Single Extinction Research Articles

Single particle extinction and scattering optical method unveils in real time the influence of the blood components on polymeric nanoparticles

Here we report the quantitative in situ characterization of size distribution evolution of polymeric nanoparticles incubated in murine serum, filtered and unfiltered murine blood. We used an analytical optical approach, named Single Particle Extinction and Scattering (SPES), which relies on the measurements of two independent parameters of single particles. SPES is based on a robust self-reference interference optical scheme which allows a rejection of the spurious signals coming from the background caused by the medium. We employed polystyrene nanoparticles as reference system and polydisperse poly(lactic-co-glycolic acid) nanoparticles. Our results demonstrate that SPES can be used for carrying out ex vivo analysis of nanoparticles to evaluate the modifications that NPs undergo in vivo following different routes of entry. Conversely, Dynamic Light Scattering is not able to provide reliable results for these systems due to the presence of the biological components in solution.

Effect of N-acetylcysteine on motivation, seeking and relapse to ethanol self-administration.

Alcohol use disorder is a chronic and highly relapsing disorder, characterized by a loss of control over alcohol consumption and craving. Several studies suggest a key role of glutamate in this disorder. In recent years, the modulation of cystine/glutamate exchange via the xc- system has emerged as a new therapeutic alternative for reducing the excitatory glutamatergic transmission observed after ethanol self-administration in both rats and humans. The objective of this study was to determine whether a treatment with N-acetylcysteine (NAC), a cystine prodrug, could reduce ethanol self-administration, ethanol-seeking behavior and reacquisition of ethanol self-administration. Male Long Evans rats were trained to self-administer 20percent ethanol in operant cages for several weeks. Once the consumption surpassed 1g of ethanol/kg body weight/15minutes, the effect of an acute intraperitoneal injection of NAC (0, 25, 50 or 100mg/kg) 1hour before the beginning of each test was evaluated on different aspects of the operant self-administration behavior. We demonstrated antimotivational properties of NAC (100mg/kg), as ethanol-reinforced responding was reduced in a fixed ratio (-35percent) and in a progressive ratio schedule (-81percent). NAC also reduced ethanol-seeking behavior (-77percent) evaluated as extinction responding in a single extinction session. NAC was able to reduce reacquisition in rats that were abstinent for 17days, while NAC had no effect on ethanol relapse in rats previously exposed to six extinction sessions. Overall, our results demonstrate that NAC limits motivation, seeking behavior and reacquisition in rats, making it a potential new treatment for the maintenance of abstinence.

Characterization of single airborne particle extinction using the tunable optical trap-cavity ringdown spectroscopy (OT-CRDS) in the UV.

We integrated a rigid optical trap into a tunable pulsed cavity ringdown spectroscopy (OT-CRDS) system to characterize the extinction of single airborne particles in the UV spectral region (306-315 nm). Single solid particles from a multi-walled carbon nanotube (MWCNT), Bermuda grass smut spore, carbon microsphere, and blackened polyethylene microsphere were trapped in air based on the photophoretic force. The improved OT-CRDS system was highly sensitive and able to resolve extinctions of single particles from different materials and sizes at a given wavelength. Further, we successfully manipulated the number of particles, e.g., 1, 2 or more particles, in the trap and measured their distinguishable extinctions using the OT-CRDS. We also show that the particle size and extinction have a good linear correlation from the measurements of 24 single MWCNT particles. Material- and wavelength-dependent extinctions of the four types of airborne particles were also characterized. Results reveal that single airborne particles regardless of their differences in material and size, due to their heterogeneous morphology, have individual-particle dependent extinctions and that dependence can be resolved and characterized using the OT-CRDS technique.

Detecting the shape of anisotropic gold nanoparticles in dispersion with single particle extinction and scattering.

