Sunlight can convert atmospheric aerosols into a glassy solid state and modify their environmental impacts

Secondary organic aerosol (SOA) plays a critical, yet uncertain, role in air quality and climate. Once formed, SOA is transported throughout the atmosphere and is exposed to solar UV light. Information on the viscosity of SOA, and how it may change with solar UV exposure, is needed to accurately predict air quality and climate. However, the effect of solar UV radiation on the viscosity of SOA and the associated implications for air quality and climate predictions is largely unknown. Here, we report the viscosity of SOA after exposure to UV radiation, equivalent to a UV exposure of 6 to 14 d at midlatitudes in summer. Surprisingly, UV-aging led to as much as five orders of magnitude increase in viscosity compared to unirradiated SOA. This increase in viscosity can be rationalized in part by an increase in molecular mass and oxidation of organic molecules constituting the SOA material, as determined by high-resolution mass spectrometry. We demonstrate that UV-aging can lead to an increased abundance of aerosols in the atmosphere in a glassy solid state. Therefore, UV-aging could represent an unrecognized source of nuclei for ice clouds in the atmosphere, with important implications for Earth’s energy budget. We also show that UV-aging increases the mixing times within SOA particles by up to five orders of magnitude throughout the troposphere with important implications for predicting the growth, evaporation, and size distribution of SOA, and hence, air pollution and climate.

Secondary organic aerosol (SOA) represents a considerable mass fraction of atmospheric aerosol particles. SOA can directly affect climate by scattering shortwave radiation, or indirectly by acting as nuclei for cloud droplets and ice crystals (1–4). SOA also contributes to poor air quality in urban areas (5–9).SOA is often formed through the oxidation of anthropogenic and biogenic volatile organic compounds (VOCs), followed by gas-particle partitioning of the semivolatile and low-volatility oxidation products (10–12). Of the total mass of global VOCs, ∼90% originates from biogenic sources, with monoterpenes (C₁₀) being one of the most important types of biogenic VOCs (4, 10–12).Once formed in the atmosphere, SOA is transported throughout the troposphere (13–15). SOA has average lifetimes on the order of 1 to 2 wk (14,16), but can be considerably longer in the upper troposphere. During this atmospheric transport, SOA particles can undergo aging by multiple processes, including heterogeneous oxidation (17–19), aqueous phase photooxidation (20–23), photosensitized uptake of gases (24–27), and UV-aging (28–33). Aging processes can change the physicochemical properties of aerosols. For example, UV-aging was reported to decrease mass, increase the oxidation state, decrease the volatility, and decrease the light absorption and scattering ability of SOA particles (24, 28, 31, 34–37).To predict the importance of SOA for air pollution and climate, information on viscosity and diffusion rates within SOA particles is needed (38). Viscosity and diffusivity are inversely related as described with the Stokes-Einstein equation. Slower diffusion rates have been found to affect gas-particle partitioning and hence the evolution of mass and size distributions of SOA (39, 40). Molecular diffusion also affects rates and mechanisms of multiphase reactions within SOA, which in turn dictate SOA composition (41, 42) and long-range transport of pollutants such as polycyclic aromatic hydrocarbons (43–47). Viscous aerosols have been shown to create anoxic conditions as well as limit molecular motion, resulting in the stabilization of photochemically produced radicals, trapping them in the organic matrix (48, 49). Furthermore, the viscosity of SOA can impact their ability to act as cloud condensation nuclei (50) and ice nuclei (51). For example, if SOA particles are in a glassy solid state, defined as a material with a viscosity greater than 10¹² Pa s, they may act as heterogeneous ice nuclei in clouds (14, 52, 53).The viscosity of fresh, unaged SOA types has been reported in previous laboratory studies (54–58). In contrast, the viscosity of SOA material after aging has rarely been measured, and so far, no measurements of the SOA viscosity after UV exposure, hereafter referred to as UV-aging, have been reported. It is especially important to understand the effect of UV-aging on the viscosity of SOA in the upper troposphere, where particles can spend a long time interacting with solar radiation, and where the dry and low-temperature conditions in this part of the troposphere favor higher SOA viscosities. In addition to laboratory studies, recent modeling studies have used parameterizations based on viscosity measurements and glass transition temperatures to predict global distributions of viscosities and diffusion rates within SOA particles (40, 59–63). However, the effect of UV-aging on viscosity and diffusion rates within SOA was not explicitly considered in these studies. As a result, global distributions of viscosity and diffusion rates within SOA and associated atmospheric impacts remain highly uncertain.To address these important gaps in knowledge, we measured the viscosity of SOA after exposure to UV radiation with a wavelength (λ) of 305 nm for 12 d and compared it to viscosity of control SOA samples that remained in darkness for the same period of time. This exposure time corresponds to an equivalent exposure of 6 to 14 d at midlatitudes during the summer (64, 65). We show that such UV-aging leads to considerable increases in viscosity and mixing times of organic molecules within a SOA particle by as much as five orders of magnitude compared to the unirradiated SOA particles. We show that these increases can be explained, at least in part, by an increase in average molecular mass and an increase in average elemental oxygen-to-carbon ratio of the organic molecules constituting the SOA material, as determined by high-resolution mass spectrometry. The increased viscosity of aged SOA likely leads to increased abundance of SOA in a glassy solid state that can potentially act as ice nucleating particles, with implications for climate predictions. We also show that mixing times within 200 nm SOA particles by molecular diffusion can often be larger than 0.5 h for most parts of the free troposphere, contrary to the assumptions frequently used in chemical transport models, with important implications for predicting the growth, evaporation, and size distribution of SOA, and hence, air pollution and climate.     

