Preroughening, Diffusion, and Growth of An FCC(111) Surface

Preroughening of close-packed fcc(111) surfaces, found in rare gas solids, is an interesting, but poorly characterized phase transition. We introduce a restricted solid-on-solid model, named FCSOS, which describes it. Using mostly Monte Carlo, we study both statics, including critical behavior and scattering properties, and dynamics, including surface diffusion and growth. In antiphase scattering, it is shown that preroughening will generally show up at most as a dip. Surface growth is predicted to be continuous at preroughening, where surface self-diffusion should also drop. The physical mechanism leading to preroughening on rare gas surfaces is analysed, and identified in the step-step elastic repulsion.Comment: Revtex + uuencoded figures, to appear in Physical Review Letter

A Good Samaritan inspired foundation for a fair health care system

Distributive justice on the income and on the service aspects is the most vexing modern day problem for the creation and maintenance of an all inclusive health care system. A pervasive problem of all current schemes is the lack of effective cost control, which continues to result in increasing burdens for all public and private stakeholders. This proposal posits that the responsibility and financial obligation to achieve an ideal outcome of equal and affordable access and benefits for all citizens is misplaced. The Good Samaritan demonstrated basic ethical principles, which are revisited, elaborated and integrated into a new approach to health care. The participants are limited to individual contributors and beneficiaries and organized as a citizen carried, closed, independent, and self-sufficient self-governing cooperative for their own and the benefit of a minority of disadvantaged health care consumers. The government assumes oversight, provides arbitration, enforces democratic decision making, a scheme of progressive taxation, a separate and transparent accounting system, and a balance between income and reinvestment in health care. The results are a fair distribution of cost, its effective control, and increased individual motivation to take on responsibility for personal health as a private good and a sharpened focus towards community health. At the sociopolitical level the government as well as employers are released from the inappropriate burden of catering to individual health

New life sciences innovation and distributive justice: rawlsian goods versus senian capabilities

The successful decoding of human genome and subsequent advances in new life sciences innovation create technological presuppositions of a new possibility of justice i.e. the just distribution of both social (income, wealth, etc.) and natural (rationality, intelligence, etc.) goods. Although Rawlsians attempt to expand their theory to include this new possibility, they fail to provide plausible metrics of social justice in the genomics and post-genomics era. By contrast, Senians seem to succeed to do so through their index of basic capabilities. This paper explores what might be regarded as a Senian perspective of distributive justice in new life sciences innovation. The argument is that, by comparing freedoms (different functionings) instead of primary goods, the capability theory allows not only for the identification of injustices linked to natural lottery but also for their elimination through the use of new genomic technologies, including gene-based diagnostics, gene therapy, somatic cell engineering (SCE) and germ-line engineering (GLE). These innovative technologies seem to have the potential to reduce variability in natural goods and therefore enable individuals to convert social goods into well-being or welfare

Micro-CT imaging reveals<i> Mekk3 </i>heterozygosity prevents cerebral cavernous malformations in <i>Ccm2</i>-deficient mice

Mutations in CCM1 (aka KRIT1), CCM2, or CCM3 (aka PDCD10) gene cause cerebral cavernous malformation in humans. Mouse models of CCM disease have been established by deleting Ccm genes in postnatal animals. These mouse models provide invaluable tools to investigate molecular mechanism and therapeutic approaches for CCM disease. However, the full value of these animal models is limited by the lack of an accurate and quantitative method to assess lesion burden and progression. In the present study we have established a refined and detailed contrast enhanced X-ray micro-CT method to measure CCM lesion burden in mouse brains. As this study utilized a voxel dimension of 9.5μm (leading to a minimum feature size of approximately 25μm), it is therefore sufficient to measure CCM lesion volume and number globally and accurately, and provide high-resolution 3-D mapping of CCM lesions in mouse brains. Using this method, we found loss of Ccm1 or Ccm2 in neonatal endothelium confers CCM lesions in the mouse hindbrain with similar total volume and number. This quantitative approach also demonstrated a rescue of CCM lesions with simultaneous deletion of one allele of Mekk3. This method would enhance the value of the established mouse models to study the molecular basis and potential therapies for CCM and other cerebrovascular diseases

CO2: An operational anthropogenic CO2 emissions monitoring & verification support capacity