The shape and size of nanoparticles are important parameters affecting their biodistribution, bioactivity, and toxicity. The high-throughput characterisation of the nanoparticle shape in dispersion is a fundamental prerequisite for realistic in vitro and in vivo evaluation, however, with routinely available bench-top optical characterisation techniques, it remains a challenging task. Herein, we demonstrate the efficacy of a single particle extinction and scattering (SPES) technique for the in situ detection of the shape of nanoparticles in dispersion, applied to a small library of anisotropic gold particles, with a potential development for in-line detection. The use of SPES paves the way to the routine quantitative analysis of nanoparticles dispersed in biologically relevant fluids, which is of importance for the nanosafety assessment and any in vitro and in vivo administration of nanomaterials.

A Comprehensive Brownian Dynamics-Based Forward Model for Analytical (Ultra)Centrifugation

In this study, it is demonstrated how Brownian dynamics (BD) simulations can be used as a comprehensive forward model for analytical ultracentrifugation (AUC) and analytical centrifugation experiments. BD simulations are a versatile alternative to the numerical solution of Lamm's equation. Time dependent concentration profiles can be accurately predicted by means of the BD simulations even for colloidal systems with multiple species. It is shown that in combination with Mie's theory for light scattering, BD simulations can be extended to generate data mimicking a multiwavelength detector for AUC. The forward model can be utilized as a comprehensive tool for developing and testing sophisticated data analyzing tools that can enhance the capabilities of using centrifugation-based techniques for characterizing nanoparticles. The model is validated using common analysis tools developed for the evaluation of sedimentation velocity data generated by a single wavelength extinction detector. The accuracy of the code is also proved using the recently developed and highly versatile High Dynamic Range-MULTIwavelength FITting tool for accurately predicting particle size distributions via gravitational sweep experiments performed in AUCs equipped with multiwavelength detectors.

One month of cocaine abstinence potentiates rapid dopamine signaling in the nucleus accumbens core

Cocaine addiction is a chronic relapsing disorder that is difficult to treat in part because addicts relapse even after extended periods of abstinence. Given the importance of the mesolimbic dopamine (DA) system in drug addiction, we sought to characterize cocaine abstinence induced changes in rapid DA signaling in the nucleus accumbens (NAc). Here, rats were trained to self-administer cocaine for 14 consecutive days, then divided into two groups. Day 1 rats (D1; n = 7) underwent 24 h of abstinence; Day 30 rats (D30; n = 7) underwent one month of abstinence. After abstinence, all rats underwent a single extinction session. Immediately after, rats were deeply anesthetized and fast scan cyclic voltammetry (FSCV) was used to measure DA release and uptake dynamics in the NAc core before and following a single cocaine injection. We show that one month of cocaine abstinence potentiates the peak concentration of electrically evoked DA in the NAc core following an acute injection of cocaine. This potentiation is not related to alterations in DA uptake parameters, which are unchanged following abstinence, but may reflect alterations in release. These results further support the abundance of literature showing that cocaine abstinence induces neuroplasticity in brain areas implicated in drug reward and relapse. The present findings also demonstrate critical differences between abstinence-induced neuroadaptations in DA signaling and those caused by drug exposure itself.

Shape and size constraints on dust optical properties from the Dome C ice core, Antarctica.

Mineral dust aerosol (dust) is widely recognized as a fundamental component of the climate system and is closely coupled with glacial-interglacial climate oscillations of the Quaternary period. However, the direct impact of dust on the energy balance of the Earth system remains poorly quantified, mainly because of uncertainties in dust radiative properties, which vary greatly over space and time. Here we provide the first direct measurements of the aerosol optical thickness of dust particles windblown to central East Antarctica (Dome C) during the last glacial maximum (LGM) and the Holocene. By applying the Single Particle Extinction and Scattering (SPES) technique and imposing preferential orientation to particles, we derive information on shape from samples of a few thousands of particles. These results highlight that clear shape variations occurring within a few years are hidden to routine measurement techniques. With this novel measurement method the optical properties of airborne dust can be directly measured from ice core samples, and can be used as input into climate model simulations. Based on simulations with an Earth System Model we suggest an effect of particle non-sphericity on dust aerosol optical depth (AOD) of about 30% compared to spheres, and differences in the order of ~10% when considering different combinations of particles shapes.