Postoperative intravesical instillation of THP for superficial bladder tumor: clinical results of prophylactic effects on the recurrence. Fukushima THP Research Group]

Intravesical instillation of pirarubicin (THP) was performed on 66 patients with superficial bladder cancer after transurethral resection to evaluate the prophylactic effect against tumor recurrence. Intravesical chemotherapy was carried out at the concentration of 20mg/40ml. THP was initially instilled three times for one week, following instillation of every two weeks for ten times, and then every one month for seven times. Bladder irritability was demonstrated 21 of 66 cases (31.8%). Although there was a case of contracted bladder, generalized side effect was no case. Eligible cases for evaluation of efficacy were 43 out of 66 patients. The non-recurrence rate (by Kaplan-Meier's method) at one and two years were 90.4% and 77.8%, respectively. Intravesical THP instillation seems to be effective for the purpose of prophylaxis against the recurrence of superficial bladder tumor.     

Coexistence of three liquid phases in individual atmospheric aerosol particles

Individual atmospheric particles can contain mixtures of primary organic aerosol (POA), secondary organic aerosol (SOA), and secondary inorganic aerosol (SIA). To predict the role of such complex multicomponent particles in air quality and climate, information on the number and types of phases present in the particles is needed. However, the phase behavior of such particles has not been studied in the laboratory, and as a result, remains poorly constrained. Here, we show that POA+SOA+SIA particles can contain three distinct liquid phases: a low-polarity organic-rich phase, a higher-polarity organic-rich phase, and an aqueous inorganic-rich phase. Based on our results, when the elemental oxygen-to-carbon (O:C) ratio of the SOA is less than 0.8, three liquid phases can coexist within the same particle over a wide relative humidity range. In contrast, when the O:C ratio of the SOA is greater than 0.8, three phases will not form. We also demonstrate, using thermodynamic and kinetic modeling, that the presence of three liquid phases in such particles impacts their equilibration timescale with the surrounding gas phase. Three phases will likely also impact their ability to act as nuclei for liquid cloud droplets, the reactivity of these particles, and the mechanism of SOA formation and growth in the atmosphere. These observations provide fundamental information necessary for improved predictions of air quality and aerosol indirect effects on climate.

