Analyses of chondrogenic induction of adipose mesenchymal stem cells by combined co-stimulation mediated by adenoviral gene transfer

INTRODUCTION: Adipose-derived stem cells (ASCs) have the potential to differentiate into cartilage under stimulation with some reported growth and transcriptional factors, which may constitute an alternative for cartilage replacement approaches. In this study, we analyzed the in vitro chondrogenesis of ASCs transduced with adenoviral vectors encoding insulin-like growth factor-1 (IGF-1), transforming growth factor beta-1 (TGF-β1), fibroblast growth factor-2 (FGF-2), and sex-determining region Y-box 9 (SOX9) either alone or in combinations. METHODS: Aggregate cultures of characterized ovine ASCs were transduced with 100 multiplicity of infections of Ad.IGF-1, Ad.TGF-β1, Ad.FGF-2, and Ad.SOX9 alone or in combination. These were harvested at various time points for detection of cartilage-specific genes expression by quantitative real-time PCR or after 14 and 28 days for histologic and biochemical analyses detecting proteoglycans, collagens (II, I and X), and total sulfated glycosaminoglycan and collagen content, respectively. RESULTS: Expression analyses showed that co-expression of IGF-1 and FGF-2 resulted in higher significant expression levels of aggrecan, biglycan, cartilage matrix, proteoglycan, and collagen II (all P ≤0.001 at 28 days). Aggregates co-transduced with Ad.IGF-1/Ad.FGF-2 showed a selective expression of proteoglycans and collagen II, with limited expression of collagens I and × demonstrated by histological analyses, and had significantly greater glycosaminoglycan and collagen production than the positive control (P ≤0.001). Western blot analyses for this combination also demonstrated increased expression of collagen II, while expression of collagens I and × was undetectable and limited, respectively. CONCLUSION: Combined overexpression of IGF-1/FGF-2 within ASCs enhances their chondrogenic differentiation inducing the expression of chondrogenic markers, suggesting that this combination is more beneficial than the other factors tested for the development of cell-based therapies for cartilage repair

Supporting collaborative improvement of resources in the Khresmoi health information system

Since medical knowledge relies on both scientific knowledge and real-life experience, the importance of user contributions to improve resources in health systems cannot be underestimated. We present work from the Khresmoi project which aims to develop a multilingual multimodal search and access system for biomedical information and documents. Khresmoi targets three distinct user classes with differing levels of medical knowledge and information requirements, namely: general public, general practitioners, and, as an example of an area of clinical expertise, radiologists. The Khresmoi system will provide these users with valuable (whose quality has been evaluated and approved) and enriched (meta information from biomedical knowledge bases is added) medical information, selected to fit their medical knowledge and their preferred language. The system will include novel collaborative components of the system are designed to provide means for users to contribute to the system’s knowledge by adding or correcting annotations to the documents, as well as a collaborative platform where they will be able to share their own files and both annotate and discuss them

Gorputz adierazpena lehen hezkuntzan

Liburu honekin zera nahi dugu: Gorputz Hezkuntzako curriculuma ezagutzea, legeak dioena eta eduki multzoen garapena. Eta era berean, motrizitatearen lan metodologiak eta irakasle gisa eskura ditugun baliabideak ezagutzea da.Material honen helburua da Lehen Hezkuntzako Irakasle ikasketetan enborrezko izan den Gorputz Adierazpena irakasgaiaren edukiak zabaltzea du helburu. Hala, Graduko ikasketetan Gorputz Hezkuntzako minorrean hautazkoa izango den Gorputz Adierazpena ikasgairako oinarria izango diren edukiak zabaltzea. Ikasmaterial honek hainbat atal nagusiak ditu: Lehenengo atalean, Gorputz Adierazpenaren kontzeptua, historia eta korronte ideiologikoak aztertzen dira lehen kapituluan. Bigarrenean, Gorputz Adierazpenaren trataera LOE legean eta aurreko legetan, eta honene arabera unibertsitateik gorputz adierazpena lantzeko egiten den proposamen zehatz bat. Hirugarren kapitulutik zazpigarrenera eduki bakoitza aztertzen da (gerturatze teorikoa eta handik unitate didaktiko zehatz bat sortzen da. Bertan, ikasle bakoitzak aipatzen du zer gertatu den praktikara eraman duenean bere proposamena).Ikasmaterial honek hainbat atal nagusiak ditu: Lehenengo atalean, Gorputz Adierazpenaren kontzeptua, historia eta korronte ideiologikoak aztertzen dira lehen kapituluan. Bigarrenean, Gorputz Adierazpenaren trataera LOE legean eta aurreko legetan, eta honene arabera unibertsitateik gorputz adierazpena lantzeko egiten den proposamen zehatz bat. Hirugarren kapitulutik zazpigarrenera eduki bakoitza aztertzen da (gerturatze teorikoa eta handik unitate didaktiko zehatz bat sortzen da. Bertan, ikasle bakoitzak aipatzen du zer gertatu den praktikara eraman duenean bere proposamena).Ikasmaterial honek hainbat atal nagusiak ditu: Lehenengo atalean, Gorputz Adierazpenaren kontzeptua, historia eta korronte ideiologikoak aztertzen dira lehen kapituluan. Bigarrenean, Gorputz Adierazpenaren trataera LOE legean eta aurreko legetan, eta honene arabera unibertsitateik gorputz adierazpena lantzeko egiten den proposamen zehatz bat. Hirugarren kapitulutik zazpigarrenera eduki bakoitza aztertzen da (gerturatze teorikoa eta handik unitate didaktiko zehatz bat sortzen da. Bertan, ikasle bakoitzak aipatzen du zer gertatu den praktikara eraman duenean bere proposamena). Ikasmaterial honek hainbat atal nagusiak ditu: Lehenengo atalean, Gorputz Adierazpenaren kontzeptua, historia eta korronte ideiologikoak aztertzen dira lehen kapituluan. Bigarrenean, Gorputz Adierazpenaren trataera LOE legean eta aurreko legetan, eta honene arabera unibertsitateik gorputz adierazpena lantzeko egiten den proposamen zehatz bat. Hirugarren kapitulutik zazpigarrenera eduki bakoitza aztertzen da (gerturatze teorikoa eta handik unitate didaktiko zehatz bat sortzen da. Bertan, ikasle bakoitzak aipatzen du zer gertatu den praktikara eraman duenean bere proposamena).Liburu honek UPV/EHUko Euskara eta Eleaniztasuneko Errektoreordetzaren dirulaguntza jaso d

