Computer modeling of large asteroid impacts into continental and oceanic sites: Atmospheric, cratering, and ejecta dynamics

Numerous impact cratering events have occurred on the Earth during the last several billion years that have seriously affected our planet and its atmosphere. The largest cratering events, which were caused by asteroids and comets with kinetic energies equivalent to tens of millions of megatons of TNT, have distributed substantial quantities of terrestrial and extraterrestrial material over much or all of the Earth. In order to study a large-scale impact event in detail, computer simulations were completed that model the passage of a 10 km-diameter asteroid through the Earth's atmosphere and the subsequent cratering and ejecta dynamics associated with impact of the asteroid into two different targets, i.e., an oceanic site and a continental site. The calcuations were designed to broadly represent giant impact events that have occurred on the Earth since its formation and specifically represent an impact cratering event proposed to have occurred at the end of Cretaceous time. Calculation of the passage of the asteroid through a U.S. Standard Atmosphere showed development of a strong bow shock that expanded radially outward. Behind the shock front was a region of highly shock compressed and intensely heated air. Behind the asteroid, rapid expansion of this shocked air created a large region of very low density that also expanded away from the impact area. Calculations of the cratering events in both the continental and oceanic targets were carried to 120 s. Despite geologic differences, impacts in both targets developed comparable dynamic flow fields, and by approx. 29 s similar-sized transient craters approx. 39 km deep and approx. 62 km across had formed. For all practical purposes, the atmosphere was nearly completely removed from the impact area for tens of seconds, i.e., air pressures were less than fractions of a bar out to ranges of over 50 km. Consequently, much of the asteroid and target materials were ejected upward into a near vacuum. Effects of secondary volcanism and return of the ocean over hot oceanic crater floor could also be expected to add substantial solid and vaporized material to the atmosphere, but these conditions were not studied

Computer simulations of 10-km-diameter asteroid impacts into oceanic and continental sites: Preliminary results on atmospheric passage, cratering and ejecta dynamics

A series of analytical calculations of large scale cratering events for both oceanic and continental sites were made in order to examine their effects on the target media and atmosphere. The first analytical studies that were completed consists of computer simulations of the dynamics of: (1) the passage of a 10 km diameter asteroid moving at 20 km/sec through the Earth's atmosphere, and (2) the impact cratering events in both oceanic and continental environments. Calculation of the dynamics associated with the passage of the asteroid through the atmosphere showed strong effects on the surrounding air mass. The calculations of the impact cratering events showed equally dramatic effects on the oceanic and continental environments. These effects are briefly discussed

Validation of Statistical Sampling Algorithms in Visual Sample Plan (VSP): Summary Report

The U.S. Department of Homeland Security, Office of Technology Development (OTD) contracted with a set of U.S. Department of Energy national laboratories, including the Pacific Northwest National Laboratory (PNNL), to write a Remediation Guidance for Major Airports After a Chemical Attack. The report identifies key activities and issues that should be considered by a typical major airport following an incident involving release of a toxic chemical agent. Four experimental tasks were identified that would require further research in order to supplement the Remediation Guidance. One of the tasks, Task 4, OTD Chemical Remediation Statistical Sampling Design Validation, dealt with statistical sampling algorithm validation. This report documents the results of the sampling design validation conducted for Task 4. In 2005, the Government Accountability Office (GAO) performed a review of the past U.S. responses to Anthrax terrorist cases. Part of the motivation for this PNNL report was a major GAO finding that there was a lack of validated sampling strategies in the U.S. response to Anthrax cases. The report (GAO 2005) recommended that probability-based methods be used for sampling design in order to address confidence in the results, particularly when all sample results showed no remaining contamination. The GAO also expressed a desire that the methods be validated, which is the main purpose of this PNNL report. The objective of this study was to validate probability-based statistical sampling designs and the algorithms pertinent to within-building sampling that allow the user to prescribe or evaluate confidence levels of conclusions based on data collected as guided by the statistical sampling designs. Specifically, the designs found in the Visual Sample Plan (VSP) software were evaluated. VSP was used to calculate the number of samples and the sample location for a variety of sampling plans applied to an actual release site. Most of the sampling designs validated are probability based, meaning samples are located randomly (or on a randomly placed grid) so no bias enters into the placement of samples, and the number of samples is calculated such that IF the amount and spatial extent of contamination exceeds levels of concern, at least one of the samples would be taken from a contaminated area, at least X% of the time. Hence, "validation" of the statistical sampling algorithms is defined herein to mean ensuring that the "X%" (confidence) is actually met