Atmospheric aerosols are airborne suspensions of microscopic particles and are a major contributor to poor air quality, which causes respiratory and cardiovascular disease and results in over 3 million premature deaths globally per year (1). Atmospheric aerosols also modify climate by scattering and absorbing solar radiation and by serving as nuclei for liquid cloud droplets (2) and ice crystals (3). To predict the impacts of aerosols on air quality and climate, information on the number and types of phases present in atmospheric particles is needed. This is because the number and types of phases govern important aerosol processes and properties including aerosol growth and evaporation, optical properties, reactivity, and the ability of aerosols to act as nuclei for liquid cloud droplets and ice crystals (3–13). Nevertheless, our understanding of the phase behavior of atmospheric aerosols is far from complete, resulting in large uncertainties when predicting aerosol effects on air quality and climate.A large fraction of atmospheric aerosols can be classified as primary organic aerosol (POA), secondary organic aerosol (SOA), and secondary inorganic aerosol (SIA). POA is emitted directly into the atmosphere. In contrast, SOA and SIA are formed in the atmosphere by gas and condensed-phase reactions. All three types of aerosols are abundant in and downwind of urban areas (14). Field measurements have also shown that POA, SOA, and SIA often become internally mixed in and downwind of urban areas (15–19). For example, Moffet and Prather (20) showed that primary aerosol particles are internally mixed with secondary aerosol on a timescale of 3 h in Riverside, United States, and Mexico City, Mexico. Cross et al. (21) showed that POA particles are internally mixed with secondary aerosol on a timescale of 30 min during mid to late morning in Mexico City, Mexico. Moreover, measurements by Vester et al. (18) showed that 20 to 40% of secondary aerosols are internally mixed with primary aerosols in the urban areas of Mainz, Germany. Mechanisms for the formation of these internally mixed particles include coagulation, gas–particle partitioning, cloud processing, and multiphase chemical reactions (5, 15, 22, 23). We refer to particles containing POA, SOA, and SIA as POA+SOA+SIA particles.Previous studies on the phase behavior of atmospheric particles have focused on pure SIA (24), pure SOA (10, 13), mixtures of POA and SOA (25–31), and mixtures of SOA and SIA (11, 32). These studies have often been carried out as a function of relative humidity (RH) since RH often cycles between low and high values in the atmosphere and since RH can impact the phase behavior of aerosol particles (11, 24, 32). Studies with mixtures of POA and SOA have shown that one or two liquid phases can form in individual particles, depending on the POA properties, SOA properties, and RH (25–31). Similarly, studies with mixtures of SOA and SIA revealed that one or two liquid phases can form depending on the SOA properties, SIA properties, and RH (11, 32). Surprisingly, in a recent study, three liquid phases were observed in some mixtures of SOA and SIA proxies (33). However, two liquid phases were reported in the majority of those experiments, and conditions favoring three liquid phases were unclear and not elucidated.The phase behavior of particles containing POA, SOA, and SIA have so far only been investigated using molecular dynamics simulations of nanoparticles less than 10 nm in diameter (34). Three separate chemically distinct domains were observed in these simulations, but laboratory studies are needed in order to confirm these predictions, especially for particles with larger diameters, which make up the vast majority of the mass of atmospheric particulate matter.In the current study, a solvatochromic dye and fluorescence microscopy are used to determine the phase behavior of POA+SOA+SIA particles as a function of RH. Although solvatochromic dyes have been used widely in biology and chemistry (e.g., ref 35), they have, so far, not been used to characterize the phase behavior of atmospheric aerosols. We demonstrate that POA+SOA+SIA particles can often contain three distinct liquid phases. In addition, thermodynamic equilibrium predictions and associated kinetic gas–aerosol simulations are used to quantify possible atmospheric implications of these experiments. We show that the coexistence of three liquid phases in POA+SOA+SIA particles impacts their equilibration timescales with the surrounding gas phase and likely their ability to act as nuclei for liquid cloud droplets, with possible implications for interpreting field studies and predicting aerosol effects on climate.     

Change in heart rate variability preceding ST elevation in a patient with vasospastic angina pectoris

Summary A case of vasospastic angina (VSA) in a 62-year-old man with frequent ST elevation throughout the day was reported. His coronary angiogram showed that intracoronary methylergometrine had induced total occlusion due to a vasospasm. Analysis by Holter monitoring suggested that the autonomic nervous system would contribute differently to the initiation of the coronary spasm depending on whether the VSA attacks occurred during the daytime or at night. During the nighttime, the high-frequency power (HF:0.15–0.4 Hz) decreased during the 2 min before ST elevation, and the heart rate increased immediately before ST elevation. The low-frequency power (LF: 0.04–0.15 Hz) and the ratio of LF to HF (LF/HF) did not significantly change before ST elevation. In contrast, each of the heart rate variability components and the heart rate did not significantly change before ST elevation during the daytime. Thus, the pathophysiology of VSA during the daytime and nighttime seems to be differents in its relation to autonomic tone. During the nighttime, vagal with-drawal may be a component of the mechanisms leading to VSA, while during the daytime, a change in autonomic tone may not play a major role in this case.     

