157 research outputs found
The geological history of Nili Patera, Mars
Nili Patera is a 50âkm diameter caldera at the center of the Syrtis Major Planum volcanic province. The caldera is unique among Martian volcanic terrains in hosting: (i) evidence of both effusive and explosive volcanism, (ii) hydrothermal silica, and (iii) compositional diversity from olivine-rich basalts to silica-enriched units. We have produced a new geological map using three mosaicked 18âm/pixel Context Camera digital elevation models, supplemented by Compact Remote Imaging Spectrometer for Mars Hyperspectral data. The map contextualizes these discoveries, formulating a stratigraphy in which Nili Patera formed by trapdoor collapse into a volcanotectonic depression. The distinctive bright floor of Nili Patera formed either as part of a felsic pluton, exposed during caldera formation, or as remnants of welded ignimbrite(s) associated with caldera formationâboth scenarios deriving from melting in the Noachian highland basement. After caldera collapse, there were five magmatic episodes: (1) a basaltic unit in the caldera's north, (2) a silica-enriched unit and the associated Nili Tholus cone, (3) an intrusive event, forming a ~300âm high elliptical dome; (4) an extrusive basaltic unit, emplaced from small cones in the east; and (5) an extreme olivine-bearing unit, formed on the western caldera ring fault. The mapping, together with evidence for hydrated materials, implies magmatic interaction with subsurface volatiles. This, in an area of elevated geothermal gradient, presents a possible habitable environment (sampled by the hydrothermal deposits). Additionally, similarities to other highland volcanoes imply similar mechanisms and thus astrobiological potential within those edifices
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Preliminary site report for the 2005 ICDP-USGS deep corehole in the Chesapeake Bay impact crater
First report for the ICDP-USGS 1.7-km-deep corehole drilled into the central part of the Chesapeake Bay impact crater during 2005
Discussing Uncertainty and Risk in Primary Care: Recommendations of a Multi-Disciplinary Panel Regarding Communication Around Prostate Cancer Screening
BACKGROUND: Shared decision making improves value-concordant decision-making around prostate cancer screening (PrCS). Yet, PrCS discussions remain complex, challenging and often emotional for physicians and average-risk men. OBJECTIVE: In July 2011, the Centers for Disease Control and Prevention convened a multidisciplinary expert panel to identify priorities for funding agencies and development groups to promote evidence-based, value-concordant decisions between men at average risk for prostate cancer and their physicians. DESIGN: Two-day multidisciplinary expert panel in Atlanta, Georgia, with structured discussions and formal consensus processes. PARTICIPANTS: Sixteen panelists represented diverse specialties (primary care, medical oncology, urology), disciplines (sociology, communication, medical education, clinical epidemiology) and market sectors (patient advocacy groups, Federal funding agencies, guideline-development organizations). MAIN MEASURES: Panelists used guiding interactional and evaluation models to identify and rate strategies that might improve PrCS discussions and decisions for physicians, patients and health systems/society. Efficacy was defined as the likelihood of each strategy to impact outcomes. Effort was defined as the relative amount of effort to develop, implement and sustain the strategy. Each strategy was rated (1â7 scale; 7 = maximum) using group process software (ThinkTank(TM)). For each group, intervention strategies were grouped as financial/regulatory, educational, communication or attitudinal levers. For each strategy, barriers were identified. KEY RESULTS: Highly ranked strategies to improve value-concordant shared decision-making (SDM) included: changing outpatient clinic visit reimbursement to reward SDM; development of evidence-based, technology-assisted, point-of-service tools for physicians and patients; reframing confusing prostate cancer screening messages; providing pre-visit decision support interventions; utilizing electronic health records to promote benchmarking/best practices; providing additional training for physicians around value-concordant decision-making; and using re-accreditation to promote training. CONCLUSIONS: Conference outcomes present an expert consensus of strategies likely to improve value-concordant prostate cancer screening decisions. In addition, the methodology used to obtain agreement provides a model of successful collaboration around this and future controversial cancer screening issues, which may be of interest to funding agencies, educators and policy makers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11606-013-2419-z) contains supplementary material, which is available to authorized users
Inhibitors of apoptosis proteins in human cervical cancer
