Browsing by Subject "TRANSPORT"

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  • Du, Wei; Dada, Lubna; Zhao, Jian; Chen, Xueshun; Dällenbach, Kaspar; Xie, Conghui; Wang, Weigang; He, Yao; Cai, Jing; Yao, Lei; Zhang, Yingjie; Wang, Qingqing; Xu, Weiqi; Wang, Yuying; Tang, Guiqian; Cheng, Xueling; Kokkonen, Tom V.; Zhou, Wei; Yan, Chao; Chu, Biwu; Zha, Qiaozhi; Hakala, Simo; Kurppa, Mona; Jarvi, Leena; Liu, Yongchun; Li, Zhanqing; Ge, Maofa; Fu, Pingqing; Nie, Wei; Bianchi, Federico; Petäjä, Tuukka; Paasonen, Pauli; Wang, Zifa; Worsnop, Douglas R.; Kerminen, Veli-Matti; Kulmala, Markku; Sun, Yele (2021)
    The role of new particle formation (NPF) events and their contribution to haze formation through subsequent growth in polluted megacities is still controversial. To improve the understanding of the sources, meteorological conditions, and chemistry behind air pollution, we performed simultaneous measurements of aerosol composition and particle number size distributions at ground level and at 260 m in central Beijing, China, during a total of 4 months in 2015-2017. Our measurements show a pronounced decoupling of gas-to-particle conversion between the two heights, leading to different haze processes in terms of particle size distributions and chemical compositions. The development of haze was initiated by the growth of freshly formed particles at both heights, whereas the more severe haze at ground level was connected directly to local primary particles and gaseous precursors leading to higher particle growth rates. The particle growth creates a feedback loop, in which a further development of haze increases the atmospheric stability, which in turn strengthens the persisting apparent decoupling between the two heights and increases the severity of haze at ground level. Moreover, we complemented our field observations with model analyses, which suggest that the growth of NPF-originated particles accounted up to similar to 60% of the accumulation mode particles in the Beijing-Tianjin-Hebei area during haze conditions. The results suggest that a reduction in anthropogenic gaseous precursors, suppressing particle growth, is a critical step for alleviating haze although the number concentration of freshly formed particles (3-40 nm) via NPF does not reduce after emission controls.
  • Flatt, Justin W.; Butcher, Sarah J. (2019)
    Viruses are obligatory parasites that take advantage of intracellular niches to replicate. During infection, their genomes are carried in capsids across the membranes of host cells to sites of virion production by exploiting cellular behaviour and resources to guide and achieve all aspects of delivery and the downstream virus manufacturing process. Successful entry hinges on execution of a precisely tuned viral uncoating program where incoming capsids disassemble in consecutive steps to ensure that genomes are released at the right time, and in the right place for replication to occur. Each step of disassembly is cell-assisted, involving individual pathways that transmit signals to regulate discrete functions, but at the same time, these signalling pathways are organized into larger networks, which communicate back and forth in complex ways in response to the presence of virus. In this review, we consider the elegant strategy by which adenoviruses (AdVs) target and navigate cellular networks to initiate the production of progeny virions. There are many remarkable aspects about the AdV entry program; for example, the virus gains targeted control of a large well-defined local network neighbourhood by coupling several interacting processes (including endocytosis, autophagy and microtubule trafficking) around a collective reference state centred on the interactional topology and multifunctional nature of protein VI. Understanding the network targeting activity of protein VI, as well as other built-in mechanisms that allow AdV particles to be efficient at navigating the subsystems of the cell, can be used to improve viral vectors, but also has potential to be incorporated for use in entirely novel delivery systems.