This is the third report form the CO2 Monitoring Task Force on the multiple input streams of in-situ observations that are requirement for the Copernicus CO2 Monitoring and Verification Support capacity to: (i) calibrated and validate the space component, (ii) assimilate data in the models and integrate information in the core of the system, and (iii) evaluate the output generated by the system for its end users. The availability of sustained in situ networks is currently a significant factor of risk that needs to be mitigated to establish a European CO 2 support capacity which is fit-for-purpose. The current status of existing networks may be the source of large uncertainties in anthropogenic CO2 emission estimates as well as limited capability in meeting the requirements for country, large city and point source scale assessments. This conclusion results from a risk analysis formulated for four scenarios: 1) maintaining the status quo, 2) assuring sustained funding for the status quo, 3) enhancing network capabilities at European scale with sustained funding and 4) with a significantly improved in situ infrastructure in Europe and beyond. This report substantiates the multifaceted needs and requirements of the European CO2 support capacity with respect to in situ observations. The analysis concerns all core elements of the envisaged integrated system with a particular attention on the impact of such observations in achieving the proposed objectives. The specific needs for the validation of products delivered by the space component that is, the Copernicus Sentinels CO2 monitoring constellation, are addressed as another prerequisite for the success of the CO2 support capacity. This European asset will represent a significant contribution to the virtual constellation proposed by the Committee on Earth Observation Satellites (CEOS) and, accordingly, complementary requirements are elaborated in that international frame. The report highlights that although high measurement standards are present within existing networks such as ICOS, in the context of the needs for targeted in situ data for the realization of the operational system, these data are not fully fit-for-purpose. A fundamental prerequisite is to have a good geographical coverage over Europe for evaluating the data assimilation and modeling system over a large variety of environmental conditions such as, for instance, urban areas, agricultural regions, forested zones and industrial complexes. The in situ observations need to be extended under a coordinated European lead with sustained infrastructure and targeted additional and maintained long-term funding. It has been clearly understood from the onset that the international dimension of the European CO2 support capacity would be critical and that these aspects should be developed in parallel to, and in synergy with the definition and implementation of a European contributing system. It was also understood that this international dimension had both strategic, policy relevant and technical dimensions and the Commission and the relevant European institutional partners have started since several years to engage both bilaterally and multilaterally with the relevant stakeholders and counterparts to develop these relations. Specifically, CEOS will undertake, over the next few years, dedicated preparatory work in a coordinated international context, to provide cumulative added value to the specific programmatic activities of their member agencies. Concerted efforts have already begun in the context of the European Commission's Chairmanship of CEOS in 2018. It is recognized in the context of the European efforts, and increasingly by our international counterparts that a broad and holistic system approach is required to address the requirements which are represented by the climate policy, of which the satellite component, whilst important, cannot effectively be developed in isolation. This system indeed includes the satellite observing capability but in addition, the required modelling component and data integration elements, prior information, ancillary data and in situ observations delivered by essential networks. Acknowledging the need for an efficient coordination at international level for instance via the Global Atmosphere Watch programme of the World Meteorological Organisation is a key towards a successful implementation of appropriate actions to ensure the sustainability of essential networks, to enhance current network capabilities with new observations and to propose adequate governance schemes. Such actions to mitigate current network limitations are deemed critical to implementing the Copernicus CO 2 Monitoring & Verification Support capacity in its full strength.JRC.D.6-Knowledge for Sustainable Development and Food Securit

Defining the Functional Domain of Programmed Cell Death 10 through Its Interactions with Phosphatidylinositol-3,4,5-Trisphosphate

Cerebral cavernous malformations (CCM) are vascular abnormalities of the central nervous system predisposing blood vessels to leakage, leading to hemorrhagic stroke. Three genes, Krit1 (CCM1), OSM (CCM2), and PDCD10 (CCM3) are involved in CCM development. PDCD10 binds specifically to PtdIns(3,4,5)P3 and OSM. Using threading analysis and multi-template modeling, we constructed a three-dimensional model of PDCD10. PDCD10 appears to be a six-helical-bundle protein formed by two heptad-repeat-hairpin structures (α1–3 and α4–6) sharing the closest 3D homology with the bacterial phosphate transporter, PhoU. We identified a stretch of five lysines forming an amphipathic helix, a potential PtdIns(3,4,5)P3 binding site, in the α5 helix. We generated a recombinant wild-type (WT) and three PDCD10 mutants that have two (Δ2KA), three (Δ3KA), and five (Δ5KA) K to A mutations. Δ2KA and Δ3KA mutants hypothetically lack binding residues to PtdIns(3,4,5)P3 at the beginning and the end of predicted helix, while Δ5KA completely lacks all predicted binding residues. The WT, Δ2KA, and Δ3KA mutants maintain their binding to PtdIns(3,4,5)P3. Only the Δ5KA abolishes binding to PtdIns(3,4,5)P3. Both Δ5KA and WT show similar secondary and tertiary structures; however, Δ5KA does not bind to OSM. When WT and Δ5KA are co-expressed with membrane-bound constitutively-active PI3 kinase (p110-CAAX), the majority of the WT is co-localized with p110-CAAX at the plasma membrane where PtdIns(3,4,5)P3 is presumably abundant. In contrast, the Δ5KA remains in the cytoplasm and is not present in the plasma membrane. Combining computational modeling and biological data, we propose that the CCM protein complex functions in the PI3K signaling pathway through the interaction between PDCD10 and PtdIns(3,4,5)P3