BACKGROUND: It has been shown that IAPs, in particular XIAP, survivin and c-IAP1, are overexpressed in several malignancies. In the present study we investigate the expression of c-IAP1, c-IAP2, XIAP and survivin and its isoforms in cervical cancer. METHODS: We used semiquantitative RT-PCR assays to analyze 41 cancer and 6 normal tissues. The study included 8 stage I cases; 16 stage II; 17 stageIII; and a control group of 6 samples of normal cervical squamous epithelial tissue. RESULTS: c-IAP2 and XIAP mRNA levels were similar among the samples, cervical tumors had lower c-IAP1 mRNA levels. Unexpectedly, a clear positive association was found between low levels of XIAP and disease relapse. A log-rank test showed a significant inverse association (p = 0.02) between XIAP expression and tumor aggressiveness, as indicated by disease relapse rates. There were no statistically significant differences in the presence or expression levels of c-IAP1 and c-IAP2 among any of the clinical variables studied. Survivin and its isoforms were undetectable in normal cervical tissues, in contrast with the clear upregulation observed in cancer samples. We found no association between survivin expression and age, clinical stage, histology or menopausal state. Nevertheless, we found that adenocarcinoma tumors expressed higher levels of survivin 2B and DeltaEx3 (p = 0.001 and p = 0.04 respectively, by Kruskal-Wallis). A multivariate Cox's partial likelihood-based analysis showed that only FIGO stage was an independent predictor of outcome. CONCLUSION: There are no differences in the expression of c-IAP2 and XIAP between normal vs. cancer samples, but XIAP expression correlate in cervical cancer with relapse of this disease in the patients. Otherwise, c-IAP1 was downregulated in the cervical cancer samples. The expression of survivin was upregulated in the patients with cervical cancer. We have found that adenocarcinoma presented higher levels of survivin isoforms 2B and DeltaEx3
Assessing the context of health care utilization in Ecuador: A spatial and multilevel analysis
<p>Abstract</p> <p>Background</p> <p>There are few studies that have analyzed the context of health care utilization, particularly in Latin America. This study examines the context of utilization of health services in Ecuador; focusing on the relationship between provision of services and use of both preventive and curative services.</p> <p>Methods</p> <p>This study is cross-sectional and analyzes data from the 2004 National Demographic and Maternal & Child Health dataset. Provider variables come from the Ecuadorian System of Social Indicators (SIISE). Global Moran's I statistic is used to assess spatial autocorrelation of the provider variables. Multilevel modeling is used for the simultaneous analysis of provision of services at the province-level with use of services at the individual level.</p> <p>Results</p> <p>Spatial analysis indicates no significant differences in the density of health care providers among Ecuadorian provinces. After adjusting for various predisposing, enabling, need factors and interaction terms, density of public practice health personnel was positively associated with use of preventive care, particularly among rural households. On the other hand, density of private practice physicians was positively associated with use of curative care, particularly among urban households.</p> <p>Conclusions</p> <p>There are significant public/private, urban/rural gaps in provision of services in Ecuador; which in turn affect people's use of services. It is necessary to strengthen the public health care delivery system (which includes addressing distribution of health workers) and national health information systems. These efforts could improve access to health care, and inform the civil society and policymakers on the advances of health care reform.</p
Corresponding Functional Dynamics across the Hsp90 Chaperone Family: Insights from a Multiscale Analysis of MD Simulations
Understanding how local protein modifications, such as binding small-molecule ligands, can trigger and regulate large-scale motions of large protein domains is a major open issue in molecular biology. We address various aspects of this problem by analyzing and comparing atomistic simulations of Hsp90 family representatives for which crystal structures of the full length protein are available: mammalian Grp94, yeast Hsp90 and E.coli HtpG. These chaperones are studied in complex with the natural ligands ATP, ADP and in the Apo state. Common key aspects of their functional dynamics are elucidated with a novel multi-scale comparison of their internal dynamics. Starting from the atomic resolution investigation of internal fluctuations and geometric strain patterns, a novel analysis of domain dynamics is developed. The results reveal that the ligand-dependent structural modulations mostly consist of relative rigid-like movements of a limited number of quasi-rigid domains, shared by the three proteins. Two common primary hinges for such movements are identified. The first hinge, whose functional role has been demonstrated by several experimental approaches, is located at the boundary between the N-terminal and Middle-domains. The second hinge is located at the end of a three-helix bundle in the Middle-domain and unfolds/unpacks going from the ATP- to the ADP-state. This latter site could represent a promising novel druggable allosteric site common to all chaperones
Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential
The tumour microenvironment is believed to be involved in development, growth, metastasis, and therapy resistance of many cancers. Here we show survivin, a member of the inhibitor of apoptosis protein (IAP) family, implicated in apoptosis inhibition and the regulation of mitosis in cancer cells, exists in a novel extracellular pool in tumour cells. Furthermore, we have constructed stable cell lines that provide the extracellular pool with either wild-type survivin (Surv-WT) or the previously described dominant-negative mutant survivin (Surv-T34A), which has proven pro-apoptotic effects in cancer cells but not in normal proliferating cells. Cancer cells grown in conditioned medium (CM) taken from Surv-WT cells absorbed survivin and experienced enhanced protection against genotoxic stresses. These cells also exhibited an increased replicative and metastatic potential, suggesting that survivin in the tumour microenvironment may be directly associated with malignant progression, further supporting survivin's function in tumourigenesis. Alternatively, cancer cells grown in CM taken from the Surv-T34A cells began to apoptose through a caspase-2- and caspase-9-dependent pathway that was further enhanced by the addition of other chemo- and radiotherapeutic modalities. Together our findings suggest a novel microenvironmental function for survivin in the control of cancer aggressiveness and spread, and should result in the genesis of additional cancer treatment modalities
The dynamic geophysical environment of (101955) Bennu based on OSIRIS-REx measurements
The top-shaped morphology characteristic of asteroid (101955) Bennu, often found among fast-spinning asteroids and binary asteroid primaries, may have contributed substantially to binary asteroid formation. Yet a detailed geophysical analysis of this morphology for a fast-spinning asteroid has not been possible prior to the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission. Combining the measured Bennu mass and shape obtained during the Preliminary Survey phase of the OSIRIS-REx mission, we find a notable transition in Bennuâs surface slopes within its rotational Roche lobe, defined as the region where material is energetically trapped to the surface. As the intersection of the rotational Roche lobe with Bennuâs surface has been most recently migrating towards its equator (given Bennuâs increasing spin rate), we infer that Bennuâs surface slopes have been changing across its surface within the last million years. We also find evidence for substantial density heterogeneity within this body, suggesting that its interior is a mixture of voids and boulders. The presence of such heterogeneity and Bennuâs top shape are consistent with spin-induced failure at some point in its past, although the manner of its failure cannot yet be determined. Future measurements by the OSIRIS-REx spacecraft will provide insight into and may resolve questions regarding the formation and evolution of Bennuâs top-shape morphology and its link to the formation of binary asteroids
Evidence for widespread hydrated minerals on asteroid (101955) Bennu
Early spectral data from the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission reveal evidence for abundant hydrated minerals on the surface of near-Earth asteroid (101955) Bennu in the form of a near-infrared absorption near 2.7â”m and thermal infrared spectral features that are most similar to those of aqueously altered CM-type carbonaceous chondrites. We observe these spectral features across the surface of Bennu, and there is no evidence of substantial rotational variability at the spatial scales of tens to hundreds of metres observed to date. In the visible and near-infrared (0.4 to 2.4â”m) Bennuâs spectrum appears featureless and with a blue (negative) slope, confirming previous ground-based observations. Bennu may represent a class of objects that could have brought volatiles and organic chemistry to Earth
Cassini Radio Science
Cassini radio science investigations will be conducted both during the cruise (gravitational wave and conjunction experiments) and the Saturnian tour of the mission (atmospheric and ionospheric occultations, ring occultations, determinations of masses and gravity fields). New technologies in the construction of the instrument, which consists of a portion on-board the spacecraft and another portion on the ground, including the use of the Ka-band signal in addition to that of the S- and X-bands, open opportunities for important discoveries in each of the above scientific areas, due to increased accuracy, resolution, sensitivity, and dynamic range.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43765/1/11214_2004_Article_1436.pd
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