  • Meneses-Salas, Elsa; García-Melero, Ana; Kanerva, Kristiina; Blanco-Muñoz, Patricia; Morales-Paytuvi, Frederic; Bonjoch, Júlia; Heeren, Joerg; Lu, Albert; Pol, Albert; Tebar, Francesc; Ikonen, Elina; Grewal, Thomas; Enrich, Carlos; Rentero, Carles (2020)
    Cholesterol accumulation in late endosomes is a prevailing phenotype of Niemann-Pick type C1 (NPC1) mutant cells. Likewise, annexin A6 (AnxA6) overexpression induces a phenotype reminiscent of NPC1 mutant cells. Here, we demonstrate that this cellular cholesterol imbalance is due to AnxA6 promoting Rab7 inactivation via TBC1D15, a Rab7-GAP. In NPC1 mutant cells, AnxA6 depletion and eventual Rab7 activation was associated with peripheral distribution and increased mobility of late endosomes. This was accompanied by an enhanced lipid accumulation in lipid droplets in an acyl-CoA:cholesterol acyltransferase (ACAT)-dependent manner. Moreover, in AnxA6-deficient NPC1 mutant cells, Rab7-mediated rescue of late endosome-cholesterol export required the StAR-related lipid transfer domain-3 (StARD3) protein. Electron microscopy revealed a significant increase of membrane contact sites (MCS) between late endosomes and ER in NPC1 mutant cells lacking AnxA6, suggesting late endosome-cholesterol transfer to the ER via Rab7 and StARD3-dependent MCS formation. This study identifies AnxA6 as a novel gatekeeper that controls cellular distribution of late endosome-cholesterol via regulation of a Rab7-GAP and MCS formation.
  • Chauvigné, Aurélien; Aliaga, Diego; Sellegri, Karine; Montoux, Nadège; Krejci, Radovan; Močnik, Griša; Moreno, Isabel; Müller, Thomas; Pandolfi, Marco; Velarde, Fernando; Weinhold, Kay; Ginot, Patrick; Wiedensohler, Alfred; Andrade, Marcos; Laj, Paolo (2019)
    This study documents and analyses a 4-year continuous record of aerosol optical properties measured at the Global Atmosphere Watch (GAW) station of Chacaltaya (CHC; 5240 m a.s.l.), in Bolivia. Records of particle light scattering and particle light absorption coefficients are used to investigate how the high Andean Cordillera is affected by both long-range transport and by the fast-growing agglomeration of La Paz-El Alto, located approximately 20 km away and 1.5 km below the sampling site. The extended multiyear record allows us to study the properties of aerosol particles for different air mass types, during wet and dry seasons, also covering periods when the site was affected by biomass burning in the Bolivian lowlands and the Amazon Basin. The absorption, scattering, and extinction coefficients (median annual values of 0.74, 12.14, and 12.96 Mm(-1) respectively) show a clear seasonal variation with low values during the wet season (0.57, 7.94, and 8.68 Mm(-1) respectively) and higher values during the dry season (0.80, 11.23, and 14.51 Mm(-1) respectively). The record is driven by variability at both seasonal and diurnal scales. At a diurnal scale, all records of intensive and extensive aerosol properties show a pronounced variation (daytime maximum, night-time minimum), as a result of the dynamic and convective effects. The particle light absorption, scattering, and extinction coefficients are on average 1.94, 1.49, and 1.55 times higher respectively in the turbulent thermally driven conditions than the more stable conditions, due to more efficient transport from the boundary layer. Retrieved intensive optical properties are significantly different from one season to the other, reflecting the changing aerosol emission sources of aerosol at a larger scale. Using the wavelength dependence of aerosol particle optical properties, we discriminated between contributions from natural (mainly mineral dust) and anthropogenic (mainly biomass burning and urban transport or industries) emissions according to seasons and local circulation. The main sources influencing measurements at CHC are from the urban area of La Paz-El Alto in the Altiplano and from regional biomass burning in the Amazon Basin. Results show a 28 % to 80 % increase in the extinction coefficients during the biomass burning season with respect to the dry season, which is observed in both tropospheric dynamic conditions. From this analysis, long-term observations at CHC provide the first direct evidence of the impact of biomass burning emissions of the Amazon Basin and urban emissions from the La Paz area on atmospheric optical properties at a remote site all the way to the free troposphere.
