465 research outputs found

    Tapahtuma-alan toimialamääritys ja yhteydet kaupunkikehittämiseen

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    Tapahtuma-alan liikevaihto Suomessa vuonna 2019 oli 2,35 miljardia euroa. Ala työllistää vakituisesti noin 20 000 henkilöä ja tilapäisesti 120 000–175 000. Tapahtuma-ala on 2000-luvun ajan kasvussa ollut työvoimaintensiivinen ala, joka kärsi vuosina 2020–2022 suuresti koronapandemian vuoksi asetetuista kokoontumisrajoituksista. Pandemia nosti esille kolme alan kehityksen kannalta keskeistä ongelmaa: tapahtuma-alaa ei ole tunnistettu elinkeinona, alaa ei ole kokonaisuutena määritelty ja alan yrityksiä ei tunnisteta tilastoinnissa. Tällöin alan yhteiskunnallista vaikuttavuutta ei myöskään ole voitu systemaattisesti tunnistaa. Tämä selvitys käsittelee näitä teemoja. Tapahtuma-alan kehitys ammattimaiseksi toimialaksi alkaa 1990-luvulta. Alan toiminta perustuu pienten ja keskisuurten yritysten muodostamaan verkostomaiseen ekosysteemiin. Alan toimintarakenteet, joissa korostuu yksinyrittäjien merkittävä määrä, epätyypilliset työsuhteet ja sesonkiluonteisuus ovat muovautuneet tarpeesta sopeutua muuttuvissa olosuhteissa. Yhteiskunnan toimijoista kaupungit ovat nopeimmin tunnistaneet tapahtuma-alan merkityksen. Kaupunkien välillä kuitenkin on eroja siinä, miten ne tunnistavat ja mittaavat tapahtumien vaikutuksia talouteen, imagoon ja identiteettiin sekä hyvinvoinnin ja yhteisöllisyyden kokemuksiin. Kaupungit myös hyödyntävät eritasoisesti tapahtumia näiden tavoitteiden saavuttamiseen. Tulevaisuuden kehityskohteita ovat alan vaikuttavuuden tunnistaminen, kasvun esteiden poistaminen sekä alan tilastoinnin ja tiedonkeruun parantaminen

    HIV-1 non-macrophage-tropic R5 envelope glycoproteins are not more tropic for entry into primary CD4+ T-cells than envelopes highly adapted for macrophages

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    BACKGROUND: Non-mac-tropic HIV-1 R5 viruses are predominantly transmitted and persist in immune tissue even in AIDS patients who carry highly mac-tropic variants in the brain. Non-mac-tropic R5 envelopes (Envs) require high CD4 levels for infection contrasting with highly mac-tropic Envs, which interact more efficiently with CD4 and mediate infection of macrophages that express low CD4. Non-mac-tropic R5 Envs predominantly target T-cells during transmission and in immune tissue where they must outcompete mac-tropic variants. Here, we investigated whether Env+ pseudoviruses bearing transmitted/founder (T/F), early and late disease non-mac-tropic R5 envelopes mediated more efficient infection of CD4+ T-cells compared to those with highly mac-tropic Envs. RESULTS: Highly mac-tropic Envs mediated highest infectivity for primary T-cells, Jurkat/CCR5 cells, myeloid dendritic cells, macrophages, and HeLa TZM-bl cells, although this was most dramatic on macrophages. Infection of primary T-cells mediated by all Envs was low. However, infection of T-cells was greatly enhanced by increasing virus attachment with DEAE dextran and spinoculation, which enhanced the three Env+ virus groups to similar extents. Dendritic cell capture of viruses and trans-infection also greatly enhanced infection of primary T-cells. In trans-infection assays, non-mac-tropic R5 Envs were preferentially enhanced and those from late disease mediated levels of T-cell infection that were equivalent to those mediated by mac-tropic Envs. CONCLUSIONS: Our results demonstrate that T/F, early or late disease non-mac-tropic R5 Envs do not preferentially mediate infection of primary CD4+ T-cells compared to highly mac-tropic Envs from brain tissue. We conclude that non-macrophage-tropism of HIV-1 R5 Envs in vitro is determined predominantly by a reduced capacity to target myeloid cells via low CD4 rather than a specific adaptation for T-cells entry that precludes macrophage infection

    The conformational state of hERG1 channels determines integrin association, downstream signaling, and cancer progression

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    Ion channels regulate cell proliferation, differentiation, and migration in normal and neoplastic cells through cell-cell and cell-extracellular matrix (ECM) transmembrane receptors called integrins. K+ flux through the human ether-\ue0-gogo- related gene 1 (hERG1) channel shapes action potential firing in excitable cells such as cardiomyocytes. Its abundance is often aberrantly high in tumors, where it modulates integrin-mediated signaling. We found that hERG1 interacted with the \u3b21 integrin subunit at the plasma membrane of human cancer cells. This interaction was not detected in cardiomyocytes because of the presence of the hERG1 auxiliary subunit KCNE1 (potassium voltage-gated channel subfamily E regulatory subunit 1), which blocked the \u3b21 integrin-hERG1 interaction. Although open hERG1 channels did not interact as strongly with \u3b21 integrins as did closed channels, current flow through hERG1 channelswas necessary to activate the integrin-dependent phosphorylation of Tyr397 in focal adhesion kinase (FAK) in both normal and cancer cells. In immunodeficient mice, proliferation was inhibited in breast cancer cells expressing forms of hERG1 with impaired K+ flow, whereas metastasis of breast cancer cells was reduced when the hERG1/\u3b21 integrin interaction was disrupted. We conclude that the interaction of \u3b21 integrins with hERG1 channels in cancer cells stimulated distinct signaling pathways that depended on the conformational state of hERG1 and affected different aspects of tumor progression