Measuring shape and size of micrometric particles from the analysis of the forward scattered field

Characterizing nano- and micro-particles in fluids still proves to be a significant challenge for both science and industry. Here, we show how to determine shape and size distributions of polydisperse water suspensions of micron-sized particles by the analysis of the field scattered in the forward direction by single particles illuminated by a laser beam. We exploit the novel Single Particle Extinction and Scattering method in connection with shear conditions which give preferred orientations to the particles passing through the scattering volume. Water suspensions of calibrated non-spherical particles, polydisperse standard monophasic mineral samples of quartz and kaolinite, and a mixture of quartz and illite are studied in detail. Application and limitation of the method are discussed.

Instantaneous shrinking and single point extinction for viscous Hamilton–Jacobi equations with fast diffusion

For a large class of non-negative initial data, the solutions to the quasilinear viscous Hamilton-Jacobi equation $\partial_t u-\Delta_p u+|\nabla u|^q=0$ in $(0,\infty)\times\real^N$ are known to vanish identically after a finite time when $2N/(N+1) 0$, the positivity set of $u(t)$ is a bounded subset of $\real^N$ even if $u_0 > 0$ in $\real^N$. This decay condition on $u_0$ is also shown to be optimal by proving that the positivity set of any solution emanating from a positive initial condition decaying at a slower rate as $|x|\to\infty$ is the whole $\real^N$ for all times. The time evolution of the positivity set is also studied: on the one hand, it is included in a fixed ball for all times if it is initially bounded (\emph{localization}). On the other hand, it converges to a single point at the extinction time for a class of radially symmetric initial data, a phenomenon referred to as \emph{single point extinction}. This behavior is in sharp contrast with what happens when $q$ ranges in $[p-1,p/2)$ and $p\in (2N/(N+1),2]$ for which we show \emph{complete extinction}. Instantaneous shrinking and single point extinction take place in particular for the semilinear viscous Hamilton-Jacobi equation when $p=2$ and $q\in (0,1)$ and seem to have remained unnoticed.

Efectos del cambio climático sobre especies de plantas vasculares del sur de los Andes Centrales: un estudio en el noroeste de Argentina (NOA)

The Tropical Andes region has been indicated as a highly vulnerable region to climate change for its high diversity and endemism and its great altitudinal variability. While there have been an important number of predictions about the changing climate in the region, few studies have evaluated the impact this will have on the distribution of species. In this paper, we estimated the effect of climate change on the distribution and conservation of endemic species from north-western Argentina (southernmost Central Andes) for the years 2050 and 2080 and under two future scenarios (A2 and B1). According to the results, from the present to 2080, climate change in the region will cause a single extinction event, and changes in all distributional ranges of endemic species. Moreover, a widespread displacement of endemic species towards higher altitudes and subtropical areas is predicted, indicating that the impacts of future climate change will be greater for low and less arid ecoregions. Moreover, the NOA system of protected areas would not be able to represent adequately the endemic flora in the future under any scenario, according to the established target in the present study. These results highlight the need to concentrate conservation efforts on those species and ecosystems identified here as the most vulnerable in order to ensure the future conservation of the endemic flora of the most southern part of the Central Andes.

