bluuebunny/crossref_metadata_2025_split huggingface dataset:
Focal Adhesion Kinase–Mediated Activation of Glycogen Synthase Kinase 3β Regulates IL-33 Receptor Internalization and IL-33 Signaling
Authors: Zhao Jing , Wei Jianxin , Bowser Rachel K. , Traister Russell S. , Fan Ming-Hui , Zhao Yutong 
Published: December 2014

Abstract
IL-33, a relatively new member of the IL-1 cytokine family, plays a crucial role in allergic inflammation and acute lung injury. Long form ST2 (ST2L), the receptor for IL-33, is expressed on immune effector cells and lung epithelia and plays a critical role in triggering inflammation. We have previously shown that ST2L stability is regulated by the ubiquitin-proteasome system; however, its upstream internalization has not been studied. In this study, we demonstrate that glycogen synthase kinase 3β (GSK3β) regulates ST2L internalization and IL-33 signaling. IL-33 treatment induced ST2L internalization, and an effect was attenuated by inhibition or downregulation of GSK3β. GSK3β was found to interact with ST2L on serine residue 446 in response to IL-33 treatment. GSK3β binding site mutant (ST2LS446A) and phosphorylation site mutant (ST2LS442A) are resistant to IL-33–induced ST2L internalization. We also found that IL-33 activated focal adhesion kinase (FAK). Inhibition of FAK impaired IL-33–induced GSK3β activation and ST2L internalization. Furthermore, inhibition of ST2L internalization enhanced IL-33–induced cytokine release in lung epithelial cells. These results suggest that modulation of the ST2L internalization by FAK/GSK3β might serve as a unique strategy to lessen pulmonary inflammation.
JUNB Is a Key Transcriptional Modulator of Macrophage Activation
Authors: Fontana Mary F. , Baccarella Alyssa , Pancholi Nidhi , Pufall Miles A. , Herbert De’Broski R. , Kim Charles C. 
Published: December 2014

Abstract
Activated macrophages are crucial for restriction of microbial infection but may also promote inflammatory pathology in a wide range of both infectious and sterile conditions. The pathways that regulate macrophage activation are therefore of great interest. Recent studies in silico have putatively identified key transcription factors that may control macrophage activation, but experimental validation is lacking. In this study, we generated a macrophage regulatory network from publicly available microarray data, employing steps to enrich for physiologically relevant interactions. Our analysis predicted a novel relationship between the AP-1 family transcription factor Junb and the gene Il1b, encoding the pyrogen IL-1β, which macrophages express upon activation by inflammatory stimuli. Previously, Junb has been characterized primarily as a negative regulator of the cell cycle, whereas AP-1 activity in myeloid inflammatory responses has largely been attributed to c-Jun. We confirmed experimentally that Junb is required for full expression of Il1b, and of additional genes involved in classical inflammation, in macrophages treated with LPS and other immunostimulatory molecules. Furthermore, Junb modulates expression of canonical markers of alternative activation in macrophages treated with IL-4. Our results demonstrate that JUNB is a significant modulator of both classical and alternative macrophage activation. Further, this finding provides experimental validation for our network modeling approach, which will facilitate the future use of gene expression data from open databases to reveal novel, physiologically relevant regulatory relationships.
The Orientation of HIV-1 gp120 Binding to the CD4 Receptor Differentially Modulates CD4+ T Cell Activation
Authors: Zimmermann Kathrin , Liechti Thomas , Haas Anna , Rehr Manuela , Trkola Alexandra , Günthard Huldrych F. , Oxenius Annette 
Published: December 2014

