The transition to sustainable mobility is critical to the world. Dealing with the transition is difficult because people holding distinct worldviews may vary in environmental attitudes and travel ...patterns. However, current mobility choice models fail to consider diverse worldviews. This would limit their use for addressing complex, debated issues such as the mode switch from private car to public transport. This research attempts to incorporate worldviews into the study of sustainable mobility transitions. Three cultures or worldviews defined by Cultural Theory are utilised. Egalitarianism highlights social equity and environmental rights. Hierarchy values order and conformity. Individualism endorses individual autonomy and economic growth. They represent three rationalities about social life and sustainability. In this research, a behavioural and decision making framework that can capture the influence of worldviews on mobility choices is proposed. The framework is implemented by an agent-based model, the London Mobility Model, to explore the transition from private car to public transport in London. This model requires the outputs of two models. First, the British Worldviews Model measures worldviews in Great Britain and groups British people into three types of worldview adherents. It shows that on average, egalitarians have the highest environmental awareness of car use problems; hierarchists, have the medium; and individualists, have the lowest. Second, a spatial microsimulation model, the London Worldviews Model, estimates worldviews across space and populations in London. The model produces a synthetic population that allocates Londoners to this city, illustrating distinct residential patterns of the three worldview groups. Built on these results, the London Mobility Model views London as a complex system. It portrays Londoners as the three types of adherents, who vary in population and contextual characteristics. The results identify distinct transition pathways to sustainability, demonstrating that worldviews have the potential to link various aspects of sustainable mobility and urban complexities.
It is well known that spatial and temporal regulation of genes is an integral part of governing proper gene expression. Consequently, it is invaluable to understand where and when transcription is ...taking place within nuclear space and to visualize the relationship between episomes infected within the same cell's nucleus. Here, both immunofluorescence (IFA) and RNA-FISH have been combinedto identify actively transcribing Kaposi's sarcoma-associated herpesvirus (KSHV) episomes. By staining KSHV latency-associated nuclear antigen (LANA), it is possible to locate where viral episomes exist within the nucleus. In addition, by designing RNA-FISH probes to target the intron region of a viral gene, which is expressed only during productive infection, nascent RNA transcripts can be located. Using this combination of molecular probes, it is possible to visualize the assembly of large viral transcription factories and analyze the spatial regulation of viral gene expression during KSHV reactivation. By including anti-RNA polymerase II antibody staining, one can also visualize the association between RNA polymerase II (RNAPII) aggregation and KSHV transcription during reactivation.
Abstract
Lunar swirls are recognized as broad, bright albedo features in various regions of the Moon. These features are often separated by dark off-swirl lanes or terminate against the dark ...background, such as lunar maria. Prior mapping of swirls has been done primarily by albedo contrast, which is prone to subjectivity. Closer examination of on-swirl areas shows that they are not uniform, making the boundary between on- and off-swirl difficult to map with certainty. We have applied machine learning techniques to address these issues by identifying the number of swirl units and then mapping them based on actual reflectance, or I/F data. Using LROC NAC paired stereo images that are converted to I/F reflectance at a range of incidence angles, we applied both unsupervised K-means clustering and supervised Maximum Likelihood Classification algorithms to classify and map portions of lunar swirls in Reiner Gamma and Mare Ingenii. Results show that the classification maps are a reasonable match to the representative albedos for the two study regions. A third transitionary swirl unit, termed diffuse-swirl, is present in both the maps and the cumulative distribution plots of the reflectance values. Overall, we find that the use of both algorithms provides independent confirmation of both the number and location of these units and their interrelation. More importantly, the algorithms remove mapping subjectivity by using quantitative information. The data and the statistics generated from the maps also have value in future studies by placing limits for categorizing swirl units in different regions on the Moon.