Retrieval of aerosol parameters from multiwavelength lidar: investigation of the underlying inverse mathematical problem

We present an investigation of some important mathematical and numerical features related to the retrieval of microphysical parameters [complex refractive index, single-scattering albedo, effective radius, total number, surface area, and volume concentrations] of ambient aerosol particles using multiwavelength Raman or high-spectral-resolution lidar. Using simple examples, we prove the non-uniqueness of an inverse solution to be the major source of the retrieval difficulties. Some theoretically possible ways of partially compensating for these difficulties are offered. For instance, an increase in the variety of input data via combination of lidar and certain passive remote sensing instruments will be helpful to reduce the error of estimation of the complex refractive index. We also demonstrate a significant interference between Aitken and accumulation aerosol modes in our inversion algorithm, and confirm that the solutions can be better constrained by limiting the particle radii. Applying a combination of an analytical approach and numerical simulations, we explain the statistical behavior of the microphysical size parameters. We reveal and clarify why the total surface area concentration is consistent even in the presence of non-unique solution sets and is on average the most stable parameter to be estimated, as long as at least one extinction optical coefficient is employed. We find that for selected particle size distributions, the total surface area and volume concentrations can be quickly retrieved with fair precision using only single extinction coefficients in a simple arithmetical relationship.

Single particle optical extinction and scattering allows real time quantitative characterization of drug payload and degradation of polymeric nanoparticles.

The behavior of nanoparticles in biological systems is determined by their dimensions, size distribution, shape, surface chemistry, density, drug loading and stability; the characterization of these parameters in realistic conditions and the possibility to follow their evolution in vitro and in vivo are, in most of the cases, far from the capabilities of the standard characterization technologies. Optical techniques such as dynamic light scattering (DLS) are, in principle, well suited for in line characterization of nanoparticle, however their fail in characterizing the evolution of nanoparticle in solution where change in particle dimension and density is present. Here we present an in-line optical technique based on single particle extinction and scattering (SPES) overcoming the limitations typical of DLS and allowing for the efficient characterization of nanoparticle polydispersity, index of refraction and degradation dynamics in solution. Using SPES, we characterized the evolution of PLGA nanoparticles with different structures and drug payloads in solution and we compared the results with DLS. Our results suggest that SPES could be used as a process analytical technology for pharmaceutical nanoparticle production.

Optical trap-cavity ringdown spectroscopy as a single-aerosol-particle-scope

We report a single-aerosol-particle-scope using an optical trapping-cavity ringdown spectroscopy technique. The scope can not only view physical parameters such as size, motion, and restoring force constant of a single aerosol particle trapped in air but also display time-, particle-, or wavelength-resolved chemical properties such as single aerosol particle extinction. We demonstrate the scope by trapping and walking single carbon-nanotube particles of ∼50 μm in size and viewing those properties via changes of ringdown time. This single-aerosol-particle-scope offers a powerful tool to study both physical and chemical properties as well as their evolving dynamics.

Direct probing of anode arc root dynamics and voltage instability in a dc non-transferred arc plasma jet

The transient dynamics of the anode arc root in a dc non-transferred arc plasma torch is captured through fast photography and directly correlated with the associated voltage instability for the first time. The coexistence of multiple arc roots, the transition to a single arc root, root formation and extinction are investigated for the steady, takeover and re-strike modes of the arc. Contrary to the usual concept, the emerging plasma jet of a dc non-transferred arc plasma torch is found to carry current. An unusually long self-propelled arc plasma jet, a consequence of the phenomenon, is demonstrated.