Abstract
Progressive quantitative and qualitative decline of CD4+ T cell responses is one hallmark of HIV-1 infection and likely depends on several factors, including a possible contribution by the HIV-1 envelope glycoprotein gp120, which binds with high affinity to the CD4 receptor. Besides virion-associated and cell-expressed gp120, considerable amounts of soluble gp120 are found in plasma or lymphoid tissue, predominantly in the form of gp120–anti-gp120 immune complexes (ICs). Because the functional consequences of gp120 binding to CD4+ T cells are controversially discussed, we investigated how gp120 affects TCR-mediated activation of human CD4+ T cells by agonistic anti-CD3 mAb or by HLA class II–presented peptide Ags. We show that the spatial orientation of gp120–CD4 receptor binding relative to the site of TCR engagement differentially affects TCR signaling efficiency and hence CD4+ T cell activation. Whereas spatially and temporally linked CD4 and TCR triggering at a defined site promotes CD4+ T cell activation by exceeding local thresholds for signaling propagation, CD4 receptor engagement by gp120-containing ICs all around the CD4+ T cell undermine its capacity in supporting proximal TCR signaling. In vitro, gp120 ICs are efficiently captured by CD4+ T cells and thereby render them hyporesponsive to TCR stimulation. Consistent with these in vitro results we show that CD4+ T cells isolated from HIV+ individuals are covered with ICs, which at least partially contain gp120, and suggest that IC binding to CD4 receptors might contribute to the progressive decline of CD4+ T cell function during HIV-1 infection.
Association between Cancer Literacy and Cancer-Related Behaviour: Evidence from Ticino, Switzerland
Authors: Diviani Nicola , Schulz Peter J. 
Published: December 2014

Background This paper details the role of different dimensions of health literacy in the relationship between health literacy and cancer-related health behaviours. In particular, Cancer Literacy is studied as an exemplar of a dimension of health literacy beyond basic reading and writing skills. The link between functional health literacy, Cancer Literacy and cancer-related health behaviours is investigated in a sample of Ticino (Switzerland) residents (n=639). Design and methods Detailed data is collected about respondents’ functional health literacy, Cancer Literacy, cancer information seeking behaviour, engagement in cancer preventive behaviours, participation to cancer screenings, and intention to adhere to current screening recommendations. Results Results confirm the added value of Cancer Literacy – compared to functional health literacy – in explaining people's cancer information seeking behaviour, their participation to several cancer screenings and their screening intention, underscoring the need to take into account dimensions of health literacy beyond basic functional skills. Conclusions From a public health perspective, findings provide further evidence on the importance of adapting informational and educational communication intervention designed to improve cancer prevention and screening to different audiences.
Monitoring HIV-infected Patients with Diabetes: Hemoglobin A1c, Fructosamine, or Glucose?
Authors: Kim So-Young , Friedmann Patricia , Seth Amit , Fleckman Adrienne M. 
Published: December 2014

Background Published studies report inappropriately low hemoglobin A1C (HbA1c) values that underestimate glycemia in HIV patients. Methods We reviewed the charts of all HIV patients with diabetes mellitus (DM) at our clinic. Fifty-nine patients had HbA1c data, of whom 26 patients also had fructosamine data. We compared the most recent HbA1c to finger-stick (FS) glucose averaged over three months, and fructosamine to FS averaged over six weeks. Predicted average glucose (pAG) was calculated as reported by Nathan et al: pAG (mg/dL) = 28.7 × A1C% – 46.7. Data were analyzed using the Statistical Analysis System (SAS) and Kruskal–Wallis test. Results HbA1c values underestimated (UE) actual average glucose (aAG) in 19% of these patients and overestimated (OE) aAG in 27%. HbA1c estimated aAG within the established range in only 54% of the patients. There were no statistical differences in the types of HIV medication used in patients with UE, OE, or accurately estimated (AE) glycemia. A Spearman correlation coefficient between HbA1c and aAG was r = 0.53 ( P < 0.0001). Correlation between fructosamine and aAG was r = 0.47 ( P = 0.016). Conclusions The correlations between HbA1c and aAG and between fructosamine and aAG were weaker than expected, and fructosamine was not more accurate than HbA1c.
De gespleten persoonlijkheid van de massamoordenaar
Authors: van Stokkom Bas 
Published: December 2014

The split personality of the mass murderer
Compartmentalization refers to a process by which groups of people are put apart from others. In these compartments violent acts could be committed with complete impunity. Although many genocidal periods are discussed, this book is actually about the Holocaust and what the author calls ‘compartmentalization of the personality’. How can it be explained that Nazis felt no regret or guilt? What are the personality traits of these mass murderers? What are their personal motives? According to the author these criminals cannot be termed ‘ordinary people’ who were brought to killings by the situation they were in or pressure exerted on them. Individual choice and self-selection play a role.
Problemen in verband met de beperkte erfrechtelijke rechtskeuzemogelijkheid in Nederlands-Duitse verhoudingen: nu en vanaf 17 augustus 2015
Authors: Eule W. , Knot J.G. 
Published: December 2014

