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1.
Proc Natl Acad Sci U S A ; 121(6): e2312250121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38285946

RESUMO

During cell division, precise and regulated distribution of cellular material between daughter cells is a critical step and is governed by complex biochemical and biophysical mechanisms. To achieve this, membraneless organelles and condensates often require complete disassembly during mitosis. The biophysical principles governing the disassembly of condensates remain poorly understood. Here, we used a physical biology approach to study how physical and material properties of the nucleolus, a prominent nuclear membraneless organelle in eukaryotic cells, change during mitosis and across different scales. We found that nucleolus disassembly proceeds continuously through two distinct phases with a slow and reversible preparatory phase followed by a rapid irreversible phase that was concurrent with the nuclear envelope breakdown. We measured microscopic properties of nucleolar material including effective diffusion rates and binding affinities as well as key macroscopic properties of surface tension and bending rigidity. By incorporating these measurements into the framework of critical phenomena, we found evidence that near mitosis surface tension displays a power-law behavior as a function of biochemically modulated interaction strength. This two-step disassembly mechanism maintains structural and functional stability of nucleolus while enabling its rapid and efficient disassembly in response to cell cycle cues.


Assuntos
Nucléolo Celular , Mitose , Nucléolo Celular/metabolismo
2.
Proc Natl Acad Sci U S A ; 121(3): e2307996120, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38215183

RESUMO

Excitable media, ranging from bioelectric tissues and chemical oscillators to forest fires and competing populations, are nonlinear, spatially extended systems capable of spiking. Most investigations of excitable media consider situations where the amplifying and suppressing forces necessary for spiking coexist at every point in space. In this case, spikes arise due to local bistabilities, which require a fine-tuned ratio between local amplification and suppression strengths. But, in nature and engineered systems, these forces can be segregated in space, forming structures like interfaces and boundaries. Here, we show how boundaries can generate and protect spiking when the reacting components can spread out: Even arbitrarily weak diffusion can cause spiking at the edge between two non-excitable media. This edge spiking arises due to a global bistability, which can occur even if amplification and suppression strengths do not allow spiking when mixed. We analytically derive a spiking phase diagram that depends on two parameters: i) the ratio between the system size and the characteristic diffusive length-scale and ii) the ratio between the amplification and suppression strengths. Our analysis explains recent experimental observations of action potentials at the interface between two non-excitable bioelectric tissues. Beyond electrophysiology, we highlight how edge spiking emerges in predator-prey dynamics and in oscillating chemical reactions. Our findings provide a theoretical blueprint for a class of interfacial excitations in reaction-diffusion systems, with potential implications for spatially controlled chemical reactions, nonlinear waveguides and neuromorphic computation, as well as spiking instabilities, such as cardiac arrhythmias, that naturally occur in heterogeneous biological media.

3.
Proc Natl Acad Sci U S A ; 121(18): e2400313121, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38652745

RESUMO

Can liquid-like and gas-like states be distinguished beyond the critical point, where the liquid-gas phase transition no longer exists and conventionally only a single supercritical fluid phase is defined? Recent experiments and simulations report strong evidence of dynamical crossovers above the critical temperature and pressure. Despite using different criteria, many existing theoretical explanations consider a single crossover line separating liquid-like and gas-like states in the supercritical fluid phase. We argue that such a single-line scenario is inconsistent with the supercritical behavior of the Ising model, which has two crossover lines due to its symmetry, violating the universality principle of critical phenomena. To reconcile the inconsistency, we define two thermodynamic crossover lines in supercritical fluids as boundaries of liquid-like, indistinguishable, and gas-like states. Near the critical point, the two crossover lines follow critical scalings with exponents of the Ising universality class, supported by calculations of theoretical models and analyses of experimental data from the standard database. The upper line agrees with crossovers independently estimated from the inelastic X-ray scattering data of supercritical argon, and from the small-angle neutron scattering data of supercritical carbon dioxide. The lower line is verified by the equation of states for the compressibility factor. This work provides a fundamental framework for understanding supercritical physics in general phase transitions.