The composition of the protosolar disk and the formation conditions for comets

Conditions in the protosolar nebula have left their mark in the composition of cometary volatiles, thought to be some of the most pristine material in the solar system. Cometary compositions represent the end point of processing that began in the parent molecular cloud core and continued through the collapse of that core to form the protosun and the solar nebula, and finally during the evolution of the solar nebula itself as the cometary bodies were accreting. Disentangling the effects of the various epochs on the final composition of a comet is complicated. But comets are not the only source of information about the solar nebula. Protostellar disks around young stars similar to the protosun provide a way of investigating the evolution of disks similar to the solar nebula while they are in the process of evolving to form their own solar systems. In this way we can learn about the physical and chemical conditions under which comets formed, and about the types of dynamical processing that shaped the solar system we see today. This paper summarizes some recent contributions to our understanding of both cometary volatiles and the composition, structure and evolution of protostellar disks.Comment: To appear in Space Science Reviews. The final publication is available at Springer via http://dx.doi.org/10.1007/s11214-015-0167-

Cigarette Smoke Exposure Alters mSin3a and Mi-2α/β Expression; implications in the control of pro-inflammatory gene transcription and glucocorticoid function

<p>Abstract</p> <p>Background</p> <p>The key co-repressor complex components HDAC-2, Mi-2α/β and mSin3a are all critical to the regulation of gene transcription. HDAC-2 function is impaired by oxidative stress in a PI3Kδ dependant manner which may be involved in the chronic glucocorticoid insensitive inflammation in the lungs of COPD patients. However, the impact of cigarette smoke exposure on the expression of mSin3a and Mi2α/β and their role in glucocorticoid responsiveness is unknown.</p> <p>Methods</p> <p>Wild type, PI3Kγ knock-out (PI3Kγ^-/-) and PI3K kinase dead knock-in (PI3Kδ^D910/A910) transgenic mice were exposed to cigarette smoke for 3 days and the expression levels of the co-repressor complex components HDAC-2, mSin3a, Mi-2α and Mi-2β and HDAC-2 activity in the lungs were assessed.</p> <p>Results</p> <p>Cigarette smoke exposure impaired glucocorticoid function and reduced HDAC-2 activity which was protected in the PI3Kδ^D910/A910mice. Both mSin3a and Mi-2α protein expression was reduced in smoke-exposed mice. Budesonide alone protected mSin3a protein expression with no additional effect seen with abrogation of PI3Kγ/δ activity, however Mi-2α, but not Mi-2β, expression was protected in both PI3Kδ^D910/A910and PI3Kγ^-/-budesonide-treated smoke-exposed mice. The restoration of glucocorticoid function coincided with the protection of both HDAC activity and mSin3a and Mi-2α protein expression.</p> <p>Conclusions</p> <p>Cigarette smoke exposure induced glucocorticoid insensitivity and alters co-repressor activity and expression which is prevented by blockade of PI3K signaling with glucocorticoid treatment. Inhibition of PI3Kδ signalling in combination with glucocorticoid treatment may therefore provide a therapeutic strategy for restoring oxidant-induced glucocortiocid unresponsiveness.</p

Insetos em presépios e as "formigas vestidas" de Jules Martin (1832-1906): uma curiosa manufatura paulistana do final do século XIX