Problemen in verband met de beperkte erfrechtelijke rechtskeuzemogelijkheid in Nederlands-Duitse verhoudingen: nu en vanaf 17 augustus 2015
De praktijk wordt regelmatig geconfronteerd met nalatenschappen die raakvlakken hebben met zowel Duitsland als Nederland. De afwikkeling hiervan verloopt niet altijd even soepel, onder meer als gevolg van de afwijkende regels van internationaal erfrecht in Duitsland en Nederland. De rechtskeuzemogelijkheid van de erflater biedt meestal ook slechts beperkt uitkomst. In deze bijdrage worden de huidige problemen rondom toepasselijk erfrecht en rechtskeuze in Duits-Nederlandse verhoudingen in kaart gebracht en, waar mogelijk, van een (praktische) oplossing voorzien. Bovendien wordt onderzocht welke van deze problemen onder de Erfrechtverordening (vanaf 17 augustus 2015) zullen zijn opgelost en hoe met oude en nieuwe rechtskeuzes moet worden omgegaan in de Duits-Nederlandse boedelpraktijk.
In Vitro Cell Motility as a Potential Mesenchymal Stem Cell Marker for Multipotency
Authors: Bertolo Alessandro , Gemperli Armin , Gruber Marco , Gantenbein Benjamin , Baur Martin , Pötzel Tobias , Stoyanov Jivko 
Published: December 2014

Abstract
Mesenchymal stem cells (MSCs) are expected to have a fundamental role in future cell-based therapies because of their high proliferative ability, multilineage potential, and immunomodulatory properties. Autologous transplantations have the “elephant in the room” problem of wide donor variability, reflected by variability in MSC quality and characteristics, leading to uncertain outcomes in the use of these cells. We propose life imaging as a tool to characterize populations of human MSCs. Bone marrow MSCs from various donors and in vitro passages were evaluated for their in vitro motility, and the distances were correlated to the adipogenic, chondrogenic, and osteogenic differentiation potentials and the levels of senescence and cell size. Using life-image measuring of track lengths of 70 cells per population for a period of 24 hours, we observed that slow-moving cells had the higher proportion of senescent cells compared with fast ones. Larger cells moved less than smaller ones, and spindle-shaped cells had an average speed. Both fast cells and slow cells were characterized by a low differentiation potential, and average-moving cells were more effective in undergoing all three lineage differentiations. Furthermore, heterogeneity in single cell motility within a population correlated with the average-moving cells, and fast- and slow-moving cells tended toward homogeneity (i.e., a monotonous moving pattern). In conclusion, in vitro cell motility might be a useful tool to quickly characterize and distinguish the MSC population's differentiation potential before additional use.
Proceedings: Immune Tolerance and Stem Cell Transplantation: A CIRM Mini-Symposium and Workshop Report
Authors: Talib Sohel , Millan Maria T. , Jorgenson Rebecca L. , Shepard Kelly A. 
Published: December 2014

Abstract
The mission of the California Institute for Regenerative Medicine (CIRM) is to accelerate stem cell treatments to patients with unmet medical needs. Immune rejection is one hurdle that stem cell therapies must overcome to achieve a durable and effective therapeutic benefit. In July 2014, CIRM convened a group of clinical investigators developing stem cell therapeutics, immunologists, and transplantation biologists to consider strategies to address this challenge. Workshop participants discussed current approaches for countering immune rejection in the context of organ transplant and cellular therapy and defined the risks, challenges, and opportunities for adapting them to the development of stem cell-based therapeutics. This effort led to the development of a Roadmap to Tolerance for allogeneic stem cell therapy, with four fundamental steps: (a) the need to identify “tolerance-permissive” immune-suppressive regimens to enable the eventual transition from current, drug-based approaches to a newer generation of technologies for inducing tolerance; (b) testing new biologics and small molecules for inducing tolerance in stem cell-based preclinical and clinical studies; (c) stimulation of efforts to develop novel therapeutic approaches to induce central and peripheral tolerance, including manipulation of the thymus, transplantation of purified stem cells, and cell therapy with T-regulatory cells; and (d) development of robust and sensitive immune monitoring technologies for identifying biomarkers of tolerance and rejection after allogeneic stem cell treatments in the clinical setting.
Continuous generation and two‐dimensional structure of equatorial plasma bubbles observed by high‐density GPS receivers in Southeast Asia
Authors: Buhari S. M. , Abdullah M. , Hasbi A. M. , Otsuka Y. , Yokoyama T. , Nishioka M. , Tsugawa T. 
Published: December 2014

