Human Adipose Stem Cells: From Bench to Bed-Side

Stem cell-based therapies for repair and regeneration of different tissues are becoming more important in the treatment of several diseases. Adult stem cells currently symbolize the most available source of cell progenitors for tissue engineering and repair and can be harvested using minimally invasive procedures. Moreover, mesenchymal stem cells (MSCs), the most widely used stem cells in stem cell-based therapies, are multipotent progenitors, with capability to differentiate into cartilage, bone, connective, muscle, and adipose tissue. So far, bone marrow has been regarded as the main source of MSCs. To date, human adult adipose tissue may be the best suitable alternative source of MSCs. Adipose stem cells (ASCs) can be largely extracted from subcutaneous human adult adipose tissue. A large number of studies show that adipose tissue contains a biologically and clinically interesting heterogeneous cell population called stromal vascular fraction (SVF). The SVF may be employed directly or cultured for selection and expansion of an adherent population, so called adipose-derived stem cells (ASCs). In recent years, literature based on data related to SVF cells and ASCs has augmented considerably: These studies have demonstrated the efficacy and safety of SVF cells and ASCs in vivo in animal models. On the basis of these observations, in several countries, various clinical trials involving SVF cells and ASCs have been permitted. This review aims at summarizing data regarding either ASCs cellular biology or ASCs-based clinical trials and at discussing the possible future clinical translation of ASCs and their potentiality in cell-based tissue engineering

A population of luminous accreting black holes with hidden mergers

Major galaxy mergers are thought to play an important part in fuelling the growth of supermassive black holes. However, observational support for this hypothesis is mixed, with some studies showing a correlation between merging galaxies and luminous quasars and others showing no such association. Recent observations have shown that a black hole is likely to become heavily obscured behind merger-driven gas and dust, even in the early stages of the merger, when the galaxies are well separated (5 to 40 kiloparsecs). Merger simulations further suggest that such obscuration and black-hole accretion peaks in the final merger stage, when the two galactic nuclei are closely separated (less than 3 kiloparsecs). Resolving this final stage requires a combination of high-spatial-resolution infrared imaging and high-sensitivity hard-X-ray observations to detect highly obscured sources. However, large numbers of obscured luminous accreting supermassive black holes have been recently detected nearby (distances below 250 megaparsecs) in X-ray observations. Here we report high-resolution infrared observations of hard-X-ray-selected black holes and the discovery of obscured nuclear mergers, the parent populations of supermassive-black-hole mergers. We find that obscured luminous black holes (bolometric luminosity higher than 2x10^44 ergs per second) show a significant (P<0.001) excess of late-stage nuclear mergers (17.6 per cent) compared to a sample of inactive galaxies with matching stellar masses and star formation rates (1.1 per cent), in agreement with theoretical predictions. Using hydrodynamic simulations, we confirm that the excess of nuclear mergers is indeed strongest for gas-rich major-merger hosts of obscured luminous black holes in this final stage.Comment: To appear in the 8 November 2018 issue of Nature. This is the authors' version of the wor

Superconductivity at 44 K in K intercalated FeSe system with excess Fe

We report here that a new superconducting phase with much higher Tc has been found in K intercalated FeSe compound with excess Fe. We successfully grew crystals by precisely controlling the starting amount of Fe. Besides the superconducting (SC) transition at ~30 K, we observed a sharp drop in resistivity and a kink in susceptibility at 44 K. By combining thermodynamic measurements with electron spin resonance (ESR), we demonstrate that this is a new SC transition. Structural analysis unambiguously reveals two phases coexisting in the crystals, which are responsible respectively for the SC transitions at 30 and 44 K. The structural experiments and first-principles calculations consistently indicate that the 44 K SC phase is close to a 122 structure, but with an unexpectedly large c-axis of 18.10 {\AA}. We further find a novel monotonic dependence of the maximum Tc on the separation of neighbouring FeSe layers.Comment: 15 pages, 5 figure