4.
Proc Natl Acad Sci U S A ; 121(26): e2316438121, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38900799

RESUMO

Phase transitions occurring in nonequilibrium conditions can evolve through high-energy intermediate states inaccessible via equilibrium adiabatic conditions. Because of the subtle nature of such hidden phases, their direct observation is extremely challenging and requires simultaneous visualization of matter at subpicoseconds and subpicometer scales. Here, we show that a magnetite crystal in the vicinity of its metal-to-insulator transition evolves through different hidden states when controlled via energy-tuned ultrashort laser pulses. By directly monitoring magnetite's crystal structure with ultrafast electron diffraction, we found that upon near-infrared (800 nm) excitation, the trimeron charge/orbital ordering pattern is destroyed in favor of a phase-separated state made of cubic-metallic and monoclinic-insulating regions. On the contrary, visible light (400 nm) activates a photodoping charge transfer process that further promotes the long-range order of the trimerons by stabilizing the charge density wave fluctuations, leading to the reinforcement of the monoclinic insulating phase. Our results demonstrate that magnetite's structure can evolve through completely different metastable hidden phases that can be reached long after the initial excitation has relaxed, breaking ground for a protocol to control emergent properties of matter.

5.
Proc Natl Acad Sci U S A ; 121(16): e2321665121, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38593078

RESUMO

Different mechanisms driving a linear temperature dependence of the resistivity ρ ∼ T at van Hove singularities (VHSs) or metal-insulator transitions when doping a Mott insulator are being debated intensively with competing theoretical proposals. We experimentally investigate this using the exceptional tunability of twisted bilayer (TB) WSe2 by tracking the parameter regions where linear-in-T resistivity is found in dependency of displacement fields, filling, and magnetic fields. We find that even when the VHSs are tuned rather far away from the half-filling point and the Mott insulating transition is absent, the T-linear resistivity persists at the VHSs. When doping away from the VHSs, the T-linear behavior quickly transitions into a Fermi liquid behavior with a T2 relation. No apparent dependency of the linear-in-T resistivity, besides a rather strong change of prefactor, is found when applying displacement fields as long as the filling is tuned to the VHSs, including D ∼ 0.28 V/nm where a high-order VHS is expected. Intriguingly, such non-Fermi liquid linear-in-T resistivity persists even when magnetic fields break the spin-degeneracy of the VHSs at which point two linear in T regions emerge, for each of the split VHSs separately. This points to a mechanism of enhanced scattering at generic VHSs rather than only at high-order VHSs or by a quantum critical point during a Mott transition. Our findings provide insights into the many-body consequences arising out of VHSs, especially the non-Fermi liquid behavior found in moiré materials.

6.
Annu Rev Microbiol ; 75: 515-539, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34348026

RESUMO

To reproduce, prokaryotic viruses must hijack the cellular machinery of their hosts and redirect it toward the production of viral particles. While takeover of the host replication and protein synthesis apparatus has long been considered an essential feature of infection, recent studies indicate that extensive reprogramming of host primary metabolism is a widespread phenomenon among prokaryotic viruses that is required to fulfill the biosynthetic needs of virion production. In this review we provide an overview of the most significant recent findings regarding virus-induced reprogramming of prokaryotic metabolism and suggest how quantitative systems biology approaches may be used to provide a holistic understanding of metabolic remodeling during lytic viral infection.