Abstract
The overall cure rate of primary tumors has been significantly improved in the last three decades; however, metastatic and recurrent tumors with aggressive growth and therapy-resistance ...remain as the major factors shortening breast cancer patients’ survival. MKP1, a mitogen-activated protein kinase (MAPK) phosphatase, was shown to be linked with chemoresistance in breast cancer cells and was over-expressed in radio-resistant breast cancer cells that survived long-term fractionated irradiation. Herein, we showed that MKP1 is expressed exclusively in HER2 positive clinical breast tumors compared to HER2 negative tumors. Comparison of normal and tumor breast tissue samples from same patients revealed that MKP1 expression is induced in breast tumors along with HER2 expression in patients, who showed low/no expression of MKP1 and HER2 in their normal breast tissue. Most importantly, we have shown that HER2 positive breast cancer cells rely heavily on MKP1 for survival as knocking down MKP1 resulted in a massive cell death. MKP1 was found to translocate into the mitochondria in breast cancer cells upon radiation and mitochondrial MKP1 levels were significantly enhanced in HER2 over-expressing and radio-resistant breast cancer cells, suggesting a survival mechanism where increased MKP1 translocation into the mitochondria functions to attenuate pro-apoptotic signals initiated from mitochondria-localized MAPK, c-Jun N-terminal kinase (JNK). Consistent with this, increased mitochondrial MKP1 levels were correlated with the reduced levels of phosphorylated active JNK in the mitochondria of irradiated cells. Such mitochondrial MKP1-mediated dephosphorylation of JNK was predominantly enhanced in the radio-resistant breast cancer cells that can be sensitized by siRNA-mediated inhibition of MKP1. The identification of cancer stem cells (CSCs) in all human tumors and their involvement in tumor radioresistance encouraged the studies investigating whether MKP1-mediated survival mechanism is present in radio-resistant breast cancer stem cells. Here, we showed that MKP1 is overexpressed in irradiated HER2-positive breast CSCs (HER2+/CD44+/CD24-/low) and knocking down MKP1 in these cells significantly reduced their survival, which was further reduced with radiation treatment. These data provide critical insights on the aggressive phenotype of breast tumors and offer MKP1 as a novel diagnostic and therapeutic target to re-sensitize resistant breast cancer stem cells. Identification of the mechanism of MKP1-mediated survival in these cells may provide additional druggable targets to control breast cancer and its recurrence.
Citation Format: Demet Candas, Chung-Ling Lu, Ming Fan, Frank Chuang, Colleen Sweeney, Alexander Borowsky, Jian Jian Li. MKP1-mediated survival of HER2 positive breast cancer stem cells. abstract. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3029. doi:10.1158/1538-7445.AM2014-3029
The High Resolution Imaging Science Experiment (HiRISE) on the Mars Reconnaissance Orbiter (MRO) acquired 8
terapixels of data in 9137 images of Mars between October 2006 and December 2008, covering ...∼0.55% of the surface. Images are typically 5–6
km wide with 3-color coverage over the central 20% of the swath, and their scales usually range from 25 to 60
cm/pixel. Nine hundred and sixty stereo pairs were acquired and more than 50 digital terrain models (DTMs) completed; these data have led to some of the most significant science results. New methods to measure and correct distortions due to pointing jitter facilitate topographic and change-detection studies at sub-meter scales. Recent results address Noachian bedrock stratigraphy, fluvially deposited fans in craters and in or near Valles Marineris, groundwater flow in fractures and porous media, quasi-periodic layering in polar and non-polar deposits, tectonic history of west Candor Chasma, geometry of clay-rich deposits near and within Mawrth Vallis, dynamics of flood lavas in the Cerberus Palus region, evidence for pyroclastic deposits, columnar jointing in lava flows, recent collapse pits, evidence for water in well-preserved impact craters, newly discovered large rayed craters, and glacial and periglacial processes. Of particular interest are ongoing processes such as those driven by the wind, impact cratering, avalanches of dust and/or frost, relatively bright deposits on steep gullied slopes, and the dynamic seasonal processes over polar regions. HiRISE has acquired hundreds of large images of past, present and potential future landing sites and has contributed to scientific and engineering studies of those sites. Warming the focal-plane electronics prior to imaging has mitigated an instrument anomaly that produces bad data under cold operating conditions.
HiRISE images of Mars with ground sampling down to 25
cm/pixel show that the dust-rich mantle covering the surfaces of the Tharsis Montes is organized into ridges whose form and distribution are ...consistent with formation by aeolian saltation. Other dusty areas near the volcanoes and elsewhere on the planet exhibit a similar morphology. The material composing these “reticulate” bedforms is constrained by their remote sensing properties and the threshold curve combined with the saltation/suspension boundary, both of which vary as a function of elevation (atmospheric pressure), particle size, and particle composition. Considering all of these factors, dust aggregates are the most likely material composing these bedforms. We propose that airfall dust on and near the volcanoes aggregates
in situ over time, maybe due to electrostatic charging followed by cementation by salts. The aggregates eventually reach a particle size at which saltation is possible. Aggregates on the flanks are transported downslope by katabatic winds and form linear and “accordion” morphologies. Materials within the calderas and other depressions remain trapped and are subjected to multidirectional winds, forming an interlinked “honeycomb” texture. In many places on and near the volcanoes, light-toned, low thermal inertia yardangs and indurated surfaces are present. These may represent “duststone” formed when aggregates reach a particle size below the threshold curve, such that they become stabilized and subsequently undergo cementation.
