass index (BMI) > 30 and underwent a TKA between January 2010 and December 2019, with a minimum follow-up of 2 years. They were classified as moderately obese (MO: 30 < BMI < 35, N = 90) and severely obese (SO: BMI > 35, N = 90). For each, 3 subgroups were defined: thirty patients received a 30 mm short stem (SS), thirty received a 100 mm long stem (LS), and thirty received no stem (NS). Patients were assessed preoperatively and postoperatively using the Knee Society Score (KSS). A finite element model was developed to evaluate the biomechanical effects of the tibial stem on stress distribution in the subchondral bone based on BMI. RESULTS: The SS patients had significantly higher postoperative KSS knee score [MO: 88.9 (SS) versus 79 (LS) versus 80.6 (NS); SO: 84.5 versus 72.4 versus 78.2] (P < .0001) and function score [MO: 90.4 (SS) versus 78.4 (LS) versus 68.5 (NS); SO: 85.5 versus 73 versus 61.8] (P < .0001) compared to LS and NS patients. The biomechanical study demonstrated a BMI-dependent increase in stress in the subchondral bone in contact with the tibial components. These stresses were mainly distributed at the tibial cut for NS and along the stem for SS and LS. CONCLUSIONS: A short, cemented tibial stem offers better functional outcomes without increasing failure rates compared to a longer stem during primary TKA in a population of obese patients at two-year follow-up. A short tibial stem does not lead to increased stress compared to an LS, at least for certain BMI categories.
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Artroplastia do Joelho , Prótese do Joelho , Obesidade , Tíbia , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Obesidade/complicações , Seguimentos , Fenômenos Biomecânicos , Tíbia/cirurgia , Resultado do Tratamento , Índice de Massa Corporal , Desenho de Prótese , Articulação do Joelho/cirurgia , Articulação do Joelho/fisiopatologia , Falha de Prótese , Osteoartrite do Joelho/cirurgia , Análise de Elementos Finitos , Estudos RetrospectivosRESUMO
PURPOSE: Myopia severity has a profound impact on visual impairment in later life. A patient's final level of myopia may be lowered by myopia control, but also by delaying onset. Here, we evaluate the influence of the age of onset on the final recorded level of myopia. METHODS: Data were extracted from: (1) Three prospective cohort studies of myopia progression in East Asia and the United States where the final recorded level of myopia is presented as a function of the established age of onset. (2) Four retrospective studies of myopia progression in Finland, India, the Netherlands and China and two cross-sectional studies in Argentina and the UK where the age of onset was based on self-report of age at first spectacle prescription. (3) A cohort study of Finnish subjects originally recruited for a clinical trial and followed into adulthood. Subjects were divided into five groups according to age at recruitment that was used as a surrogate for the age of onset. RESULTS: Final recorded level of myopia was plotted as a function of age of onset for all studies. Among the three East Asian studies, the slopes are between 0.68 and 0.97 D/year, meaning that each later year of onset is associated with between 0.68 and 0.97 less myopia at the final recorded refraction. For six of the seven non-East Asian studies, the slopes are substantially flatter, with slopes between 0.23 and 0.50 D/year. By contrast, the slope for the Finnish study was 0.87 D/year. Increasing age of final recorded refraction tended to be associated with higher levels of myopia. CONCLUSION: Among East Asians, delaying the onset of myopia by 1 year has the potential to lower the final myopia level by 0.75 D or more-equivalent to 2-3 years of myopia control with existing modalities. The benefit is lower, but meaningful, among non-East Asians.