Assuntos
Vírus , Células Procarióticas
7.
Proc Natl Acad Sci U S A ; 120(23): e2220014120, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37252985

RESUMO

It has recently become appreciated that cells self-organize their interiors through the formation of biomolecular condensates. These condensates, typically formed through liquid-liquid phase separation of proteins, nucleic acids, and other biopolymers, exhibit reversible assembly/disassembly in response to changing conditions. Condensates play many functional roles, aiding in biochemical reactions, signal transduction, and sequestration of certain components. Ultimately, these functions depend on the physical properties of condensates, which are encoded in the microscopic features of the constituent biomolecules. In general, the mapping from microscopic features to macroscopic properties is complex, but it is known that near a critical point, macroscopic properties follow power laws with only a small number of parameters, making it easier to identify underlying principles. How far does this critical region extend for biomolecular condensates and what principles govern condensate properties in the critical regime? Using coarse-grained molecular-dynamics simulations of a representative class of biomolecular condensates, we found that the critical regime can be wide enough to cover the full physiological range of temperatures. Within this critical regime, we identified that polymer sequence influences surface tension predominately via shifting the critical temperature. Finally, we show that condensate surface tension over a wide range of temperatures can be calculated from the critical temperature and a single measurement of the interface width.


Assuntos
Condensados Biomoleculares , Ácidos Nucleicos , Proteínas/metabolismo , Ácidos Nucleicos/metabolismo , Organelas/metabolismo , Propriedades de Superfície
8.
Proc Natl Acad Sci U S A ; 119(30): e2113912119, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35857871

RESUMO

Studies of active matter-systems consisting of individuals or ensembles of internally driven and damped locomotors-are of interest to physicists studying nonequilibrium dynamics, biologists interested in individuals and swarm locomotion, and engineers designing robot controllers. While principles governing active systems on hard ground or within fluids are well studied, another class of systems exists at deformable interfaces. Such environments can display mixes of fluid-like and elastic features, leading to locomotor dynamics that are strongly influenced by the geometry of the surface, which, in itself, can be a dynamical entity. To gain insight into principles by which locomotors are influenced via a deformation field alone (and can influence other locomotors), we study robot locomotion on an elastic membrane, which we propose as a model of active systems on highly deformable interfaces. As our active agent, we use a differential driven wheeled robotic vehicle which drives straight on flat homogeneous surfaces, but reorients in response to environmental curvature. We monitor the curvature field-mediated dynamics of a single vehicle interacting with a fixed deformation as well as multiple vehicles interacting with each other via local deformations. Single vehicles display precessing orbits in centrally deformed environments, while multiple vehicles influence each other by local deformation fields. The active nature of the system facilitates a differential geometry-inspired mathematical mapping from the vehicle dynamics to those of test particles in a fictitious "spacetime," allowing further understanding of the dynamics and how to control agent interactions to facilitate or avoid multivehicle membrane-induced cohesion.


Assuntos
Locomoção , Robótica , Humanos
9.
Proc Natl Acad Sci U S A ; 119(1)2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983851

RESUMO

The viscoelectric effect concerns the increase in viscosity of a polar liquid in an electric field due to its interaction with the dipolar molecules and was first determined for polar organic liquids more than 80 y ago. For the case of water, however, the most common polar liquid, direct measurement of the viscoelectric effect is challenging and has not to date been carried out, despite its importance in a wide range of electrokinetic and flow effects. In consequence, estimates of its magnitude for water vary by more than three orders of magnitude. Here, we measure the viscoelectric effect in water directly using a surface force balance by measuring the dynamic approach of two molecularly smooth surfaces with a controlled, uniform electric field between them across highly purified water. As the water is squeezed out of the gap between the approaching surfaces, viscous damping dominates the approach dynamics; this is modulated by the viscoelectric effect under the uniform transverse electric field across the water, enabling its magnitude to be directly determined as a function of the field. We measured a value for this magnitude, which differs by one and by two orders of magnitude, respectively, from its highest and lowest previously estimated values.

10.
Nano Lett ; 24(26): 8024-8029, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38833525

RESUMO

Upon the interaction of light with metals, nonthermal electrons are generated with intriguing transient behavior. Here, we present femtosecond hot electron probing in a noveloptical pump/plasmon probe scheme. With this, we probed ultrafast interband and intraband dynamics with 15 nm interface selectivity, observing a two-component-decay of hot electron populations. Results are in good agreement with a three-temperature model of the metal; thus, we could attribute the fast (∼100 fs) decay to the thermalization of hot electrons and the slow (picosecond) decay to electron-lattice thermalization. Moreover, we could modulate the transmission of our plasmonic channel with ∼40% depth, hinting at the possibility of ultrafast information processing applications with plasmonic signals.