Evaluation of receptor and chemical transport models for PM10 source apportionment

In this study, the performance of two types of source apportionment models was evaluated by assessing the results provided by 40 different groups in the framework of an intercomparison organised by FAIRMODE WG3 (Forum for air quality modelling in Europe, Working Group 3). The evaluation was based on two performance indicators: z-scores and the root mean square error weighted by the reference uncertainty (RMSEu), with pre-established acceptability criteria. By involving models based on completely different and independent input data, such as receptor models (RMs) and chemical transport models (CTMs), the intercomparison provided a unique opportunity for their cross-validation. In addition, comparing the CTM chemical profiles with those measured directly at the source contributed to corroborate the consistency of the tested model results. The most commonly used RM was the US EPA- PMF version 5. RMs showed very good performance for the overall dataset (91% of z-scores accepted) while more difficulties were observed with the source contribution time series (72% of RMSEu accepted). Industrial activities proved to be the most difficult sources to be quantified by RMs, with high variability in the estimated contributions. In the CTMs, the sum of computed source contributions was lower than the measured gravimetric PM10 mass concentrations. The performance tests pointed out the differences between the two CTM approaches used for source apportionment in this study: brute force (or emission reduction impact) and tagged species methods. The sources meeting the z-score and RMSEu acceptability criteria tests were 50% and 86%, respectively. The CTM source contributions to PM10 were in the majority of cases lower than the RM averages for the corresponding source. The CTMs and RMs source contributions for the overall dataset were more comparable (83% of the z-scores accepted) than their time series (successful RMSEu in the range 25% - 34%). The comparability between CTMs and RMs varied depending on the source: traffic/exhaust and industry were the source categories with the best results in the RMSEu tests while the most critical ones were soil dust and road dust. The differences between RMs and CTMs source reconstructions confirmed the importance of cross validating the results of these two families of models

KRIT1 Regulates the Homeostasis of Intracellular Reactive Oxygen Species

KRIT1 is a gene responsible for Cerebral Cavernous Malformations (CCM), a major cerebrovascular disease characterized by abnormally enlarged and leaky capillaries that predispose to seizures, focal neurological deficits, and fatal intracerebral hemorrhage. Comprehensive analysis of the KRIT1 gene in CCM patients has suggested that KRIT1 functions need to be severely impaired for pathogenesis. However, the molecular and cellular functions of KRIT1 as well as CCM pathogenesis mechanisms are still research challenges. We found that KRIT1 plays an important role in molecular mechanisms involved in the maintenance of the intracellular Reactive Oxygen Species (ROS) homeostasis to prevent oxidative cellular damage. In particular, we demonstrate that KRIT1 loss/down-regulation is associated with a significant increase in intracellular ROS levels. Conversely, ROS levels in KRIT1−/− cells are significantly and dose-dependently reduced after restoration of KRIT1 expression. Moreover, we show that the modulation of intracellular ROS levels by KRIT1 loss/restoration is strictly correlated with the modulation of the expression of the antioxidant protein SOD2 as well as of the transcriptional factor FoxO1, a master regulator of cell responses to oxidative stress and a modulator of SOD2 levels. Furthermore, we show that the KRIT1-dependent maintenance of low ROS levels facilitates the downregulation of cyclin D1 expression required for cell transition from proliferative growth to quiescence. Finally, we demonstrate that the enhanced ROS levels in KRIT1−/− cells are associated with an increased cell susceptibility to oxidative DNA damage and a marked induction of the DNA damage sensor and repair gene Gadd45α, as well as with a decline of mitochondrial energy metabolism. Taken together, our results point to a new model where KRIT1 limits the accumulation of intracellular oxidants and prevents oxidative stress-mediated cellular dysfunction and DNA damage by enhancing the cell capacity to scavenge intracellular ROS through an antioxidant pathway involving FoxO1 and SOD2, thus providing novel and useful insights into the understanding of KRIT1 molecular and cellular functions