  • Adam, J.; Brucken, E. J.; Chang, B.; Hilden, T. E.; Kim, D. J.; Kral, J.; Mieskolainen, M. M.; Orava, R.; Rak, J.; Räsänen, S. S.; Snellman, T. W.; Trzaska, W. H.; The ALICE collaboration (2015)
    The nuclear modification factor, R-AA, of the prompt charmed mesons D-0, D+ and D*+, and their antiparticles, was measured with the ALICE detector in Pb-Pb collisions at a centre-of-mass energy root s(NN) = 2 : 76 TeV in two transverse momentum intervals, 5 <p(T) <8 GeV/c and 8 <p(T) <16 GeV/c, and in six collision centrality classes. The R-AA shows a maximum suppression of a factor of 5{6 in the 10% most central collisions. The suppression and its centrality dependence are compatible within uncertainties with those of charged pions. A comparison with the R-AA of non-prompt J/psi from B meson decays, measured by the CMS Collaboration, hints at a larger suppression of D mesons in the most central collisions.
  • Jiang, Jianhui; Aksoyoglu, Sebnem; Ciarelli, Giancarlo; Baltensperger, Urs; Prévôt, André S.H. (2020)
    Air pollution is among the top threats to human health and ecosystems despite the substantial decrease in anthropogenic emissions. Meanwhile, the role of ship emissions on air quality is becoming increasingly important with the growing maritime transport and less strict regulations. In this study, we modeled the air quality in Europe between 1990 and 2030 with ten-year intervals, using the regional air quality model CAMx version 6.50, to investigate the changes in the past (1990-2010) as well as the effects of different land and ship emission scenarios in the future (2020,2030). The modeled mean ozone levels decreased slightly during the first decade but then started increasing again especially in polluted areas. Results from the future scenarios suggest that by 2030 the peak ozone would decrease, leading to a decrease in the days exceeding the maximum daily 8-h average ozone (MDA8) limit values (60 ppb) by 51% in southern Europe relative to 1990. The model results show a decrease of 56% (6.3 mu g m(-3)) in PM2.5 concentrations from 1990 to 2030 under current legislation, mostly due to a large drop in sulfate (representing up to 44% of the total PM2.5 decrease during 1990-2000) while nitrate concentrations were predicted to go down with an increasing rate (10% of total PM2.5 decrease during 1990-2000 while 36% during 2020-2030). The ship emissions if reduced according to the maximum technically feasible reduction (MTFR) scenario were predicted to contribute up to 19% of the decrease in the PM2.5 concentrations over land between 2010 and 2030. Ship emission reductions according to the MTFR scenario would lead to a decrease in the days with MDA8 exceeding EU limits by 24-28% (10-14 days) around the coastal regions. The results obtained in our study show the increasing importance of ship emission reductions, after a relatively large decrease in land emissions was achieved in Europe. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
  • Siljamaki, Elina; Rintanen, Nina; Kirsi, Maija; Upla, Paula; Wang, Wei; Karjalainen, Mikko; Ikonen, Elina; Marjomaki, Varpu (2013)
  • Vainio, Annukka; Varho, Vilja; Tapio, Petri; Pulkka, Anna; Paloniemi, Riikka (2019)
    Achieving a sustainable energy transition is crucial for mitigating climate change. Citizens' acceptance of the transition is important for it to succeed. We explored citizens' images of the future energy forms and energy system in Finland, and the drivers of a sustainable energy transition. The data gathered with an online questionnaire targeting an adult population 17–75 years of age (N = 1012) were analysed with exploratory factor analysis and multiple linear regression. Four dimensions of future energy forms were identified: next-generation renewables, fossil energy, bioenergy, and established renewable vs. nuclear energy. Four dimensions of the future energy system were also identified: renewing the energy market, domestic power, small-scale producers, and consumer awareness. Five transition drivers were likewise identified: mainstreaming renewable energy, international actors, individual actions, changing values and economy, and emancipatory change. Mainstreaming renewable energy emerged as the key driver of transition, followed by individual actions. Generally, the sustainable energy transition was strongly supported by citizens' images, but different socio-economic groups preferred somewhat different images. Thus, the diversity of consumers' and citizens’ roles in the transition needs to be acknowledged and encouraged in legitimate national energy policies.