AbstractHigh‐density GPS receivers located in Southeast Asia (SEA) were utilized to study the two‐dimensional structure of ionospheric plasma irregularities in the equatorial region. The longitudinal and latitudinal variations of tens of kilometer‐scale irregularities associated with equatorial plasma bubbles (EPBs) were investigated using two‐dimensional maps of the rate of total electron content change index (ROTI) from 127 GPS receivers with an average spacing of about 50–100 km. The longitudinal variations of the two‐dimensional maps of GPS ROTI measurement on 5 April 2011 revealed that 16 striations of EPBs were generated continuously around the passage of the solar terminator. The separation distance between the subsequent onset locations varied from 100 to 550 km with 10 min intervals. The lifetimes of the EPBs observed by GPS ROTI measurement were between 50 min and over 7 h. The EPBs propagated 440–3000 km toward the east with velocities of 83–162 m s−1. The longitudinal variations of EPBs by GPS ROTI keogram coincided with the depletions of 630 nm emission observed using the airglow imager. Six EPBs were observed by GPS ROTI along the meridian of Equatorial Atmosphere Radar (EAR), while only three EPBs were detected by the EAR. The high‐density GPS receivers in SEA have an advantage of providing time continuous descriptions of latitudinal/longitudinal variations of EPBs with both high spatial resolution and broad geographical coverage. The spatial periodicity of the EPBs could be associated with a wavelength of the quasiperiodic structures on the bottomside of the F region which initiate the Rayleigh‐Taylor instability.
Modeling subsolar thermospheric waves during a solar flare and penetration electric fields
Authors: Zhu Jie , Ridley Aaron J. 
Published: December 2014

AbstractThermospheric waves occurring around the time of the 14 July 2000 solar flare were investigated using the Global Ionosphere and Thermosphere Model. The simulation results showed that extensive acoustic and gravity waves were excited by the solar flare in the subsolar region. The subsolar buoyancy period at 400 km altitude was approximately 16 min. Gravity waves with frequencies lower than the buoyancy frequency traveled from the dayside to the nightside and converged in the longitudinal region that was the antisubsolar region when the flare occurred. Acoustic waves with frequencies well above the buoyancy frequency propagated upward from approximately 130 km altitude with increasing amplitudes. The power spectra of the vertical neutral winds in the acoustic branch peaked at a period of approximately 13 min, just below the buoyancy period. The gradient in pressure was the driver of the two waves, while the ion drag caused a phase delay between the variations in the pressure gradient and the vertical velocity in the acoustic waves. An anticorrelation in the high‐frequency component of the vertical neutral wind exists between the subsolar and antisubsolar points at times away from the flare, which was driven by the rapid variations of the ion flows due to the penetration electric field. It is suggested that the penetration of the high‐latitude interplanetary magnetic field electric field to low latitudes can drive neutral waves in the equatorial region through momentum coupling with rapidly changing ion flows.
Transient small‐scale structure in the main auroral emission at Jupiter
Authors: Palmaerts B. , Radioti A. , Grodent D. , Chané E. , Bonfond B. 
Published: December 2014

AbstractThe main auroral emission at Jupiter results from the ionosphere‐magnetosphere coupling current system associated with the corotation breakdown of iogenic plasma in the current sheet. The morphology and brightness of the main auroral emission are generally suggested to be stable during time intervals of the order of an hour. Here we reveal a transient small‐scale structure in the main emission that is characterized by a localized brightness enhancement close to noon local time. The evolution of this small‐scale structure is investigated in both hemispheres on the basis of far UV images obtained with the Hubble Space Telescope between 1997 and 2007. Our observations indicate that the transient feature vary within a few tens of minutes. As one plausible explanation based on Galileo observations, we suggest that the localized enhancement of the field‐aligned currents associated with the transient structure is due to the shear induced by intermittent inward plasma flow near noon in the equatorial plane.
Crustal and upper mantle velocity structure in the vicinity of the eastern Tennessee seismic zone based upon radial P wave transfer functions
Authors: Graw Jordan H. , Powell Christine A. , Langston Charles A. 
Published: December 2014