11.
Stroke ; 55(3): 696-704, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38406850

RESUMO

BACKGROUND: Dose response has remained a priority area in motor rehabilitation research for decades, prompting several large randomized trials and meta-analyses. These between-subjects comparisons have revealed equivocal relationships between the duration of motor practice and rehabilitation response. Prior reliance on time-consuming clinical assessments made it infeasible to capture within-subjects dose response, as tracking the dose-response trajectory of an individual requires dozens of repeated administrations. METHODS: This secondary observational cohort analysis of existing data from the gaming arms of the VIGoROUS multisite trial (Video Game Rehabilitation for Outpatient Stroke) describes the rehabilitation dose response of 80 participants with mild-moderate chronic stroke. The 3-dimensional joint position data were captured via the Kinect v2 optical sensor as participants completed a prescribed 15 hours of in-home unsupervised game-based motor practice. Kinematic dose response trajectories were fitted from hundreds to thousands of in-game repetitions for 4 separate upper extremity movements for each participant. RESULTS: Of 75 participants with sufficient data for dose-response analysis, 85% showed improved motor capacity for at least 1 movement. Dose response was bimodal; 42% required <5 hours of motor practice before reaching a plateau in movement kinematics, whereas 55% required >10 and 34% required >30 hours. We could predict with 93% accuracy whether or not an individual would ultimately respond to game-based motor practice within 5 hours of gameplay. CONCLUSIONS: Dose response varies considerably between individuals. About half of chronic stroke patients benefit from higher doses of motor practice than the current standard of care. Individualized dose-response data from motion capture rehabilitation gaming can guide clinical decision-making early on in treatment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02631850.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Extremidade Superior , Acidente Vascular Cerebral/terapia , Braço , Movimento/fisiologia , Fenômenos Biomecânicos , Recuperação de Função Fisiológica
12.
Rep Prog Phys ; 87(5)2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38518358

RESUMO

Single and collective cell migration are fundamental processes critical for physiological phenomena ranging from embryonic development and immune response to wound healing and cancer metastasis. To understand cell migration from a physical perspective, a broad variety of models for the underlying physical mechanisms that govern cell motility have been developed. A key challenge in the development of such models is how to connect them to experimental observations, which often exhibit complex stochastic behaviours. In this review, we discuss recent advances in data-driven theoretical approaches that directly connect with experimental data to infer dynamical models of stochastic cell migration. Leveraging advances in nanofabrication, image analysis, and tracking technology, experimental studies now provide unprecedented large datasets on cellular dynamics. In parallel, theoretical efforts have been directed towards integrating such datasets into physical models from the single cell to the tissue scale with the aim of conceptualising the emergent behaviour of cells. We first review how this inference problem has been addressed in both freely migrating and confined cells. Next, we discuss why these dynamics typically take the form of underdamped stochastic equations of motion, and how such equations can be inferred from data. We then review applications of data-driven inference and machine learning approaches to heterogeneity in cell behaviour, subcellular degrees of freedom, and to the collective dynamics of multicellular systems. Across these applications, we emphasise how data-driven methods can be integrated with physical active matter models of migrating cells, and help reveal how underlying molecular mechanisms control cell behaviour. Together, these data-driven approaches are a promising avenue for building physical models of cell migration directly from experimental data, and for providing conceptual links between different length-scales of description.