  • Nikandrova, Anna; Tabakova, Ksenia; Manninen, Antti J.; Väänänen, Riikka; Petäjä, Tuukka; Kulmala, Markku; Kerminen, Veli-Matti; O'Connor, Ewan (2018)
    Understanding the distribution of aerosol layers is important for determining long-range transport and aerosol radiative forcing. In this study we combine airborne in situ measurements of aerosol with data obtained by a ground-based high spectral resolution lidar (HSRL) and radiosonde profiles to investigate the temporal and vertical variability of aerosol properties in the lower troposphere. The HSRL was deployed in Hyytiala, southern Finland, from January to September 2014 as a part of the U.S. DOE ARM (Atmospheric Radiation Measurement) mobile facility during the BAECC (Biogenic Aerosols - Effects on Cloud and Climate) Campaign. Two flight campaigns took place in April and August 2014 with instruments measuring the aerosol size distribution from 10 nm to 5 mu m at altitudes up to 3800 m. Two case studies with several aerosol layers present were selected from the flight campaigns for further investigation: one clear-sky and one partly cloudy case. During the clear-sky case, turbulent mixing ensured small temporal and spatial variability in the measured aerosol size distribution in the boundary layer, whereas mixing was not as homogeneous in the boundary layer during the partly cloudy case. The elevated layers exhibited larger temporal and spatial variability in aerosol size distribution, indicating a lack of mixing. New particle formation was observed in the boundary layer during the clear-sky case, and nucleation mode particles were also seen in the elevated layers that were not mixing with the boundary layer. Interpreting local measurements of elevated layers in terms of long-range transport can be achieved using back trajectories from Lagrangian models, but care should be taken in selecting appropriate arrival heights, since the modelled and observed layer heights did not always coincide. We conclude that higher confidence in attributing elevated aerosol layers to their air mass origin is attained when back trajectories are combined with lidar and radiosonde profiles.
  • Voutilainen, Mikko; Kekäläinen, Pekka; Poteri, Antti; Siitari-Kauppi, Marja; Helariutta, Kerttuli; Andersson, Peter; Nilsson, Kersti; Byegård, Johan; Skålberg, Mats; Yli-Kaila, Maarit; Koskinen, Lasse (2019)
    In some countries the spent nuclear fuel produced by nuclear power plants will be deposited in crystalline granitic rock formations. In Finland, a repository for the spent nuclear fuel is being built at Olkiluoto. The safety assessment of the repository requires a careful determination of the transport properties of the bedrock. The porosity of the bedrock and the effective diffusion coefficients and distribution coefficients of different radio-nuclides for the bedrock are used as the main parameters in the safety assessment calculations. It has been questioned whether the parameters determined using laboratory experiments can be used to estimate the parameters in the in situ conditions. In this study, laboratory and in situ water phase diffusion experiments (WPDEs) were performed to resolve the issue. In the experiments, the transport of tritiated water (HTO), Cl-36, and Na-22 was studied using similar experimental setups. Mathematical models were constructed and solved to determine the transport parameters from the measured breakthrough curves. On average, the in situ WPDEs resulted in 20 (+/- 6)% smaller porosities and 32 (+/- 10)% smaller effective diffusion coefficients for HTO and Cl-36 than the laboratory WPDEs. It was also found that in veined gneiss, the most dominant rock type of the Olkiluoto bedrock, anion exclusion reduced the retention parameters of Cl-36 compared with those of HTO. Furthermore, the distribution coefficient of Na-22 for veined gneiss was about one order of magnitude smaller in the in situ conditions than in previous laboratory batch sorption experiments. The effects of the results on the safety assessment were evaluated and discussed.
  • Lucke, Bernhard; Sandler, Amir; Vanselow, Kim André; Bruins, Hendrik J.; Abu-Jaber, Nizar; Baeumler, Rupert; Porat, Naomi; Kouki, Paula (2019)
    Archaeological structures are often filled with sediments and may serve as effective dust traps. The physical parameters and chemical composition of archaeological soils in hilltop ruins, ancient runoff-collecting terraces, and cleanout spoils of cisterns were determined in the Petra region in southern Jordan and the Northern Negev in Israel. Different types of ruins are characterized by certain soil structures, but could not be distinguished with regard to substrate composition. This reflects a predominance of aeolian processes for primary sedimentation, while fluvial processes seem to only re-distribute aeolian material. In the Petra region, the physical and chemical properties of all archaeological soils show a significant local contribution from associated weathered rocks. Compared to modern settled dust, archaeological soils in Southern Jordan are enriched with various major and trace elements associated with clays and oxide coatings of fine silt particles. This seems connected with preferential fixation of silt and clay by surface crusts, and a role of moisture in sedimentation processes as calcareous silt was found to be deposited in greater amounts when associated with precipitation. In contrast, the contribution of rocks is negligible in the Negev due to greater rock hardness and abundant biological crusts that seal surfaces. Archaeological soils in the Negev are chemically similar to current settled dust, which consists of complex mixtures of local and remote sources, including significant portions of recycled material from paleosols. Archaeological soils are archives of Holocene dust sources and aeolian sedimentation processes, with accretion rates exceeding those of Pleistocene hilltop loess in the Negev. Comparison with Pleistocene paleosols suggests that dust sources did not change significantly, but disappearance of snow could have reduced dust accumulation during the Holocene.