AbstractTeleseismic transfer function analysis is used to investigate crust and upper mantle velocity structure in the vicinity of the active eastern Tennessee seismic zone (ETSZ). The ETSZ is associated with the New York‐Alabama (NY‐AL) magnetic lineament, a prominent aeromagnetic anomaly indicative of Grenville‐age, basement structure. Radial component, P wave transfer functions for 10 short‐period stations operated by the Center for Earthquake Research and Information are inverted for velocity structure. Velocity profiles are also determined for three broadband stations by converting the instrument response to that of an S‐13 short‐period seismometer. Distinct differences in the velocity profiles are found for stations located on either side of the NY‐AL magnetic lineament; velocities west of the lineament are lower than velocities to the east of the lineament in the upper 10 km and in the depth range 30 to 50 km. A gradational Moho boundary is found beneath several stations located in the Valley and Ridge province. A Moho boundary is absent at four Valley and Ridge stations located east of the magnetic lineament and south of 35.5°N.
Variability of aerosol particle number concentrations observed over the western Pacific in the spring of 2009
Authors: Takegawa N. , Moteki N. , Oshima N. , Koike M. , Kita K. , Shimizu A. , Sugimoto N. , Kondo Y. 
Published: December 2014

AbstractAirborne measurements of aerosols were conducted over the western Pacific in the spring of 2009 during the Aerosol Radiative Forcing in East Asia (A‐FORCE) aircraft campaign. The A‐FORCE flights intensively covered an important vertical‐latitudinal range in the outflow region of East Asia (0–9 km altitude; 27°N–38°N). This paper presents the variability of aerosol particle number concentrations obtained by condensation particle counters and a Single‐Particle Soot Photometer (SP2), with the focus on those in the free troposphere. The number concentration data include total condensation nuclei with particle diameters (dp) larger than 10 nm (total CN10), PM0.17‐CN10 (dp ~10–130 nm), and SP2 black carbon (NBC; dp ~75–850 nm). Large increases in total CN10 that were not associated with NBC were observed in the free troposphere, suggesting influences from new particle formation (NPF). Statistical characteristics of total CN10, PM0.17‐CN10, and NBC in the lower troposphere (LT; 0–3 km), middle troposphere (MT; 3–6 km), and upper troposphere (UT; 6–9 km) are investigated. The correlation between total CN10 and NBC, along with the ratio of PM0.17 to total CN10 and carbon monoxide mixing ratio (CO), is used to interpret the observed variability. The median concentrations of total CN10 and PM0.17‐CN10 in the UT were higher than those in the MT by a factor of ~1.4 and ~1.6, respectively. We attribute the enhancements of CN10 in the UT to NPF. Possible mechanisms affecting NPF in the free troposphere are discussed.
Statistical downscaling of rainfall changes in Hawai‘i based on the CMIP5 global model projections
Authors: Timm Oliver Elison , Giambelluca Thomas W. , Diaz Henry F. 
Published: December 2014

AbstractSeasonal mean rainfall projections for Hawai‘i are given based on statistical downscaling of the latest Coupled Model Intercomparison Project phase 5 (CMIP5) global model results for two future representative concentration pathways (RCP4.5 and RCP8.5). The spatial information content of our statistical downscaling method is improved over previous efforts through the inclusion of spatially extensive, high‐quality monthly rainfall data set and the use of improved large‐scale climate predictor information. Predictor variables include moisture transport in the middle atmosphere (700 hPa), vertical temperature gradients, and geopotential height fields of the 1000 and 500 hPa layers. The results allow for the first time to derive a spatially interpolated map with future rainfall change estimates for the main Hawaiian Islands. The statistical downscaling was applied to project wet (November–April) and dry (May–October) season rainfall anomalies for the middle and late 21st century. Overall, the statistical downscaling gives more reliable results for the wet season than for the dry season. The wet‐season results indicate a pronounced dipole structure between windward facing mountain slopes and the leeward side of most of the islands. The climatically wet regions on the windward slopes of the mountain regions are expected to become wetter or remain stable in their seasonal precipitation amounts. On the climatically dry leeward sides of Kaua‘i, O‘ahu, Maui, and Hawai‘i Island, future precipitation exhibits the strongest drying trends. The projected future rainfall anomaly pattern is associated with a circulation anomaly that resembles a shift in the position or strength of the subtropical high and the average location of extratropical troughs. These new results suggest that a negative trend dominates the area‐averaged changes in the statistical downscaling over the Hawaiian Islands. However, the islands are expected to experience a greater contrast between the wet and dry regions in the future.