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Estudos de Coortes , Humanos , Adulto , Estudos Transversais , Estudos Prospectivos , Estudos Retrospectivos , ChinaRESUMO
In the field of myopia control, effective optical or pharmaceutical therapies are now available to patients in many markets. This creates challenges for the conduct of placebo-controlled, randomised clinical trials, including ethics, recruitment, retention, selective loss of faster progressors and non-protocol treatments: Ethics: It is valid to question whether withholding treatment in control subjects is ethical. Recruitment: Availability of treatments is making recruitment into clinical trials more difficult. Retention: If masking is not possible, parents may immediately withdraw their child if randomised to no treatment. Selective loss: Withdrawal of fast progressors in the control group leading to a control group biased towards low progression. Non-protocol treatment: Parents may access other myopia treatments in addition to those within the trial. We propose that future trials may adopt one of the following designs: Non-inferiority trials using an approved drug or device as the control. The choice will depend on whether a regulatory agency has approved the drug or device. Short conventional efficacy trials where data are subsequently entered into a model created from previous clinical trials, which allows robust prediction of long-term treatment efficacy from the initial efficacy. Virtual control group trials based on data relating to axial elongation, myopia progression or both, accounting for subject's age and race. Short-term control data from a cohort, for example, 1 year or less, and applying an appropriate, proportional annual reduction in axial elongation to that population and extrapolating to subsequent years. Time-to-treatment-failure trials using survival analysis; once a treated or control subject progresses or elongates by a given amount, they exit the study and can be offered treatment. In summary, the future development of new treatments in myopia control will be hampered if significant changes are not made to the design of clinical trials in this area.
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Miopia , Criança , Humanos , Resultado do Tratamento , Miopia/prevenção & controleRESUMO
We report the experimental determination of the structure and response to applied electric field of the lower-temperature nematic phase of the previously reported calamitic compound 4-[(4-nitrophenoxy)carbonyl]phenyl2,4-dimethoxybenzoate (RM734). We exploit its electro-optics to visualize the appearance, in the absence of applied field, of a permanent electric polarization density, manifested as a spontaneously broken symmetry in distinct domains of opposite polar orientation. Polarization reversal is mediated by field-induced domain wall movement, making this phase ferroelectric, a 3D uniaxial nematic having a spontaneous, reorientable polarization locally parallel to the director. This polarization density saturates at a low temperature value of â¼6 µC/cm2, the largest ever measured for a fluid or glassy material. This polarization is comparable to that of solid state ferroelectrics and is close to the average value obtained by assuming perfect, polar alignment of molecular dipoles in the nematic. We find a host of spectacular optical and hydrodynamic effects driven by ultralow applied field (E â¼ 1 V/cm), produced by the coupling of the large polarization to nematic birefringence and flow. Electrostatic self-interaction of the polarization charge renders the transition from the nematic phase mean field-like and weakly first order and controls the director field structure of the ferroelectric phase. Atomistic molecular dynamics simulation reveals short-range polar molecular interactions that favor ferroelectric ordering, including a tendency for head-to-tail association into polar, chain-like assemblies having polar lateral correlations. These results indicate a significant potential for transformative, new nematic physics, chemistry, and applications based on the enhanced understanding, development, and exploitation of molecular electrostatic interaction.
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Here, we report the relationship between helical pitch of the helical nanofilament (HNF) phase formed by bent-core molecule NOBOW and the concentration of achiral dopants 5CB and octane, using linearly polarized resonant soft X-ray scattering (RSoXS). Utilizing theory-based simulation, which fits well with the experiments, the molecular helices in the filament were probed and the superstructure of helical 5CB directed by groove of HNFs was observed. Quantitative pitch determination with RSoXS reveals that helical pitch variation is related to 5CB concentration with no temperature dependence. Doping rodlike immiscible 5CB led to a pitch shortening of up to 30%, which was attributed to a change in interfacial tension. By shedding light not only on phase behavior of binary systems but also enabling control over pitch length, our work may benefit various applications of HNF-containing binary systems, including optical rotation devices, circularly polarized light emitters, and chirality transfer agents.