End-Triassic nonmarine biotic events

The Late Triassic was a prolonged interval of elevated extinction rates and low origination rates that manifested themselves in a series of extinctions during Carnian, Norian and Rhaetian time. Most of these extinctions took place in the marine realm, particularly affecting radiolarians, conodonts, bivalves, ammonoids and reef-building organisms. On land, the case for a Late Triassic mass extinction is much more tenuous and has largely focused on tetrapod vertebrates (amphibians and reptiles), though some workers advocate a sudden end-Triassic (TJB) extinction of land plants. Nevertheless, an extensive literature does not identify a major extinction of land plants at the TJB, and a comprehensive review of palynological records concluded that TJB vegetation changes were non-uniform (different changes in different places), not synchronous and not indicative of a mass extinction of land plants. Claims of a substantial perturbation of plant ecology and diversity at the TJB in East Greenland are indicative of a local change in the paleoflora largely driven by lithofacies changes resulting in changing taphonomic filters. Plant extinctions at the TJB were palaeogeographically localized events, not global in extent. With new and more detailed stratigraphic data, the perceived TJB tetrapod extinction is mostly an artifact of coarse temporal resolution, the compiled correlation effect. The amphibian, archosaur and synapsid extinctions of the Late Triassic are not concentrated at the TJB, but instead occur stepwise, beginning in the Norian and extending into the Hettangian. There was a disruption of the terrestrial ecosystem across the TJB, but it was more modest than generally claimed. The ecological severity of the end-Triassic nonmarine biotic events are relatively low on the global scale. Biotic turnover at the end of the Triassic was likely driven by the CAMP (Central Atlantic Magmatic Province) eruptions, which caused significant environmental perturbations (cooling, warming, acidification) through outgassing, but the effects on the nonmarine biota appear to have been localized, transient and not catastrophic. Long-term changes in the terrestrial biota across the TJB are complex, diachronous and likely climate driven evolutionary changes in the context of fluctuating background extinction rates, not a single, sudden or mass extinction.

Adolescent-onset of cocaine use is associated with heightened stress-induced reinstatement of cocaine seeking.

Adolescent rats take cocaine more readily than adults, are more sensitive to lower doses of the drug and work harder for it. It remains unknown if adolescent-onset of cocaine use has long-term consequences on adult relapse liability. Therefore, we tested if self-administering cocaine during adolescence impacts subsequent stress-induced reinstatement to cocaine seeking and taking, after a prolonged drug-free period. Adolescent (~P42) or adult (P88) rats self-administered cocaine (0.6 or 1.2 mg/kg/infusion) for 7 or 10 days. Then, they underwent a prolonged drug-free period (21-40 days), after which they were tested for reinstatement of cocaine-seeking (i.e. responding in the absence of cocaine) induced by the stress hormone corticosterone, the pharmacological stressor yohimbine or electric footshock. Studies employed either single extinction session (within-session extinction/reinstatement) or repeated extinction prior to reinstatement (between-session extinction/reinstatement). Finally, in a separate set of experiments, rats underwent a prolonged drug-free period (~40 days) and were then allowed to self-administer cocaine again, using progressive-ratio procedures that appraise the reinforcing efficacy of cocaine. Rats with adolescent-onset of cocaine use showed greater stress-induced reinstatement of cocaine seeking than rats with adult-onset of cocaine use. This was observed across conditions, providing external validity to these results. Groups did not differ on drug taking in progressive-ratio tests. Our studies indicate that experiencing cocaine during adolescence renders subjects particularly responsive to the subsequent effects of stress on drug seeking. This heightened propensity for reinstatement puts adolescent-onset drug users at heightened risk for relapse.

L-type Ca²⁺ channel blockade with antihypertensive medication disrupts VTA synaptic plasticity and drug-associated contextual memory.

Drug addiction is driven, in part, by powerful and enduring memories of sensory cues associated with drug intake. As such, relapse to drug use during abstinence is frequently triggered by an encounter with drug-associated cues, including the drug itself. L-type Ca2+ channels (LTCCs) are known to regulate different forms of synaptic plasticity, the major neural substrate for learning and memory, in various brain areas. Long-term potentiation (LTP) of NMDA receptor (NMDAR)-mediated glutamatergic transmission in the ventral tegmental area (VTA) may contribute to the increased motivational valence of drug-associated cues triggering relapse. In this study, using rat brain slices, we found that isradipine, a general LTCC antagonist used as antihypertensive medication, not only blocks the induction of NMDAR LTP but also promotes the reversal of previously induced LTP in the VTA. In behaving rats, isradipine injected into the VTA suppressed the acquisition of cocaine-paired contextual cue memory assessed using a conditioned place preference (CPP) paradigm. Furthermore, administration of isradipine or a CaV1.3 subtype-selective LTCC antagonist (systemic or intra-VTA) before a single extinction or reinstatement session, while having no immediate effect at the time of administration, abolished previously acquired cocaine and alcohol (ethanol) CPP on subsequent days. Notably, CPP thus extinguished cannot be reinstated by drug re-exposure, even after 2 weeks of withdrawal. These results suggest that LTCC blockade during exposure to drug-associated cues may cause unlearning of the increased valence of those cues, presumably via reversal of glutamatergic synaptic plasticity in the VTA.