Abstract
The overall cure rate of primary tumors has been significantly improved in the last three decades; however, metastatic and recurrent tumors with aggressive growth and therapy-resistance ...remain as the major factors shortening breast cancer patients’ survival. MKP1, a mitogen-activated protein kinase (MAPK) phosphatase, was shown to be linked with chemoresistance in breast cancer cells and was overexpressed in radioresistant breast cancer cells that survived long-term fractionated irradiation. Herein, we showed that MKP1 is present in the mitochondria and mitochondrial MKP1 levels are significantly enhanced in irradiated cells, suggesting that increased MKP1 translocation into the mitochondria may function to attenuate pro-apoptotic signals that were initiated from mitochondria-localized MAPK, c-Jun N-terminal kinase (JNK). We found that increased mitochondrial MKP1 levels correlated with the reduced level of phosphorylated active JNK in irradiated cells. Such mitochondrial MKP1-mediated dephosphorylation of JNK was predominantly enhanced in the radioresistant breast cancer cells that can be sensitized by siRNA-mediated inhibition of MKP1. Our results also demonstrated the involvement of extracellular regulated kinase (ERK) as the upstream signal for MKP1 mitochondrial translocation. The identification of cancer stem cells (CSCs) in all human tumors and their involvement in tumor radioresistance encouraged the studies investigating whether MKP1-mediated survival mechanism is present in radioresistant breast cancer cells. Here we showed that MKP1 is overexpressed in irradiated HER2-positive breast CSCs. These data provide critical insights on the aggressive phenotype of breast tumors and define novel diagnostic and therapeutic targets to re-sensitize resistant breast cancer stem cells.
Citation Format: Demet Candas, Frank Chuang, Ming Fan, Rulong Shen, Colleen Sweeney, Alexander Borowsky, Andrew Vaughan, Jian Jian Li. Mitochondrial MKP1-mediated radioresistance in breast cancer stem cells. abstract. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 74. doi:10.1158/1538-7445.AM2013-74
A Late Noachian-aged alluvial fan complex within Harris Crater in far western Terra Tyrrhena, Mars, is comprised of two well-defined source regions and associated discrete depositional lobes. Three ...fan units were recognized based on common morphological characteristics, thermal properties and spectral signatures. Although the entire fan complex has been subjected to extensive erosional degradation, the preserved morphologies record episodic fan formation and indicate the type of flow processes that occurred; the bulk of the fan surface has morphology consistent with fluvial emplacement while one fan unit exhibits a rugged surface texture with boulders consistent with a debris flow. This transition from fluvial to late-stage debris flow(s) suggests a decline in available water and/or change in sediment supply. The thermal inertia values obtained for all three fan surface units (mean values ranged from 318 to 344
J
m
−2
K
−1
s
−1/2) are typical for coarse-grained and/or well-indurated materials on Mars, but subtle variations point to important distinctions. Variations in aeolian bedform coverage as well as the density of ridges (inferred inverted channels) and boulders contribute to these subtle fan thermophysical differences and likely reflect changes in the fan depositional mechanisms and variations in post-depositional modification histories. The majority of the alluvial fan surface has a spectral signature that is broadly similar to TES “Surface Type 2” (ST2), with some important exceptions at long wavelengths. However, a unique spectral component was identified in one of the fan units (unit 3), that likely reflects lithological differences from other fan materials. This spectral attribute of unit 3 matched locations within the western catchment providing confirmation of provenance and supporting the contention that sediment supply changed over time as the fan developed. Finally, we applied simple modeling to a well preserved subsection of the fan complex to quantify the developmental history. Using the computed eastern fan volume (32
km
3), significant water, likely from precipitation, was involved in fan construction (>50
km
3) and an extensive period of fan formation occurred over millennia or longer.
HIV causes rapid CD4+ T cell depletion in the gut mucosa, resulting in immune deficiency and defects in the intestinal epithelial barrier. Breakdown in gut barrier integrity is linked to chronic ...inflammation and disease progression. However, the early effects of HIV on the gut epithelium, prior to the CD4+ T cell depletion, are not known. Further, the impact of early viral infection on mucosal responses to pathogenic and commensal microbes has not been investigated. We utilized the SIV model of AIDS to assess the earliest host-virus interactions and mechanisms of inflammation and dysfunction in the gut, prior to CD4+ T cell depletion. An intestinal loop model was used to interrogate the effects of SIV infection on gut mucosal immune sensing and response to pathogens and commensal bacteria in vivo. At 2.5 days post-SIV infection, low viral loads were detected in peripheral blood and gut mucosa without CD4+ T cell loss. However, immunohistological analysis revealed the disruption of the gut epithelium manifested by decreased expression and mislocalization of tight junction proteins. Correlating with epithelial disruption was a significant induction of IL-1β expression by Paneth cells, which were in close proximity to SIV-infected cells in the intestinal crypts. The IL-1β response preceded the induction of the antiviral interferon response. Despite the disruption of the gut epithelium, no aberrant responses to pathogenic or commensal bacteria were observed. In fact, inoculation of commensal Lactobacillus plantarum in intestinal loops led to rapid anti-inflammatory response and epithelial tight junction repair in SIV infected macaques. Thus, intestinal Paneth cells are the earliest responders to viral infection and induce gut inflammation through IL-1β signaling. Reversal of the IL-1β induced gut epithelial damage by Lactobacillus plantarum suggests synergistic host-commensal interactions during early viral infection and identify these mechanisms as potential targets for therapeutic intervention.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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