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Cristais Líquidos , Simulação por Computador , Cristais Líquidos/química , TemperaturaRESUMO
PROTACs have emerged as a new class of drugs that can target the "undruggable" proteome by hijacking the ubiquitin proteasome system. Despite PROTACs' success, most current PROTACs interface with a limited number of E3 ligases, hindering their expansion to many challenging therapeutic uses. Currently, PROTAC drug discovery relies heavily on traditional Western blotting and reporter gene assays which are insensitive and prone to artifacts, respectively. New reliable methods to monitor true PROTAC function (i.e., ubiquitination and subsequent degradation of targets at physiological expression levels) without external tags are essential to accelerate the PROTAC discovery process and to address many unmet therapeutic areas. In this study, we developed a new high-throughput screening technology using "TUBEs" as ubiquitin-binding entities to monitor PROTAC-mediated poly-ubiquitination of native target proteins with exceptional sensitivity. As a proof of concept, targets including BRD3, Aurora A Kinase, and KRAS were used to demonstrate that ubiquitination kinetics can reliably establish the rank order potencies of PROTAC with variable ligands and linkers. PROTAC-treated cell lysates with the highest levels of endogenous target protein ubiquitination - termed "UbMax" - display excellent correlations with DC50 values obtained from traditional Western blots with the added benefits of being high throughput, providing improved sensitivity, and reducing technical errors.
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Aurora Quinase A , Complexo de Endopeptidases do Proteassoma , Aurora Quinase A/metabolismo , Descoberta de Drogas/métodos , Ligantes , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Proteoma/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Ubiquitinas/metabolismoRESUMO
A few members of the bacterial genus Thermus have been shown to be incomplete denitrifiers, terminating with nitrite (NO2-) or nitrous oxide (N2O). However, the denitrification abilities of the genus as a whole remain poorly characterized. Here, we describe diverse denitrification phenotypes and genotypes of a collection of 24 strains representing ten species, all isolated from a variety of geothermal systems in China. Confirmed terminal products of nitrate reduction were nitrite or N2O, while nitric oxide (NO) was inferred as the terminal product in some strains. Most strains produced N2O; complete denitrification was not observed. Denitrification phenotypes were largely consistent with the presence of denitrification genes, and strains of the same species often had the same denitrification phenotypes and largely syntenous denitrification gene clusters. Genes for nirS and nirK coexisted in three Thermus brockianus and three Thermus oshimai genomes, which is a unique hallmark of some denitrifying Thermus strains and may be ecologically important. These results show that incomplete denitrification phenotypes are prominent, but variable, within and between Thermus species. The incomplete denitrification phenotypes described here suggest Thermus species may play important roles in consortial denitrification in high-temperature terrestrial biotopes where sufficient supply of oxidized inorganic nitrogen exists.
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Fontes Termais , Solo , Nitritos , Fenótipo , Thermus/genéticaRESUMO
Correction for 'Surface alignment of ferroelectric nematic liquid crystals' by Federico Caimi et al., Soft Matter, 2021, 17, 8130-8139, https://doi.org/10.1039/D1SM00734C.
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To determine the distribution and causes of extinction threat across functional groups of terrestrial vertebrates, we assembled an ecological trait data set for 18,016 species of terrestrial vertebrates and utilized phylogenetic comparative methods to test which categories of habitat association, mode of locomotion, and feeding mode best predicted extinction risk. We also examined the individual categories of the International Union for Conservation of Nature Red List extinction drivers (e.g., agriculture and logging) threatening each species and determined the greatest threats for each of the four terrestrial vertebrate groups. We then quantified the sum of extinction drivers threatening each species to provide a multistressor perspective on threat. Cave dwelling amphibians (p < 0.01), arboreal quadrupedal mammals (all of which are primates) (p < 0.01), aerial and scavenging birds (p < 0.01), and pedal (i.e., walking) squamates (p < 0.01) were all disproportionately threatened with extinction in comparison with the other assessed ecological traits. Across all threatened vertebrate species in the study, the most common risk factors were agriculture, threatening 4491 species, followed by logging, threatening 3187 species, and then invasive species and disease, threatening 2053 species. Species at higher risk of extinction were simultaneously at risk from a greater number of threat types. If left unabated, the disproportionate loss of species with certain functional traits and increasing anthropogenic pressures are likely to disrupt ecosystem functions globally. A shift in focus from species- to trait-centric conservation practices will allow for protection of at-risk functional diversity from regional to global scales.