Plastisol Foaming Process. Decomposition of the Foaming Agent, Polymer Behavior in the Corresponding Temperature Range and Resulting Foam Properties

The decomposition of azodicarbonamide, used as foaming agent in PVC - plasticizer (1/1) plastisols was studied by DSC. Nineteen different plasticizers, all belonging to the ester family, two being polymeric (polyadipates), were compared. The temperature of maximum decomposition rate (in anisothermal regime at 5 K min-1 scanning rate), ranges between 434 and 452 K. The heat of decomposition ranges between 8.7 and 12.5 J g -1. Some trends of variation of these parameters appear significant and are discussed in terms of solvent (matrix) and viscosity effects on the decomposition reactions. The shear modulus at 1 Hz frequency was determined at the temperature of maximum rate of foaming agent decomposition, and differs significantly from a sample to another. The foam density was determined at ambient temperature and the volume fraction of bubbles was used as criterion to judge the efficiency of the foaming process. The results reveal the existence of an optimal shear modulus of the order of 2 kPa that corresponds roughly to plasticizer molar masses of the order of 450 ± 50 g mol-1. Heavier plasticizers, especially polymeric ones are too difficult to deform. Lighter plasticizers such as diethyl phthalate (DEP) deform too easily and presumably facilitate bubble collapse

Helsinki-Vantaan lentoaseman tilannekuvakeskus : Häiriö- ja poikkeamatilanteiden eteneminen lentoasemalla

Tämän opinnäytetyön tavoitteena oli selvittää, miten Finavian ylläpitämällä Helsinki-Vantaa lentoasemalla tapahtuvat häiriö- ja poikkeamatilanteet vaikuttavat lentoasemalla toimiviin Finavian omiin organisaatioihin sekä lentoasemalla toimiviin viranomaisiin. Häiriö- ja poikkeamatilanteella tarkoitetaan lentoaseman normaaliin toimintaan häiritsevästi vaikuttavaa tapahtumaa, esimerkiksi sähkökatkoa. Työ tehtiin Helsinki-Vantaa lentoaseman tilannekuvakeskuksen päällikön pyynnöstä. Tilannekuvakeskuksessa huomattiin, että vaikka häiriö- ja poikkeamatilanteessa toiminta eri tahojen kanssa on ollut kitkatonta ja sujuvaa, ei toisen organisaation sisällä tapahtuvasta toiminnasta ollut kuvaa. Työn avulla selvitettiin, onko häiriö- tai poikkeamatilanteella vaikutusta eri organisaatioiden ja viranomaisten toimintaan. Opinnäytetyö auttaa rakentamaan kokonaiskäsitystä poikkeamatilanteiden aiheuttamasta toiminnasta koko lentoaseman alueella. Tätä kautta voidaan myös lisätä ymmärrystä eri organisaatioiden ja viranomaisten välillä. Opinnäytetyö toteutettiin yhteistyössä Helsinki-Vantaa lentoaseman tilannekuvakeskuksen kanssa. Työn edetessä rakennetta muokattiin yhteistyössä tilaajan kanssa niin, että se palvelisi mahdollisimman tarkoituksenmukaisesti eri organisaatioita. Työ toteutettiin tekemällä laadullinen tutkimus, jonka runkona oli puolistrukturoitu haastattelu. Haastatteluita kertyi yhteensä 19 kappaletta ja haastateltavia 21. Haastateltavina olivat Finavian eri organisaatioiden johtajia tai päälliköitä ja lentoaseman toimintaan liittyvien viranomaisten lentoaseman toimipisteiden päälliköt. Työstä rajattiin pois kaupalliset yritykset, koska haastatteluiden määrä olisi kasvanut liian suureksi. Lentoaseman tilannekuvakeskus on luonut useita valmiita toimintamalleja erilaisiin häiriö- ja poikkeamatilanteisiin. Tilannekuvakeskuksen päällikkö valitsi näistä häiriö- ja poikkeamatilanteista ne, jotka ovat todennäköisiä tai merkittäviä ja vaikuttavat haitallisesti lentoaseman toimintaan. Erilaisia häiriö- ja poikkeamatilanteita valikoitui 17 kappaletta. Näiden tilanteiden vaikutuksia ja toimintamalleja käsiteltiin haastatteluissa. Haastatteluissa saatu informaatio liitettiin tilannekuvakeskuksen toimintamalleihin ja luotiin jokaiseen valittuun poikkeamatilanteeseen kronologinen kuvaus eri organisaatioiden toiminnasta. Opinnäytetyöstä on myöhemmin tarkoitus tehdä pelkistetympi käsikirja Finavian ja viranomaisten käyttöön.The aim of this study was to find out how to Finavia’s Helsinki-Vantaa airport take place in crisis and emergency situations and how they affecting operating at the airport Finavia's own organizations as well as authorities operating at the airport. The work was done at the request of the Head of the Helsinki-Vantaa airport operation center. The airport operation center noted that although the crisis and emergency situations operation with various parties has been smooth, but nobody didn’t have a picture how these crisis and emergency situations was handled in the another organizations. The work purpose was to find out whether the fault or deviation situation could affect the functioning of the various organizations and public authorities. The thesis helps to build the overall understanding of the actions caused by the deviation of situations throughout the airport. This period may also increase the understanding of the different organizations and authorities. The research was conducted in cooperation with the Helsinki-Vantaa airport operation center. As work progresses, the structure was modified in cooperation with the client so that it would serve as appropriately as possible the different organizations. The work was carried out by qualitative research, whose backbone was the semi-structured interview. Interviews were a total of 19 tracks and 21 interviewees were interviewed leaders or managers in different organizations and Finavia's airport activities related to airport authorities, heads of offices. Work were excluded trading companies, because the number of interviews had grown too large. The airport operation center has created a number of ready-made models for different crisis and emergency situations. Head of the Centre chose a snapshot of the crisis and emergency situations, those who are likely or significant and adversely affect the operation of the airport. 17 various types of crisis and emergency situations was selected. Effects and models of these situations addressed in the interviews. The information obtained in the interviews attached a airport operation center’s operational models and was created for each selected deviation situation chronological description of the activities of various organizations. The thesis is later to be made simpler manual for use by Finavia and the authorities