Assuntos
Desenvolvimento Embrionário , Modelos Biológicos , Movimento Celular/fisiologia
13.
Am J Physiol Heart Circ Physiol ; 326(1): H96-H102, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37921668

RESUMO

Wavelet analysis (WA) provides superior time-frequency decomposition of complex signals than conventional spectral analysis tools. To illustrate its usefulness in assessing transient phenomena, we applied a custom-developed WA algorithm to laser-Doppler (LD) signals of the cutaneous microcirculation measured at glabrous (finger pulp) and nonglabrous (forearm) sites during early recovery after dynamic exercise. This phase, importantly contributing to the establishment of thermal homeostasis after exercise cessation, has not been adequately explored because of its complex, transient form. Using WA, we decomposed the LD signals measured during the baseline and early recovery into power spectra of characteristic frequency intervals corresponding to endothelial nitric oxide (NO)-dependent, neurogenic, myogenic, respiratory, and cardiac physiological influence. Assessment of relative power (RP), defined as the ratio between the median power in the frequency interval and the median power of the total spectrum, revealed that endothelial NO-dependent (5.87 early recovery; 1.53 baseline; P = 0.005; Wilcoxon signed-rank test) and respiratory (0.71 early recovery; 0.40 baseline; P = 0.001) components were significantly increased, and myogenic component (1.35 early recovery; 1.83 baseline; P = 0.02) significantly decreased during early recovery in the finger pulp. In the forearm, only the RP of the endothelial NO-dependent (1.90 early recovery; 0.94 baseline; P = 0.009) component was significantly increased. WA presents an irreplaceable tool for the assessment of transient phenomena. The relative contribution of the physiological mechanisms controlling the microcirculatory response in the early recovery phase appears to differ in glabrous and nonglabrous skin when compared with baseline; moreover, the endothelial NO-dependent influence seems to play an important role.NEW & NOTEWORTHY We address the applicability of wavelet analysis (WA) in evaluating transient phenomena on a model of early recovery to exercise, which is the only exercise-associated phase characterized by a distinct transient shape and as such cannot be assessed using conventional tools. Our WA-based algorithm provided a reliable spectral decomposition of laser-Doppler (LD) signals in early recovery, enabling us to speculate roughly on the mechanisms involved in the regulation of skin microcirculation in this phase.


Assuntos
Exercício Físico , Pele , Microcirculação/fisiologia , Dedos , Homeostase , Fluxometria por Laser-Doppler , Análise de Ondaletas , Fluxo Sanguíneo Regional/fisiologia
14.
Small ; : e2400306, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934325

RESUMO

This paper describes how macroscopic stirring of a reaction mixture can be used to produce nanostructures exhibiting properties not readily achievable via other protocols. In particular, it is shown that by simply adjusting the stirring rate, a standard glutathione-based method-to date, used to produce only marginally stable fluorescent silver nanoclusters, Ag NCs-can be boosted to yield nanoclusters retaining fluorescence for unprecedented periods of over 2 years. This enhancement derives not simply from increased homogenization of the reaction mixture but mainly from an appropriately timed delivery of oxygen from above the reaction mixture. In effect, oxygen serves as a reagent that dictates size, structure, stability, and functional properties of the growing nanoobjects.

