391 research outputs found
Katsaus polttotaisteluaineisiin ja -välineisiin sekä polttosuojeluun
Artikkelin alussa luodaan historiallinen katsaus tulen käyttöön taistelussa, mutta artikkelin tarkoituksena on esittää "koottuna niitä tietoja polttotaisteluaineista, polttotaisteluvälineistä ja polttosuojelusta, mitä tuoreimmista kirjallisista lähteistä on löytynyt". Ensimmäisessä luvussa esitellään polttotaisteluaineet, käsitellen ensin napalm, sen kehitys, käytössä olevat napalmit, napalmin ominaisuudet sekä napalmhyytelön valmistaminen kenttäoloissa. Muista polttotaisteluaineista esitellään ominaisuudet ja käyttötarkoituksia. Esittelyssä ovat valkoinen fosfori, magnesium ja termiitti sekä eräitä muita apuaineita.Toisessa luvussa, "Polttotaisteluvälineet", esitellään napalmpommin kehitysvaiheita, pommin rakennetta ja sen vaikutuksia. Lisäksi esitellään magnesiumpommin rakenne ja toimintaperiaate esimerkkinä muiden polttotaisteluaineiden käyttövälineenä. Luvun lopussa esitellään erilaisia kevyitä ja ajoneuvoasenteisia liekinheittimiä ominaisuuksineen sekä taistelukentällä rakennettavia polttotaisteluvälineitä. Kolmas luku käsittelee polttosuojelua. Siinä käsitellään ensin joukkokohtaisen polttosuojelun eri tekijöitä, kuten koulutusta, suojautumista ja sammutustoimintaa. Luvun lopussa tarkastellaan omakohtaista polttosuojelua; suojautumista ja ensiapua. Yhdistelmässä muun muassa todetaan, että kynnys polttotaisteluvälineiden käyttöön on matalammalla, kuin ydinaseen ja taistelukaasujen käyttö, joten niiden käyttöön on syytä varautua. There is summary in English at the end of the article
Anticancer activity of the protein kinase C modulator HMI-1a3 in 2D and 3D cell culture models of androgen-responsive and androgen-unresponsive prostate cancer
Prostate cancer is one of the most common cancers in men. Although it has a relatively high 5-year survival rate, development of resistance to standard androgen-deprivation therapy is a significant clinical problem. Therefore, novel therapeutic strategies are urgently needed. The protein kinase C (PKC) family is a putative prostate cancer drug target, but so far no PKC-targeting drugs are available for clinical use. By contrast to the standard approach of developing PKC inhibitors, we have developed isophthalate derivatives as PKC agonists. In this study, we have characterized the effects of the most potent isophthalate, 5-(hydroxymethyl) isophthalate 1a3 (HMI-1a3), on three prostate cancer cell lines (LNCaP, DU145, and PC3) using both 2D and 3D cell culture models. In 2D cell culture, HMI-1a3 reduced cell viability or proliferation in all cell lines as determined by the metabolic activity of the cells (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay) and thymidine incorporation. However, the mechanism of action in LNCaP cells was different to that in DU145 or PC3 cells. In LNCaP cells, HMI-1a3 induced a PKC-dependent activation of caspase 3/7, indicating an apoptotic response, whereas in DU145 and PC3 cells, it induced senescence, which was independent of PKC. This was observed as typical senescent morphology, increased beta-galactosidase activity, and upregulation of the senescence marker p21 and downregulation of E2F transcription factor 1. Using a multicellular spheroid model, we further showed that HMI-1a3 affects the growth of LNCaP and DU145 cells in a 3D culture, emphasizing its potential as a lead compound for cancer drug development.Peer reviewe
Protein kinase C-activating isophthalate derivatives mitigate Alzheimer's disease-related cellular alterations
Abnormal protein kinase C (PKC) function contributes to many pathophysiological processes relevant for Alzheimer's disease (AD), such as amyloid precursor protein (APP) processing. Phorbol esters and other PKC activators have been demonstrated to enhance the secretion of soluble APP alpha (sAPP alpha), reduce the levels of beta-amyloid (A beta), induce synaptogenesis, and promote neuroprotection. We have previously described isophthalate derivatives as a structurally simple family of PKC activators. Here, we characterised the effects of isophthalate derivatives HMI-1a3 and HMI-1b11 on neuronal viability, neuroinflammatory response, processing of APP and dendritic spine density and morphology in in vitro. HMI-1a3 increased the viability of embryonic primary cortical neurons and decreased the production of the pro-inflammatory mediator TNF alpha, but not that of nitric oxide, in mouse neuron-BV2 microglia co-cultures upon LPS- and IFN-gamma-induced neuroinflammation. Furthermore, both HMI-1a3 and HMI-1b11 increased the levels of sAPPa relative to total sAPP and the ratio of A beta 42/A beta 40 in human SH-Sv5v neuroblastoma cells. Finally, bryostatin-1, but not HMI-1a3, increased the number of mushroom spines in proportion to total spine density in mature mouse hippocampal neuron cultures. These results suggest that the PKC activator HMI-1a3 exerts neuroprotective functions in the in vitro models relevant for AD by reducing the production of TNF alpha and increasing the secretion of neuroprotective sAPPa.Peer reviewe