Una Señal Ecológica Mundial del Riesgo de Extinción de los Vertebrados Terrestres Resumen Construimos un conjunto de datos de atributos ecológicos de 18,016 especies de vertebrados terrestres y utilizamos métodos de comparación filogenética para analizar cuáles categorías de asociación de hábitat, modo de locomoción y modo de alimentación predicen de mejor manera el riesgo de extinción. Lo anterior lo hicimos para determinar la distribución y las causas de las amenazas de extinción a lo largo de los grupos funcionales de vertebrados terrestres. También examinamos las categorías individuales de los factores de extinción (p. ej.: agricultura, tala de árboles) de la Lista Roja de la Unión Internacional para la Conservación de la Naturaleza que amenazan a cada especie y determinamos las principales amenazas para cada uno de los cuatro grupos de vertebrados terrestres. Después cuantificamos la suma de los factores de extinción que amenazan a cada especie para proporcionar una perspectiva de estresores múltiples sobre la amenaza. Los anfibios cavernícolas (p < 0.01), mamíferos arbóreos cuadrúpedos (todos son primates) (p < 0.01), aves aéreas y carroñeras (p < 0.01) y los escamados caminantes (p < 0.01) tuvieron una amenaza de extinción desproporcionada en comparación con los otros atributos ecológicos analizados. En todas las especies de vertebrados que estudiamos, los factores de riesgo más comunes fueron la agricultura, que amenaza a 4,491 especies, y la deforestación, que amenaza a 3,187 especies; le siguen las especies invasoras y las enfermedades, que juntas amenazan a 2,053 especies. Las especies con el mayor riesgo de extinción también se encontraban simultáneamente en riesgo por un mayor número de tipos de amenazas. Si esto se mantiene constante, la pérdida desproporcionada de especies con ciertos atributos funcionales y la creciente presión antropogénica probablemente alteren las funciones ecosistémicas a nivel mundial. Un cambio en el enfoque de las prácticas de conservación, de estar centradas en la especie a estar centradas en los atributos, permitirá la protección de la diversidad funcional en riesgo desde la escala regional hasta la global.
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Ecossistema , Extinção Biológica , Animais , Biodiversidade , Conservação dos Recursos Naturais , Espécies em Perigo de Extinção , Mamíferos , Filogenia , VertebradosRESUMO
SIGNIFICANCE: Identifying children at highest risk for rapid myopia progression and/or rapid axial elongation could help prioritize who should receive clinical treatment or be enrolled in randomized clinical trials. Our models suggest that these goals are difficult to accomplish. PURPOSE: This study aimed to develop models predicting future refractive error and axial length using children's baseline data and history of myopia progression and axial elongation. METHODS: Models predicting refractive error and axial length were created using randomly assigned training and test data sets from 916 myopic participants in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study. Subjects were 7 to 14 years of age at study entry with three consecutive annual visits that included cycloplegic A-scan ultrasound and autorefraction. The effect of adding prior change in axial length and refractive error was evaluated for each model. RESULTS: Age, ethnicity, and greater myopia were significant predictors of future refractive error and axial length, whereas prior progression or elongation, near work, time outdoors, and parental myopia were not. The 95% limits for the difference between actual and predicted change were ±0.22 D and ±0.14 mm without prior change data compared with ±0.26 D and ±0.16 mm with prior change data. Sensitivity and specificity for identifying fast progressors were between 60.8 and 63.2%, respectively, when the cut points were close to the sample average. Positive predictive value and sample yield were even lower when the cut points were more extreme. CONCLUSIONS: Young, more myopic Asian American children in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study were the most likely to progress rapidly. Clinical trials should expect average progression rates that reflect sample demographics and may have difficulty recruiting generalizable samples that progress faster than that average. Knowing progression or elongation history does not seem to help the clinical decision regarding initiating myopia control.