Low cerebrospinal fluid-to-plasma ratios of orally administered lenalidomide mediated by its low cell membrane permeability in patients with hematologic malignancies

Annals of Hematology - Lenalidomide is a synthetic analog of thalidomide formed by the removal of one keto group (plus the addition of an amino group); it has anti-tumor activities beneficial for...     

The effects of temperature and scopolamine on N-methyl-D-aspartate antagonist-induced neuronal necrosis in the rat

The effects of temperature and scopolamine on dizocilpine maleate-induced neuronal necrosis in the rat cingulate/retrosplenial cortex, entorhinal/olfactory cortices and the dentate gyrus were studied. Mild, protracted hypothermia (48 h at a brain temperature of 34 degrees C), induced by a servo-controlled "exposure technique" in the awake female rat, significantly reduced dizocilpine maleate (5.0 mg/kg, i.p.)-induced neuronal death in the cingulate/retrosplenial and entorhinal/olfactory cortices seven days following drug administration. Scopolamine (0.25 mg/kg, i.p.), putatively neuroprotective [Olney J. W. et al. (1991) Science 254, 1515-1518], did not reduce injury in the cingulate/retrosplenial cortex of female rats following one injection, but did following two and three doses. Scopolamine had no significant effect in the other brain regions. A temperature elevation of only 1 degree C above baseline for 48 h in awake female rats increased dizocilpine maleate-induced damage. Finally, the sex differences in N-methyl-D-aspartate antagonist toxicity were replicated and extended to other structures, and found not to be due to temperature differences. Our data show that dizocilpine maleate neurotoxicity is temperature sensitive. Scopolamine treatment needed to be prolonged in order to reduce injury, and even then was only efficacious in one of three brain regions. The results underscore the importance of using neuronal necrosis in several brain regions as the endpoint and for the use of prolonged therapeutic interventions. Furthermore, given the potential hypothermic action of other putative neuroprotective drugs, a mechanistic re-evaluation of N-methyl-D-aspartate antagonist-induced injury is needed, with precise brain temperature measurement.     

Changing the adenovirus fiber for retaining gene delivery efficacy in the presence of neutralizing antibodies

Prior infection has primed most adult humans for a rapid neutralizing antibody (NAb) response when re-exposed to adenovirus. NAb induction can severely limit the efficacy of systemic re-administration of adenoviral gene therapy. We hypothesized that changing the fiber knob could overcome NAb. Immune-competent mice were exposed to serotype 5 adenovirus (Ad5)(GL), Ad5/3luc1, Ad5lucRGD or Ad5pK7(GL). Mice immunized with Ad5(GL) featured reduced intravenous Ad5(GL) gene transfer to most organs, including the liver, lung and spleen. Ad5(GL) gene transfer was affected much less by exposure to capsid-modified viruses. Anti-Ad5(GL) NAb blocked intravenous Ad5(GL) gene transfer to orthotopic lung cancer xenografts, whereas capsid-modified viruses were not affected. When gene transfer to fresh cancer and normal lung explants was analyzed, we found that capsid-modified viruses allowed effective gene delivery to tumors in the presence of anti-Ad5(GL) NAb, whereas Ad5(GL) was blocked. In contrast, crossblocking by NAbs induced by different viruses affected gene delivery to normal human lung explants, suggesting the importance of non-fiber-knob-mediated infection mechanisms. We conclude that changing the adenovirus fiber knob is sufficient to allow a relative degree of escape from preexisting NAb. If confirmed in trials, this approach might improve the efficacy of re-administration of adenoviral gene therapy to humans.     