Missing Selectivity of Targeted 4 beta-Phorbol Prodrugs Expected to be Potential Chemotherapeutics
Targeting cytotoxic 4 beta-phorbol esters toward cancer tissue was attempted by conjugating a 4 beta-pborbol derivative with substrates for the proteases prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) expressed in cancer tissue. The hydrophilic peptide moiety was hypothesized to prevent penetration of the prodrugs into cells and prevent interaction with PKC. Cleavage of the peptide in cancer tumors was envisioned to release lipophilic cytotoxins, which subsequently penetrate into cancer cells. The 4 beta-phorbol esters were prepared from 4 beta-phorbol isolated from Croton tiglium seeds, while the peptides were prepared by solid-phase synthesis. Cellular assays revealed activation of PKC by the prodrugs and efficient killing of both peptidase positive as well as peptidase negative cells. Consequently no selectivity for enzyme expressing cells was found.Peer reviewe
Internal phosphorus load estimation during biomanipulation in a large polymictic and mesotrophic lake
We quantified internal phosphorus (P) load for 26 years in the polymictic, large (155 km2) and shallow (mean depth 5.5 m) Lake Säkylän Pyhäjärvi, which was heavily biomanipulated by fish removal. Internal load was estimated as (1) partially net estimates from in situ P summer increases, (2) net estimates from P budgets (mass balance approach), and (3) gross estimates from predicted active sediment release area and sediment P release, dependent on August lake temperature. Long-term averages of these estimates were similar and large at about 60% of average external load (105 mg m–2 yr–1) and were larger than external load in years with high water temperature and low water load. Regression analysis revealed that external load is decreasing but internal load is increasing over time. Internal load was negatively correlated with annual water load and positively correlated with lake water temperature. Long-term average annual or summer P concentrations are adequately predicted by a P mass balance model that includes external load, internal load (Method 3), and sedimentation as independently predicted retention. Predictability was poor for individual years, however, partially due to the poor correlation of observed lake and outflow P concentrations, the variable abundance of planktivorous fish, and reflecting the violation of the steady state assumption when individual years are modeled. Scenario modeling shows that biomanipulation cancels out the effects of internal load and forecasts a rapid increase of internal load and P concentration due to climate change; therefore, measures that further decrease external and internal P load and strengthen biomanipulation are recommended
Why we can no longer ignore consecutive disasters
In recent decades, a striking number of countries have suffered from consecutive disasters: events whose impacts overlap both spatially and temporally, while recovery is still under way. The risk of consecutive disasters will increase due to growing exposure, the interconnectedness of human society, and the increased frequency and intensity of nontectonic hazard. This paper provides an overview of the different types of consecutive disasters, their causes, and impacts. The impacts can be distinctly different from disasters occurring in isolation (both spatially and temporally) from other disasters, noting that full isolation never occurs. We use existing empirical disaster databases to show the global probabilistic occurrence for selected hazard types. Current state‐of‐the art risk assessment models and their outputs do not allow for a thorough representation and analysis of consecutive disasters. This is mainly due to the many challenges that are introduced by addressing and combining hazards of different nature, and accounting for their interactions and dynamics. Disaster risk management needs to be more holistic and codesigned between researchers, policy makers, first responders, and companies
Limnocnida tanganyicae medusae (Cnidaria: Hydrozoa): a semiautonomous microcosm in the food web of Lake Tanganyika