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Miopia , Erros de Refração , Criança , Progressão da Doença , Etnicidade , Humanos , Midriáticos , Miopia/diagnóstico , Refração OcularRESUMO
We synthesized the liquid crystal dimer and trimer members of a series of flexible linear oligomers and characterized their microscopic and nanoscopic properties using resonant soft X-ray scattering and a number of other experimental techniques. On the microscopic scale, the twist-bend phases of the dimer and trimer appear essentially identical. However, while the liquid crystal dimer exhibits a temperature-dependent variation of its twist-bend helical pitch varying from 100 to 170 Å on heating, the trimer exhibits an essentially temperature-independent pitch of 66 Å, significantly shorter than those reported for other twist-bend forming materials in the literature. We attribute this to a specific combination of intrinsic conformational bend of the trimer molecules and a sterically favorable intercalation of the trimers over a commensurate fraction (two-thirds) of the molecular length. We develop a geometric model of the twist-bend phase for these materials with the molecules arranging into helical chain structures, and we fully determine their respective geometric parameters.
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The relationships between inflammation and cancer are known since the original work by Virchow in the 19th century and have been largely confirmed after-wards. An interesting question is what might be the primum movens. Numerous clinical observations have shown that a chronic inflammatory state, as that observed with some infections, toxic agents or dysimmune diseases, may be associated with the development of cancer later on. Besides, cancer is generally accompanied by an inflammatory microenvironment, with numerous cellular and humoral components, which promotes both tumorigenesis and the invasivity of the tumour. This article aims at defining the pathophysiology of this association, with a description of underlying mechanisms and mediators, and at determining possible therapeutic implications.
: Les relations entre inflammation et cancer sont connues depuis les travaux pionniers de Virchow au 19ème siècle et ont été largement confirmées depuis lors. En fait, il s'agit d'une relation à double sens et la question est de savoir quel est le primum movens. De nombreuses observations cliniques ont montré qu'un état inflammatoire chronique, tel qu'on peut l'observer avec certaines infections, certains toxiques ou encore des maladies dysimmunitaires, peut être associé, à terme, au développement d'un cancer. Par ailleurs, le cancer s'accompagne généralement d'un microenvironnement inflammatoire, avec de nombreuses composantes cellulaires et humorales, qui favorise la tumorigenèse et l'invasivité de la tumeur. Cet article a pour objectif de définir la physiopathologie de cette association, en décrivant les mécanismes et médiateurs sous-jacents, et d'en déterminer les éventuelles implications thérapeutiques.
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Inflamação , Neoplasias , Humanos , Inflamação/complicações , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Microambiente TumoralRESUMO
Assessment of the DNA photo-oxidation and synthetic photocatalytic activity of chromium polypyridyl complexes is dominated by consideration of their long-lived metal-centered excited states. Here we report the participation of the excited states of [Cr(TMP)2dppz]3+ (1) (TMP = 3,4,7,8-tetramethyl-1,10-phenanthroline; dppz = dipyrido[3,2-a:2',3'-c]phenazine) in DNA photoreactions. The interactions of enantiomers of 1 with natural DNA or with oligodeoxynucleotides with varying AT content (0-100%) have been studied by steady state UV/visible absorption and luminescence spectroscopic methods, and the emission of 1 is found to be quenched in all systems. The time-resolved infrared (TRIR) and visible absorption spectra (TA) of 1 following excitation in the region between 350 to 400 nm reveal the presence of relatively long-lived dppz-centered states which eventually yield the emissive metal-centered state. The dppz-localized states are fully quenched when bound by GC base pairs and partially so in the presence of an AT base-pair system to generate purine radical cations. The sensitized formation of the adenine radical cation species (Aâ¢+T) is identified by assigning the TRIR spectra with help of DFT calculations. In natural DNA and oligodeoxynucleotides containing a mixture of AT and GC of base pairs, the observed time-resolved spectra are consistent with eventual photo-oxidation occurring predominantly at guanine through hole migration between base pairs. The combined targeting of purines leads to enhanced photo-oxidation of guanine. These results show that DNA photo-oxidation by the intercalated 1, which locates the dppz in contact with the target purines, is dominated by the LC centered excited state. This work has implications for future phototherapeutics and photocatalysis.