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Differential regulation of neurotrophin expression in human bronchial smooth muscle cells

BACKGROUND: Human bronchial smooth muscle cells (HBSMC) may regulate airway inflammation by secreting cytokines, chemokines and growth factors. The neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), have been shown to be elevated during airway inflammation and evoke airway hyperresponsiveness. We studied if HBSMC may be a source of NGF, BDNF and NT-3, and if so, how inflammatory cytokines may influence their production. METHODS: Basal and cytokine (IL-1β, IFN-γ, IL-4)-stimulated neurotrophin expression in HBSMC cultured in vitro was quantified. The mRNA expression was quantified by real-time RT-PCR and the protein secretion into the cell culture medium by ELISA. RESULTS: We observed a constitutive NGF, BDNF and NT-3 expression. IL-1β stimulated a transient increase of NGF, while the increase of BDNF had a later onset and was more sustained. COX-inhibitors (indomethacin and NS-398) markedly decreased IL-1β-stimulated secretion of BDNF, but not IL-1β-stimulated NGF secretion. IFN-γ increased NGF expression, down-regulated BDNF expression and synergistically enhanced IL-1β-stimulated NGF expression. In contrast, IL-4 had no effect on basal NGF and BDNF expression, but decreased IL-1β-stimulated NGF expression. NT-3 was not altered by the tested cytokines. CONCLUSION: Taken together, our data indicate that, in addition to the contractile capacity, HBSMC can express NGF, BDNF and NT-3. The expression of these neurotrophins may be differently regulated by inflammatory cytokines, suggesting a dynamic interplay that might have a potential role in airway inflammation