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Search for tt¯ resonances in fully hadronic final states in pp collisions at √s = 13 TeV with the ATLAS detector

This paper presents a search for new heavy particles decaying into a pair of top quarks using 139 fb of proton-proton collision data recorded at a centre-of-mass energy of s = 13 TeV with the ATLAS detector at the Large Hadron Collider. The search is performed using events consistent with pair production of high-transverse-momentum top quarks and their subsequent decays into the fully hadronic final states. The analysis is optimized for resonances decaying into a tt¯ pair with mass above 1.4 TeV, exploiting a dedicated multivariate technique with jet substructure to identify hadronically decaying top quarks using large-radius jets and evaluating the background expectation from data. No significant deviation from the background prediction is observed. Limits are set on the production cross-section times branching fraction for the new Z′ boson in a topcolor-assisted-technicolor model. The Z′ boson masses below 3.9 and 4.7 TeV are excluded at 95% confidence level for the decay widths of 1% and 3%, respectively. [Figure not available: see fulltext.

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

A note on comonotonicity and positivity of the control components of decoupled quadratic FBSDE

In this small note we are concerned with the solution of Forward-Backward Stochastic Differential Equations (FBSDE) with drivers that grow quadratically in the control component (quadratic growth FBSDE or qgFBSDE). The main theorem is a comparison result that allows comparing componentwise the signs of the control processes of two different qgFBSDE. As a byproduct one obtains conditions that allow establishing the positivity of the control process.Comment: accepted for publicatio

Dendritic Cells Take up and Present Antigens from Viable and Apoptotic Polymorphonuclear Leukocytes

Dendritic cells (DC) are endowed with the ability to cross-present antigens from other cell types to cognate T cells. DC are poised to meet polymorphonuclear leukocytes (PMNs) as a result of being co-attracted by interleukin-8 (IL-8), for instance as produced by tumor cells or infected tissue. Human monocyte-derived and mouse bone marrow-derived DC can readily internalize viable or UV-irradiated PMNs. Such internalization was abrogated at 4°C and partly inhibited by anti-CD18 mAb. In mice, DC which had internalized PMNs containing electroporated ovalbumin (OVA) protein, were able to cross-present the antigen to CD8 (OT-1) and CD4 (OT-2) TCR-transgenic T cells. Moreover, in humans, tumor cell debris is internalized by PMNs and the tumor-cell material can be subsequently taken up from the immunomagnetically re-isolated PMNs by DC. Importantly, if human neutrophils had endocytosed bacteria, they were able to trigger the maturation program of the DC. Moreover, when mouse PMNs with E. coli in their interior are co-injected in the foot pad with DC, many DC loaded with fluorescent material from the PMNs reach draining lymph nodes. Using CT26 (H-2d) mouse tumor cells, it was observed that if tumor cells are intracellularly loaded with OVA protein and UV-irradiated, they become phagocytic prey of H-2d PMNs. If such PMNs, that cannot present antigens to OT-1 T cells, are immunomagnetically re-isolated and phagocytosed by H-2b DC, such DC productively cross-present OVA antigen determinants to OT-1 T cells. Cross-presentation to adoptively transferred OT-1 lymphocytes at draining lymph nodes also take place when OVA-loaded PMNs (H-2d) are coinjected in the footpad of mice with autologous DC (H-2b). In summary, our results indicate that antigens phagocytosed by short-lived PMNs can be in turn internalized and productively cross-presented by DC