Medusae are important members of marine food webs, but are rare in lakes. In one of the largest lakes in the world, Lake Tanganyika, a small medusa (Limnocnida tanganyicae) is a prominent component of zooplankton. We used field and laboratory methods to study the ecological role of Lake Tanganyika medusae, which occasionally reached high local densities in the whole epilimnion. The largest individuals showed low amplitude, diel vertical migration which minimized their exposure to harmful UV radiation and also may be important for picocyanobacteria regularly present in the medusae. The endosymbiotic picocyanobacteria differed morphologically among medusae and were predominantly one Lake Biwa type Cyanobium sp. that typically was abundant in the water column. Under light, some medusae were net primary producers. Although nitrogen stable isotopic ratios indicated that the free-living cyanobacteria were nitrogen-fixers, the picocyanobacteria in medusae obtained nitrogen predominantly from their host. Stable isotopic ratios of carbon and nitrogen further suggested that copepods were the most likely prey for the medusae. Lake Tanganyika medusae apparently base their metabolism both on animal and plant sources, with possible internal cycling of nutrients; however, the role of picocyanobacteria gardening in the Lake Tanganyika ecosystem and its medusae requires quantification
Moderate and heavy metabolic stress interval training improve arterial stiffness and heart rate dynamics in humans
Traditional continuous aerobic exercise training attenuates age-related increases of arterial stiffness, however, training studies have not determined whether metabolic stress impacts these favourable effects. Twenty untrained healthy participants (n = 11 heavy metabolic stress interval training, n = 9 moderate metabolic stress interval training) completed 6 weeks of moderate or heavy intensity interval training matched for total work and exercise duration. Carotid artery stiffness, blood pressure contour analysis, and linear and non-linear heart rate variability were assessed before and following training. Overall, carotid arterial stiffness was reduced (p 0.05). This study demonstrates the effectiveness of interval training at improving arterial stiffness and autonomic function, however, the metabolic stress was not a mediator of this effect. In addition, these changes were also independent of improvements in aerobic capacity, which were only induced by training that involved a high metabolic stress
Uso de iodóforo tópico em feridas crônicas: revisão da literatura
La investigación trata de una revisión de la literatura a cerca de la utilización del yodo tópico y/o compuestos en el tratamiento de las heridas crónicas. Se buscaran los ensayos clínicos en el Cochrane. Catorce (n=24) publicaciones estaban de acuerdo con los criterios de inclusión, y fueran analizadas según las características de las revistas y ensayos y clasificadas como: yodo versus otros agentes tópicos (7/ 50%); yodo versus curativos (6/ 42,9%) y yodo versus sin yodo (1/ 7,1%). Fueran obtenidos resultados favorables a la utilización del yodo y/o compuestos en 50% de los artículos analizados. Cuanto a las tendencias de los resultados, 6 de 8 publicaciones, a cerca de la de cicatrización de las heridas y prevención de infección, fueran favorables; 4 de 5 fueran no favorables solamente para la cicatrización, y el resultado del único trabajo con indicación del uso para tratamiento de infección de herida fue no favorable.Trata-se de revisão de literatura relacionada ao uso de iodóforos tópicos no tratamento de feridas crônicas. Os ensaios clínicos foram localizados por meio da Base de Dados Cochrane de Revisões Sistemáticas e Registro Cochrane Central de Ensayos Controlados. Quatorze (58,3%), dentre 24 artigos, atenderam os critérios de inclusão, analisados quanto às características dos periódicos e dos estudos e classificados em três grupos: iodóforo versus outros agentes tópicos (7 ou 50%); iodóforo versus coberturas (6 ou 42,9%) e iodóforo versus sem iodóforo (1 ou 7,1%). Resultados favoráveis à utilização dos iodóforos ocorreram em 50% dos artigos analisados. Quanto às tendências dos resultados, seis, dentre oito artigos, que tratavam de cicatrização de feridas e prevenção de infecção, foram favoráveis; quatro, dentre cinco, foram desfavoráveis somente para a cicatrização e no único ensaio em que houve indicação do seu uso para tratamento de infecção de ferida o resultado foi desfavorável.This study aimed to do a review of the literature regarding the use of topic iodine and/or compounds in the treatment of chronic wounds. The clinical trials were searched in the Cochrane database. Fourteen (58.3%) among 24 studies fulfilled the inclusion criteria. The articles were analyzed regarding journal and study characteristics and classified into three groups: Iodine versus other topic agents (7/ 50%); Iodine versus different dressings (6/ 42.9%); Iodine versus without Iodine (1/ 7.1%). Favorable results for the use of Iodine or similar product occurred in 50% of the analyzed studies. Six out of 8 trials showed favorable results for healing and infection prevention/ treatment; 4 out of 5 were not favorable when the healing objective was investigated and 1 study for infection treatment showed no favorable result
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