  • Enkavi, Giray; Mikkolainen, Heikki; Gungor, Burcin; Ikonen, Elina; Vattulainen, Ilpo (2017)
    Niemann-Pick Protein C2 (NPC2) is a small soluble protein critical for cholesterol transport within and from the lysosome and the late endosome. Intriguingly, NPC2-mediated cholesterol transport has been shown to be modulated by lipids, yet the molecular mechanism of NPC2-membrane interactions has remained elusive. Here, based on an extensive set of atomistic simulations and free energy calculations, we clarify the mechanism and energetics of NPC2-membrane binding and characterize the roles of physiologically relevant key lipids associated with the binding process. Our results capture in atomistic detail two competitively favorable membrane binding orientations of NPC2 with a low interconversion barrier. The first binding mode (Prone) places the cholesterol binding pocket in direct contact with the membrane and is characterized by membrane insertion of a loop (V59-M60-G61-I62-P63-V64P65). This mode is associated with cholesterol uptake and release. On the other hand, the second mode (Supine) places the cholesterol binding pocket away from the membrane surface, but has overall higher membrane binding affinity. We determined that bis(monoacylglycero) phosphate (BMP) is specifically required for strong membrane binding in Prone mode, and that it cannot be substituted by other anionic lipids. Meanwhile, sphingomyelin counteracts BMP by hindering Prone mode without affecting Supine mode. Our results provide concrete evidence that lipids modulate NPC2-mediated cholesterol transport either by favoring or disfavoring Prone mode and that they impose this by modulating the accessibility of BMP for interacting with NPC2. Overall, we provide a mechanism by which NPC2-mediated cholesterol transport is controlled by the membrane composition and how NPC2-lipid interactions can regulate the transport rate.
  • Im, Ulas; Christensen, Jesper H.; Nielsen, Ole-Kenneth; Sand, Maria; Makkonen, Risto; Geels, Camilla; Anderson, Camilla; Kukkonen, Jaakko; Lopez-Aparicio, Susana; Brandt, Jørgen (2019)
    This modeling study presents the sectoral contributions of anthropogenic emissions in the four Nordic countries (Denmark, Finland, Norway and Sweden) on air pollution levels and the associated health impacts and costs over the Nordic and the Arctic regions for the year 2015. The Danish Eulerian Hemispheric Model (DEHM) has been used on a 50 km resolution over Europe in tagged mode in order to calculate the response of a 30 % reduction of each emission sector in each Nordic country individually. The emission sectors considered in the study were energy production, non-industrial/commercial heating, industry, traffic, off-road mobile sources and waste management/agriculture. In total, 28 simulations were carried out. Following the air pollution modeling, the Economic Valuation of Air Pollution (EVA) model has been used to calculate the associated premature mortality and their costs. Results showed that more than 80 % of the PM2.5 concentration was attributed to transport from outside these four countries, implying an effort outside the Nordic region in order to decrease the pollutant levels over the area. The leading emission sector in each country was found to be non-industrial combustion (contributing by more than 60 % to the total PM2.5 mass coming from the country itself), except for Sweden, where industry contributed to PM2.5 with a comparable amount to non-industrial combustion. In addition to non-industrial combustion, the next most important source categories were industry, agriculture and traffic. The main chemical constituent of PM2.5 concentrations that comes from the country itself is calculated to be organic carbon in all countries, which suggested that nonindustrial wood burning was the dominant national source of pollution in the Nordic countries. We have estimated the total number of premature mortality cases due to air pollution to be around 4000 in Denmark and Sweden and around 2000 in Finland and Norway. These premature mortality cases led to a total cost of EUR 7 billion in the selected Nordic countries. The assessment of the related premature mortality and associated cost estimates suggested that non-industrial combustion, together with industry and traffic, will be the main sectors to be targeted in emission mitigation strategies in the future.