Encontrados no Brasil desde os primórdios da colonização portuguesa, os presépios logo tiveram de adaptar-se à realidade local, circunstância muito propícia ao aparecimento de concepções heterodoxas e ao emprego de elementos exóticos da fauna e flora de cada região. Como registros envolvendo insetos são muito pouco comuns, chama a atenção que fêmeas de saúva, Atta sp. (Hymenoptera, Formicidae), tenham sido aproveitadas na composição de presépios no estado de São Paulo. Tendo subsistido pelo menos até a década 1960, os "presépios de formigas" existentes em cidades como Embu das Artes poderiam estar relacionados às "formigas vestidas" criadas por Jules Martin, curiosa manufatura paulistana do último quartel do século XIX.Present in Brazil since the beginning of Portuguese colonization, crèche nativity scenes were soon adapted to local reality, a propitious circumstance for the appearance of heterodox conceptions and the use of exotic elements of the fauna and flora peculiar to each region. As records about insects are very uncommon, it is noteworthy that females of leaf-cutting ants, Atta sp. (Hymenoptera, Formicidae), were used to compose crèche nativity scenes in São Paulo State. Having subsisted at least up to the decade of 1960, the "ant crèches" of cities such as Embu das Artes could be related to the then famous "dressed ants" created by Jules Martin, a curious manufacture of the city of São Paulo in the last quarter of the 19th century

In vitro nuclear interactome of the HIV-1 Tat protein

<p>Abstract</p> <p>Background</p> <p>One facet of the complexity underlying the biology of HIV-1 resides not only in its limited number of viral proteins, but in the extensive repertoire of cellular proteins they interact with and their higher-order assembly. HIV-1 encodes the regulatory protein Tat (86–101aa), which is essential for HIV-1 replication and primarily orchestrates HIV-1 provirus transcriptional regulation. Previous studies have demonstrated that Tat function is highly dependent on specific interactions with a range of cellular proteins. However they can only partially account for the intricate molecular mechanisms underlying the dynamics of proviral gene expression. To obtain a comprehensive nuclear interaction map of Tat in T-cells, we have designed a proteomic strategy based on affinity chromatography coupled with mass spectrometry.</p> <p>Results</p> <p>Our approach resulted in the identification of a total of 183 candidates as Tat nuclear partners, 90% of which have not been previously characterised. Subsequently we applied <it>in silico </it>analysis, to validate and characterise our dataset which revealed that the Tat nuclear interactome exhibits unique signature(s). First, motif composition analysis highlighted that our dataset is enriched for domains mediating protein, RNA and DNA interactions, and helicase and ATPase activities. Secondly, functional classification and network reconstruction clearly depicted Tat as a polyvalent protein adaptor and positioned Tat at the nexus of a densely interconnected interaction network involved in a range of biological processes which included gene expression regulation, RNA biogenesis, chromatin structure, chromosome organisation, DNA replication and nuclear architecture.</p> <p>Conclusion</p> <p>We have completed the <it>in vitro </it>Tat nuclear interactome and have highlighted its modular network properties and particularly those involved in the coordination of gene expression by Tat. Ultimately, the highly specialised set of molecular interactions identified will provide a framework to further advance our understanding of the mechanisms of HIV-1 proviral gene silencing and activation.</p

KD5170, a novel mercaptoketone-based histone deacetylase inhibitor that exhibits broad spectrum antitumor activity in vitro and in vivo

Abstract Histone deacetylase (HDAC) inhibitors have garnered significant attention as cancer drugs. These therapeutic agents have recently been clinically validated with the market approval of vorinostat (SAHA, Zolinza) for treatment of cutaneous T-cell lymphoma. Like vorinostat, most of the small-molecule HDAC inhibitors in clinical development are hydroxamic acids, whose inhibitory activity stems from their ability to coordinate the catalytic Zn 2+ in the active site of HDACs. We sought to identify novel, nonhydroxamate-based HDAC inhibitors with potentially distinct pharmaceutical properties via an ultra-high throughput small molecule biochemical screen against the HDAC activity in a HeLa cell nuclear extract. An A-mercaptoketone series was identified and chemically optimized. The lead compound, KD5170, exhibits HDAC inhibitory activity with an IC 50 of 0.045 Mmol/L in the screening biochemical assay and an EC 50 of 0.025 Mmol/L in HeLa cell -based assays that monitor histone H3 acetylation. KD5170 also exhibits broad spectrum classe