Direct measurements of the optical cross sections and refractive indices of individual volatile and hygroscopic aerosol particles.

We present measurements of the evolving extinction cross sections of individual aerosol particles (spanning 700-2500 nm in radius) during the evaporation of volatile components or hygroscopic growth using a combination of a single particle trap formed from a Bessel light beam and cavity ring-down spectroscopy. For single component organic aerosol droplets of 1,2,6-hexanetriol, polyethylene glycol 400, and glycerol, the slow evaporation of the organic component (over time scales of 1000 to 10,000 s) leads to a time-varying size and extinction cross section that can be used to estimate the refractive index of the droplet. Measurements on binary aqueous-inorganic aerosol droplets containing one of the inorganic solutes ammonium bisulfate, ammonium sulfate, sodium nitrate, or sodium chloride (over time scales of 1000 to 15,000 s) under conditions of changing relative humidity show that extinction cross-section measurements are consistent with expectations from accepted models for the variation in droplet refractive index with hygroscopic growth. In addition, we use these systems to establish an experimental protocol for future single particle extinction measurements. The advantages of mapping out the evolving light extinction cross-section of an individual particle over extended time frames accompanied by hygroscopic cycling or component evaporation are discussed.

Conodonts versus Triassic Climatic and Eustatic Changes

From astronomical, sedimentological, paleo-geographical and geochemical points of view, there is a general agreement that the Triassic period was exceptionally warm. The 51 MA long Triassic period started during the Siberian Traps and ended at the height of the Central Atlantic Magmatic Province activity. It is comprised between End Permian and End Triassic mass extinctions. Conodonts survived the former but got extinct by the end of the latter. Three major waves characterise the evolution of Triassic conodonts:I.The 5 MA long Scythian recovery by intensive speciation (23 S/MA);II.The 10 MA long Dinarian of intensive radiation (8.5 S/MA);III.The 16 MA long Julian - Lacian survival (2S/MA) and 20 MA of Alaunian – Rhaetian decline until extinction.The major causes of stress affecting the evolution of Triassic conodonts are environmental, such as marine regressions, anoxic episodes, and thermal or trophic (nutritional) stress. These stressful episodes caused dwarfing and extinction of larger forms (r-selection). Smaller forms with a short life span and rapid proliferation are the result of heterochrony such as proteromorphic retrogradation (Atavism).The disappearance of the conodonts was not caused by a single mass extinction event, but the result of summing up stress factors from hostile environments over a long time.

Exposure treatment in multiple contexts attenuates return of fear via renewal in high spider fearful individuals

Background and objectivesResearch has demonstrated that after exposure treatment, re-exposure to a previously feared stimulus outside of the treatment context can result in renewal of fear. The current study investigated whether conducting exposure treatment in multiple real-life contexts can attenuate renewal of fear. MethodsForty-six moderate to high spider fearful individuals were randomly allocated to groups that received exposure treatment in either one context or three contexts. Follow-up testing was conducted one week and four weeks after exposure in the treatment context or a novel context. ResultsRenewal of fear was found for the single extinction context group when exposed to the feared object in a novel context with self-report of fear, heart rate, and behavioural avoidance. However, renewal of fear was attenuated for the multiple extinction context group. LimitationsThe sample included moderate to high spider fearful participants rather than clients with spider phobia, potentially limiting the generalisability of the findings to clinical populations. ConclusionsUsing multiple extinction contexts in combination with other methods of attenuating renewal (e.g., context similarity) may provide a means to reduce the risk of renewal of fear.