  • Halonen, Jaana; Pulakka, Anna; Pentti, Jaana; Kallio, Minna; Koskela, Sofia; Kivimäki, Mika; Kawachi, Ichiro; Vahtera, Jussi; Stenholm, Sari (2020)
    Objective Neighbourhood characteristics may affect the level of physical activity (PA) of the residents. Few studies have examined the combined effects of distinctive neighbourhood characteristics on PA using objective data or differentiated between activity during working or non-working days. We examined the associations of socioeconomic disadvantage and greenness with accelerometer-measured leisure-time PA during working and non-working days. Design Cross-sectional study. Setting Finnish Retirement and Aging (FIREA) study. Participants 708 workers (604 women, mean age 62.4 ranging from 58 to 64 years,) participating in the FIREA study who provided PA measurement data for at least 1 working and non-working day. Primary and secondary outcomes PA was measured with wrist-worn accelerometer on average of 4 working and 2 non-working days. Outcomes were total PA, light PA (LPA) and moderate-to-vigorous PA (MVPA). These measurements were linked to data on neighbourhood socioeconomic disadvantage and greenness within the home neighbourhood (750x750 m). Generalised linear models were adjusted for possible confounders. Results On non-working days, higher neighbourhood disadvantage associated with lower levels of total PA (p value=0.07) and higher level of neighbourhood greenness associated with higher level of total PA (p value=0.04). Neighbourhood disadvantage and greenness had an interaction (p value=0.02); in areas of low disadvantage higher greenness did not associate with the level of total PA. However, in areas of high disadvantage, 2 SD higher greenness associated with 46 min/day (95% CI 8.4 to 85) higher total PA. Slightly stronger interaction was observed for LPA (p=0.03) than for the MVPA (p=0.09). During working days, there were no associations between neighbourhood characteristics and leisure-time total PA. Conclusions Of the disadvantaged neighbourhoods, those characterised by high levels of greenness seem to associate with higher levels of leisure-time PA during non-working days. These findings suggest that efforts to add greenness to socioeconomically disadvantaged neighbourhoods might reduce inequalities in PA.
  • Nieminen, Heikki J.; Ylitalo, Tuomo; Suuronen, Jussi-Petteri; Rahunen, Krista; Salmi, Ari; Saarakkala, Simo; Serimaa, Ritva; Haeggstrom, Edward (2015)
    There is no cure for osteoarthritis. Current drug delivery relies on systemic delivery or injections into the joint. Because articular cartilage (AC) degeneration can be local and drug exposure outside the lesion can cause adverse effects, localized drug delivery could permit new drug treatment strategies. We investigated whether intense megahertz ultrasound (frequency: 1.138 MHz, peak positive pressure: 2.7 MPa, I-spta: 5 W/cm(2), beam width: 5.7 mm at -6 dB, duty cycle: 5%, pulse repetition frequency: 285 Hz, mechanical index: 1.1) can deliver agents into AC without damaging it. Using ultrasound, we delivered a drug surrogate down to a depth corresponding to 53% depth of the AC thickness without causing histologically detectable damage to the AC. This may be important because early osteoarthritis typically exhibits histopathologic changes in the superficial AC. In conclusion, we identify intense megahertz ultrasound as a technique that potentially enables localized non-destructive delivery of osteoarthritis drugs or drug carriers into articular cartilage. (E-mail: heikki.nieminen@helsinki.fi) (C) 2015 World Federation for Ultrasound in Medicine & Biology.