15.
Respir Res ; 25(1): 135, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509592

RESUMO

INTRODUCTION: Computed tomography (CT) is routinely employed on the evaluation of dyspnea, yet limited data exist on its assessment of diaphragmatic muscle. This study aimed to determine the capability of CT in identifying structural changes in the diaphragm among patients with ultrasound-confirmed diaphragmatic dysfunction. METHODS: Diaphragmatic ultrasounds conducted between 2018 and 2021 at our center in Marseille, France, were retrospectively collected. Diaphragmatic pillars were measured on CT scans at the L1 level and the celiac artery. Additionally, the difference in height between the two diaphragmatic domes in both diaphragmatic dysfunction cases and controls was measured and compared. RESULTS: A total of 65 patients were included, comprising 24 with diaphragmatic paralysis, 13 with diaphragmatic weakness, and 28 controls. In the case group (paralysis and weakness) with left dysfunctions (n = 24), the CT thickness of the pillars at the level of L1 and the celiac artery was significantly thinner compared with controls (2.0 mm vs. 7.4 mm and 1.8 mm vs. 3.1 mm, p < 0.001 respectively). Significantly different values were observed for paralysis (but not weakness) in the right dysfunction subgroup (n = 15) (2.6 mm vs. 7.4 mm and 2.2 mm vs. 3.8 mm, p < 0.001 respectively, for paralysis vs. controls). Regardless of the side of dysfunction, a significant difference in diaphragmatic height was observed between cases and controls (7.70 cm vs. 1.16 cm and 5.51 cm vs. 1.16 cm, p < 0.001 for right and left dysfunctions, respectively). Threshold values determined through ROC curve analyses for height differences between the two diaphragmatic domes, indicative of paralysis or weakness in the right dysfunctions, were 4.44 cm and 3.51 cm, respectively. Similarly for left dysfunctions, the thresholds were 2.70 cm and 2.48 cm, respectively, demonstrating good performance (aera under the curve of 1.00, 1.00, 0.98, and 0.79, respectively). CONCLUSION: In cases of left diaphragmatic dysfunction, as well as in paralysis associated with right diaphragmatic dysfunction, CT revealed thinner pillars. Additionally, a notable increase in the difference in diaphragmatic height demonstrated a strong potential to identify diaphragmatic dysfunction, with specific threshold values.


Assuntos
Diafragma , Debilidade Muscular , Humanos , Diafragma/diagnóstico por imagem , Estudos Retrospectivos , Ultrassonografia/métodos , Paralisia , Tomografia Computadorizada por Raios X , Tomografia
16.
Chemphyschem ; 25(6): e202300622, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38259051

RESUMO

Interfacial phenomena linked to the behavior of bound water, organic solvents (co-sorbates, dispersion media), hydrogen, methane, acids/bases, and salts bound to various silicas, polymers, and carbon materials were analyzed vs. temperature and concentrations using 1 H NMR spectroscopy, differential scanning calorimetry (DSC) and other methods. The material characteristics were studied using microscopy, infrared spectroscopy (IR), small angle X-ray scattering (SAXS), and nitrogen adsorption. Confined space effects (CSE) result in enhanced freezing point depression (FPD) and stronger diminution of solvent activity and colligative properties of liquid mixtures in narrower pores. Short hydrophobic functionalities (≡Si-CH3 , =Si(CH3 )2 ) at a silica surface and the presence of nanopores result in differentiation of bound water into weakly (WAW, δH =0.2-2.0 ppm) and strongly (SAW, δH =4-6 ppm) associated waters of smaller solvent activity in smaller clusters located in narrower pores and unfrozen below a bulk freezing point. These effects are enhanced in hydrophobic dispersion media. Hydrophobic liquids could displace bound water into narrower pores inaccessible for their molecules larger than water and/or into broader pores to reduce contact area between immiscible liquids. The observed phenomena depend on sorbent/sorbate kinds and play an important role on practical applications of various sorbents.

17.
Biotechnol Bioeng ; 121(2): 655-669, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38031493

RESUMO

A physics-based model for predicting cell culture fluid properties inside a stirred tank bioreactor with embedded PID controller logic is presented. The model evokes a time-accurate solution to the fluid velocity field and overall volumetric mass transfer coefficient, as well as the ongoing effects of interfacial mass transfer, species mixing, and aqueous chemical reactions. The modeled system also includes a direct coupling between process variables and system control variables via embedded controller logic. Satisfactory agreement is realized between the model prediction and measured bioreactor data in terms of the steady-state operating conditions and the response to setpoint changes. Simulation runtimes are suitable for industrial research and design timescales.