Neurovascular compression (conflict)]

Since Dandy first reported vascular compression of the trigeminal nerve, the concept of neurovascular compression syndrome for trigeminal neuralgia and hemifacial spasm (HFS) has been accepted, and neurovascular decompression has been performed for this condition. The further investigations indicated that some other clinical syndromes such as glossopharyngeal neuralgia, disabling positional vertigo, tinnitus, geniculate neuarlgia, spasmodic torticolis, essential hypertension, cyclic oculomotor spasm with paresis and superior oblique myokymia also may be initiated by vascular compression of the glossopharyngeal, cochleovestibular, intermediate, accessory, oculomotor and trochlear nerves or the ventrolateral medulla oblongata. In this study several hypotheses regarding the development of cranial nerves vascular compression syndromes are presented. It is alsoemphasized the value of high-resolution magnetic resonance tomographic angiography for visualization of vascular compression. The most frequent clinical syndromes caused by vascular compressionof the cranial nerves are discussed regarding the pathogenesis, symptomes and therapy. We present our series of 124 patients with preoperative evidently positive finding of vascular compression to the trigeminal nerve (MRI). Microvascular decompression (MVD) was performed in all of them. Initial postoperative result was excellent in 110/124 (89%) patients,while in 11/124 (9%) patients the pain relief was satisfactory. In the remaining three patients MVD failed. Recurrence of pain after two years reached 19%. Complications were related to diplopia associated with transient fourth nerve dysfunction in 5 (4%) patients, facial motor dysfunction in 4 (3%) patients, transient facial hypesthesia in 27 (22%) patients and partially hearing loss in 4 (3%) patients. Cerebellar hemorrhagic infarction occurred in 1 (0.8%) patient and cerebrospinal fluid leaks appeared in two (1.6%) cases. There was no lethal outcome.     

Morphologic analysis of the coexisting anomalies of the arteries of the cerebral base and aneurysms: clinical study

During operations of the aneurysms showing anatomical details is the means that leads to the aim, and it is not only a purpose in itself. Data on details that the surgeons come across during their work and which sometimes represent difficulties during interpretations of angiographic findings and planning operations, as well as the intraoperative orientations and identifications of the elements . Frequency of occurrence of such anatomical details and anomalies may be completely different from the one that autopsy series show. Knowledge of this makes the work of surgeons easier and gives a necessary feeling of confidence during operations. Thus, we decided to conduct a clinical, morphological study based on angiographic and surgical analyses of the explored segments of the Wilson circle. The study included 344 patients from the Institute for Neurosurgery, during the period of 2 years; the patients had complete angiographic diagnosing and operative exploration. Our findings confirm differences in localization of aneurysms according to sex. Aneurysms on the front communicant complex are to a great extent associated with anomalies of the front part of the Wilson circle.     

Purine analogs sensitize the multidrug resistant cell line (NCI-H460/R) to doxorubicin and stimulate the cell growth inhibitory effect of verapamil

The resistant cell line NCI-H460/R and its counterpart NCI-H460 were used to investigate the ability of purine analogs to overcome multidrug resistance (MDR) that seriously limit the efficacy of lung cancer regimens with chemotherapeutic agents. Two purine analogs, sulfinosine (SF) and 8-Cl-cAMP, exerted dose-dependent effects on cell growth in both parental and resistant cell lines. They significantly decreased mdr1 expression in NCI-H460/R cells. Low concentrations (1 μM) of SF and 8-Cl-cAMP in combination with doxorubicin (DOX) exerted synergistic growth inhibition in both cell lines. Pretreatment with SF and 8-Cl-cAMP improved the sensitivity to DOX more than verapamil (VER), the standard modulator of MDR. The increased accumulation of DOX observed after the treatment with SF and 8-Cl-cAMP was consistent with the results obtained with VER. VER stimulated the effect of 8-Cl-cAMP on DOX cytotoxicity and mdr1 expression. Combinations of either SF or 8-Cl-cAMP with VER at clinically acceptable concentrations exhibited synergistic effects on cell growth inhibition in the resistant cell line. SF and 8-Cl-cAMP modulated MDR in NCI-H460/R cells, especially when applied before DOX administration. This feature, together with their ability to reverse MDR, renders the purine analogs (in combination with VER) as potential candidates for improving the clinical activity of existing lung cancer therapeutics.