  • Lilius, Tuomas O.; Blomqvist, Kim; Hauglund, Natalie; Liu, Guojun; Stæger, Frederik Filip; Bærentzen, Simone; Du, Ting; Ahlström, Fredrik; Backman, Janne T.; Kalso, Eija; Rauhala, Pekka V.; Nedergaard, Maiken (2019)
    Drug delivery to the central nervous system remains a major problem due to biological barriers. The blood-brainbarrier can be bypassed by administering drugs intrathecally directly to the cerebrospinal fluid (CSF). The glymphatic system, a network of perivascular spaces promoting fluid exchange between CSF and interstitial space, could be utilized to enhance convective drug delivery from the CSF to the parenchyma. Glymphatic flow is highest during sleep and anesthesia regimens that induce a slow-wave sleep-like state. Here, using mass spectrometry and fluorescent imaging techniques, we show that the clinically used alpha(2)-adrenergic agonist dexme-detomidine that enhances EEG slow-wave activity, increases brain and spinal cord drug exposure of intrathecally administered drugs in mice and rats. Using oxycodone, naloxone, and an IgG-sized antibody as relevant model drugs we demonstrate that modulation of glymphatic flow has a distinct impact on the distribution of intrathecally administered therapeutics. These findings can be exploited in the clinic to improve the efficacy and safety of intrathecally administered therapeutics.
  • Malinen, Melina M.; Kanninen, Liisa K.; Corlu, Anne; Isoniemi, Helena M.; Lou, Yan-Ru; Yliperttula, Marjo L.; Urtti, Arto O. (2014)
  • Yeung, J.; Matsuyama, T.; Bray, J.; Reynolds, J.; Skrifvars, M. B. (2019)
    Aim: To perform a systematic review to answer 'In adults with attempted resuscitation after non-traumatic cardiac arrest does care at a specialised cardiac arrest centre (CAC) compared to care in a healthcare facility not designated as a specialised cardiac arrest centre improve patient outcomes?' Methods: The PRISMA guidelines were followed. We searched bibliographic databases (Embase, MEDLINE and the Cochrane Library (CENTRAL)) from inception to 1st August 2018. Randomised controlled trials (RCTs) and non-randomised studies were eligible for inclusion. Two reviewers independently scrutinized studies for relevance, extracted data and assessed quality of studies. Risk of bias of studies and quality of evidence were assessed using ROBINS-I tool and GRADEpro respectively. Primary outcomes were survival to 30 days with favourable neurological outcomes and survival to hospital discharge with favourable neurological outcomes. Secondary outcomes were survival to 30 days, survival to hospital discharge and return of spontaneous circulation (ROSC) post-hospital arrival for patients with ongoing resuscitation. This systematic review was registered in PROSPERO (CRD 42018093369) Results: We included data from 17 observational studies on out-of-hospital cardiac arrest (OHCA) patients in meta-analyses. Overall, the certainty of evidence was very low. Pooling data from only adjusted analyses, care at CAC was not associated with increased likelihood of survival to 30 days with favourable neurological outcome (OR 2.92, 95% CI 0.68-12.48) and survival to 30 days (OR 2.14, 95% CI 0.73-6.29) compared to care at other hospitals. Whereas patients cared for at CACs had improved survival to hospital discharge with favourable neurological outcomes (OR 2.22, 95% CI 1.74-2.84) and survival to hospital discharge (OR 1.85, 95% CI 1.46-2.34). Conclusions: Very low certainty of evidence suggests that post-cardiac arrest care at CACs is associated with improved outcomes at hospital discharge. There remains a need for high quality data to fully elucidate the impact of CACs.
  • Muuri, Eveliina; Sorokina, Tatiana; Donnard, Jerome; Billon, Sophie; Helariutta, Kerttuli; Koskinen, Lasse; Martin, Andrew; Siitari-Kauppi, Marja (2019)
    The spatial distribution of barium activity in granitic rocks was measured with two autoradiography techniques; digital autoradiography using phosphor imaging plate technique (Fuji 5100) and filmless electronic autoradiography (i.e. The BeaQuant (TM)), which is based on a gas detector incorporated in a micromesh Parallel Ionization Multiplier (PIM). Rock cubes taken from a diffusion experiment that were in contact with Ba-133 tracer were measured to determine diffusion profiles. In addition, the spatial distribution of Ba-133 in the samples was determined. Polymethyl methacrylate standards for Ba-133 were developed to determine the counting efficiency for electronic autoradiography. Good visual correlation between the two autoradiography methods were obtained in this study. The results of the experiments presented here can be utilized in future studies on the diffusion behavior of barium in granitic rocks.