Chemosensitization by phenothiazines in human lung cancer cells: impaired resolution of γH2AX and increased oxidative stress elicit apoptosis associated with lysosomal expansion and intense vacuolation

Chemotherapy resistance poses severe limitations on the efficacy of anti-cancer medications. Recently, the notion of using novel combinations of ‘old' drugs for new indications has garnered significant interest. The potential of using phenothiazines as chemosensitizers has been suggested earlier but so far our understanding of their molecular targets remains scant. The current study was designed to better define phenothiazine-sensitive cellular processes in relation to chemosensitivity. We found that phenothiazines shared the ability to delay γH2AX resolution in DNA-damaged human lung cancer cells. Accordingly, cells co-treated with chemotherapy and phenothiazines underwent protracted cell-cycle arrest followed by checkpoint escape that led to abnormal mitoses, secondary arrest and/or a form of apoptosis associated with increased endogenous oxidative stress and intense vacuolation. We provide evidence implicating lysosomal dysfunction as a key component of cell death in phenothiazine co-treated cells, which also exhibited more typical hallmarks of apoptosis including the activation of both caspase-dependent and -independent pathways. Finally, we demonstrated that vacuolation in phenothiazine co-treated cells could be reduced by ROS scavengers or the vacuolar ATPase inhibitor bafilomycin, leading to increased cell viability. Our data highlight the potential benefit of using phenothiazines as chemosensitizers in tumors that acquire molecular alterations rendering them insensitive to caspase-mediated apoptosis

Euphol, a tetracyclic triterpene, from Euphorbia tirucalli induces autophagy and sensitizes temozolomide cytotoxicity on glioblastoma cells

Glioblastoma (GBM) is the most frequent and aggressive type of brain tumor. There are limited therapeutic options for GBM so that new and effective agents are urgently needed. Euphol is a tetracyclic triterpene alcohol, and it is the main constituent of the sap of the medicinal plant Euphorbia tirucalli. We previously identified anti-cancer activity in euphol based on the cytotoxicity screening of 73 human cancer cells. We now expand the toxicological screening of the inhibitory effect and bioactivity of euphol using two additional glioma primary cultures. Euphol exposure showed similar cytotoxicity against primary glioma cultures compared to commercial glioma cells. Euphol has concentration-dependent cytotoxic effects on cancer cell lines, with more than a five-fold difference in the IC50 values in some cell lines. Euphol treatment had a higher selective cytotoxicity index (0.64-3.36) than temozolomide (0.11-1.13) and reduced both proliferation and cell motility. However, no effect was found on cell cycle distribution, invasion and colony formation. Importantly, the expression of the autophagy-associated protein LC3-II and acidic vesicular organelle formation were markedly increased, with Bafilomycin A1 potentiating cytotoxicity. Finally, euphol also exhibited antitumoral and antiangiogenic activity in vivo, using the chicken chorioallantoic membrane assay, with synergistic temozolomide interactions in most cell lines. In conclusion, euphol exerted in vitro and in vivo cytotoxicity against glioma cells, through several cancer pathways, including the activation of autophagy-associated cell death. These findings provide experimental support for further development of euphol as a novel therapeutic agent for GBM, either alone or in combination chemotherapy.The work was supported by the Amazonia Fitomedicamentos (FITO05/2012) Ltda. and Barretos Cancer Hospital, all from Brazil

Renal replacement therapy in acute kidney injury: controversy and consensus

Renal replacement therapies (RRTs) represent a cornerstone in the management of severe acute kidney injury. This area of intensive care and nephrology has undergone significant improvement and evolution in recent years. Continuous RRTs have been a major focus of new technological and treatment strategies. RRT is being used increasingly in the intensive care unit, not only for renal indications but also for other organ-supportive strategies. Several aspects related to RRT are now well established, but others remain controversial. In this review, we review the available RRT modalities, covering technical and clinical aspects. We discuss several controversial issues, provide some practical recommendations, and where possible suggest a research agenda for the future