Assuntos
Reatores Biológicos , Oxigênio , Oxigênio/química , Técnicas de Cultura de Células , Simulação por Computador , Concentração de Íons de Hidrogênio
18.
Mol Pharm ; 21(2): 513-534, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38127789

RESUMO

Dissolution of ionizable drugs and their salts is a function of drug surface solubility driven by the surface pH, i.e., the microenvironmental pH at the solid/liquid interface, which will deviate from bulk pH when there is an acid-base reaction occurring at the solid/liquid interface. In this work, we first present a brief overview of the modeling approaches available in the literature, classified according to the rate-determining step assumed in the dissolution process. In the second part, we present and evaluate the prediction performance of two different modeling approaches for surface pH. The first method relies only on thermodynamic equilibria, while the second method accounts for transport phenomena of charged compounds through the diffusional boundary layer using the Nernst - Planck equation. Model outcomes are compared with experimental data taken from the literature and obtained during this work. In terms of surface pH predictions, the models provide identical values for weak acids or weak bases. The models' outcomes for bases are in good agreement with experimental data in acidic conditions (bulk pH 1-4), while overpredictions are observed in the 5-7 bulk pH range in a system-dependent manner. Deviations can be related to the effect of surface dissolution (also referred to as surface reaction), which may become a controlling mechanism and slow the replenishment of the unionized drug at the surface of the crystal. Surface pH predictions for acids are generally in good agreement with experiments, with a slight underestimation for some drug examples, which could be related to errors in intrinsic solubility determination or to the assumption of thermodynamic equilibrium at the surface of the drug. A good agreement is also observed for salts with the thermodynamic model except for mesylate salts, suggesting that other phenomena, not currently included in the thermodynamic equilibrium model, may determine the surface pH.


Assuntos
Sais , Concentração de Íons de Hidrogênio , Difusão , Solubilidade
19.
Cephalalgia ; 44(3): 3331024231209326, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38529897

RESUMO

PURPOSE: Visual snow syndrome comprises a whole-field static-like visual disturbance, with increased awareness of entopic phenomena, an inability to suppress the 'just seen' and photophobia. Visual snow syndrome is often associated with other problems such as headache, tinnitus, and anxiety. The earliest reported case of a patient experiencing symptoms consistent with visual snow syndrome dates only to 1995. This paper seeks to find patterns of experience in the medical literature of the past that are reminiscent of visual snow syndrome, to challenge the view that it is in any sense a novel disorder. Descriptions of subjective visual sensations such as experienced by patients suffering from visual snow syndrome were sought in treatises, textbooks and other literature generated by leading figures in 19th-century ophthalmology, physiology and physics. CONCLUSION: While retrospective diagnosis of modern illness categories in historical medical literature is an enterprise fraught with pitfalls, it is nonetheless possible to see patterns of experience in the 19th-century medical literature that are strongly reminiscent of visual snow syndrome.


Assuntos
Transtornos da Percepção , Transtornos da Visão , Humanos , Estudos Retrospectivos , Transtornos da Visão/complicações , Transtornos da Percepção/complicações , Fotofobia , Cefaleia/complicações
20.
J Exp Biol ; 227(5)2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38269528

RESUMO

Characterizing mechanisms of vocal production provides important insight into the ecology of acoustic divergence. In this study, we characterized production mechanisms of two types of vocalizations emitted by western harvest mice (Reithrodontomys megalotis), a species uniquely positioned to inform trait evolution because it is a sister taxon to peromyscines (Peromyscus and Onychomys spp.), which use vocal fold vibrations to produce long-distance calls, but more ecologically and acoustically similar to baiomyines (Baiomys and Scotinomys spp.), which employ a whistle mechanism. We found that long-distance calls (∼10 kHz) were produced by airflow-induced vocal fold vibrations, whereas high-frequency quavers used in close-distance social interactions (∼80 kHz) were generated by a whistle mechanism. Both production mechanisms were facilitated by a characteristic laryngeal morphology. Our findings indicate that the use of vocal fold vibrations for long-distance communication is widespread in reithrodontomyines (Onychomys, Peromyscus, Reithrodontomys spp.) despite overlap in frequency content that characterizes baiomyine whistled vocalizations. The results illustrate how different production mechanisms shape acoustic variation in rodents and contribute to ecologically relevant communication distances.


Assuntos
Laringe , Peromyscus , Animais , Sigmodontinae , Acústica , Ecologia
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