    Assessing the optimized precision of the aircraft mass balance method for measurement of urban greenhouse gas emission rates through averaging

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    To effectively address climate change, aggressive mitigation policies need to be implemented to reduce greenhouse gas emissions. Anthropogenic carbon emissions are mostly generated from urban environments, where human activities are spatially concentrated. Improvements in uncertainty determinations and precision of measurement techniques are critical to permit accurate and precise tracking of emissions changes relative to the reduction targets. As part of the INFLUX project, we quantified carbon dioxide (CO2), carbon monoxide (CO) and methane (CH4) emission rates for the city of Indianapolis by averaging results from nine aircraft-based mass balance experiments performed in November-December 2014. Our goal was to assess the achievable precision of the aircraft-based mass balance method through averaging, assuming constant CO2, CH4 and CO emissions during a three-week field campaign in late fall. The averaging method leads to an emission rate of 14,600 mol/s for CO2, assumed to be largely fossil-derived for this period of the year, and 108 mol/s for CO. The relative standard error of the mean is 17% and 16%, for CO2 and CO, respectively, at the 95% confidence level (CL), i.e. a more than 2-fold improvement from the previous estimate of ~40% for single-flight measurements for Indianapolis. For CH4, the averaged emission rate is 67 mol/s, while the standard error of the mean at 95% CL is large, i.e. ±60%. Given the results for CO2 and CO for the same flight data, we conclude that this much larger scatter in the observed CH4 emission rate is most likely due to variability of CH4 emissions, suggesting that the assumption of constant daily emissions is not correct for CH4 sources. This work shows that repeated measurements using aircraft-based mass balance methods can yield sufficient precision of the mean to inform emissions reduction efforts by detecting changes over time in urban emissions

    BiofOmics: A Web Platform for the Systematic and Standardized Collection of High-Throughput Biofilm Data

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    Background: Consortia of microorganisms, commonly known as biofilms, are attracting much attention from the scientific community due to their impact in human activity. As biofilm research grows to be a data-intensive discipline, the need for suitable bioinformatics approaches becomes compelling to manage and validate individual experiments, and also execute inter-laboratory large-scale comparisons. However, biofilm data is widespread across ad hoc, non-standardized individual files and, thus, data interchange among researchers, or any attempt of cross-laboratory experimentation or analysis, is hardly possible or even attempted. Methodology/Principal findings This paper presents BiofOmics, the first publicly accessible Web platform specialized in the management and analysis of data derived from biofilm high-throughput studies. The aim is to promote data interchange across laboratories, implementing collaborative experiments, and enable the development of bioinformatics tools in support of the processing and analysis of the increasing volumes of experimental biofilm data that are being generated. BiofOmics data deposition facility enforces data structuring and standardization, supported by controlled vocabulary. Researchers are responsible for the description of the experiments, their results and conclusions. BiofOmics curators interact with submitters only to enforce data structuring and the use of controlled vocabulary. Then, BiofOmics search facility makes publicly available the profile and data associated with a submitted study so that any researcher can profit from these standardization efforts to compare similar studies, generate new hypotheses to be tested or even extend the conditions experimented in the study. Significance BiofOmics novelty lays on its support to standardized data deposition, the availability of computerizable data files and the free-of-charge dissemination of biofilm studies across the community. Hopefully, this will open promising research possibilities, namely: the comparison of results between different laboratories, the reproducibility of methods within and between laboratories, and the development of guidelines and standardized protocols for biofilm formation devices and analytical methods.The financial support from the Institute of Biotechnology and Bioengineering - Center of Biological Engineering (IBB-CEB), Fundacao para a Ciencia e Tecnologia (FCT) and European Community fund FEDER (Program COMPETE), project PTDC/SAU-ESA/646091/2006/FCOMP-01-0124-FEDER-007480 and PhD grant of Idalina Machado (SFRH/BD/31065/2006) are gratefully acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

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    Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

    Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors

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    SARS-CoV-2 antibody levels can be used to assess humoral immune responses following SARS-CoV-2 infection or vaccination, and may predict risk of future infection. From cross-sectional antibody testing of 9,361 individuals from TwinsUK and ALSPAC UK population-based longitudinal studies (jointly in April-May 2021, and TwinsUK only in November 2021-January 2022), we tested associations between antibody levels following vaccination and: (1) SARS-CoV-2 infection following vaccination(s); (2) health, socio-demographic, SARS-CoV-2 infection and SARS-CoV-2 vaccination variables. Within TwinsUK, single-vaccinated individuals with the lowest 20% of anti-Spike antibody levels at initial testing had 3-fold greater odds of SARS-CoV-2 infection over the next six to nine months, compared to the top 20%. In TwinsUK and ALSPAC, individuals identified as at increased risk of COVID-19 complication through the UK "Shielded Patient List" had consistently greater odds (2 to 4-fold) of having antibody levels in the lowest 10%. Third vaccination increased absolute antibody levels for almost all individuals, and reduced relative disparities compared with earlier vaccinations. These findings quantify the association between antibody level and risk of subsequent infection, and support a policy of triple vaccination for the generation of protective antibodies

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
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