279 research outputs found

    State-resolved rotational cross sections and thermal rate coefficients for ortho-/para-H2+HD at low temperatures and HD+HD elastic scattering

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    Results for quantum mechanical calculations of the integral cross sections and corresponding thermal rate coefficients for para-/ortho-H2+HD collisions are presented. Because of significant astrophysical interest in regard to the cooling of primodial gas the low temperature limit of para-/ortho-H2+HD is investigated. Sharp resonances in the rotational state-resolved cross sections have been calculated at low energies. These resonances are important and significantly contribute to the corresponding rotational state-resolved thermal rate coefficients, particularly at low temperatures, that is less than T∼100T \sim 100K. Additionally in this work, the cross sections for the elastic HD+HD collision have also been calculated. We obtained quite satisfactory agreement with the results of other theoretical works and experiments.Comment: 16 pages, 5 figures, additional results include

    Bioconductor: open software development for computational biology and bioinformatics.

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    The Bioconductor project is an initiative for the collaborative creation of extensible software for computational biology and bioinformatics. The goals of the project include: fostering collaborative development and widespread use of innovative software, reducing barriers to entry into interdisciplinary scientific research, and promoting the achievement of remote reproducibility of research results. We describe details of our aims and methods, identify current challenges, compare Bioconductor to other open bioinformatics projects, and provide working examples

    Mio-Pliocene Faunal Exchanges and African Biogeography: The Record of Fossil Bovids

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    The development of the Ethiopian biogeographic realm since the late Miocene is here explored with the presentation and review of fossil evidence from eastern Africa. Prostrepsiceros cf. vinayaki and an unknown species of possible caprin affinity are described from the hominid-bearing Asa Koma and Kuseralee Members (∼5.7 and ∼5.2 Ma) of the Middle Awash, Ethiopia. The Middle Awash Prostrepsiceros cf. vinayaki constitutes the first record of this taxon from Africa, previously known from the Siwaliks and Arabia. The possible caprin joins a number of isolated records of caprin or caprin-like taxa recorded, but poorly understood, from the late Neogene of Africa. The identification of these two taxa from the Middle Awash prompts an overdue review of fossil bovids from the sub-Saharan African record that demonstrate Eurasian affinities, including the reduncin Kobus porrecticornis, and species of Tragoportax. The fossil bovid record provides evidence for greater biological continuity between Africa and Eurasia in the late Miocene and earliest Pliocene than is found later in time. In contrast, the early Pliocene (after 5 Ma) saw the loss of any significant proportions of Eurasian-related taxa, and the continental dominance of African-endemic taxa and lineages, a pattern that continues today

    Analysis of vertical ground loop heat exchangers applied to buildings in the UK

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    The work presented here deals with the design and performance of ground-source heat pumps and ground-sink cooling systems using vertical borehole arrays for commercial applications in the UK. Heating and cooling energy demands for a range of building and HVAC plant options are obtained by thermal modelling applied to four HVAC plant options: space heating only; heating with chilled ceilings; fan coil units and constant volume all-air plant. Ground loop designs are conducted for each system option using an impulse-response method and the parameters extracted from this are used in 10-year simulations of plant response which have been carried out using HVACSIM+. The 10-year time horizon was used to assess any degradation in earth temperature over time. The results show that a substantial reduction in energy (and, hence, carbon) can be expected of up to and exceeding 50% when using ground source heat pumps for winter heating with direct cooling in summer in association with moderate temperature cooling systems such as chilled ceilings. A degradation of earth temperature was evident with systems utilising limited cooling or no cooling but this did not appear to influence heat pump performance greatly. Practical Applications: Design and performance data for use in vertical ground loop (borehole) heat exchanger arrays providing source heat for heat pumps as well as direct cooling for buildings are generated and reported in this paper. The data should be of help to design practitioners for the sizing of borehole arrays for both heating and cooling. Design and performance matching to a wide variety of HVAC combinations, building energy demand levels and two contrasting sets of earth thermal property data are included so that practitioners will be able to select results that suit a range of modern applications. Also included are results of 10-year energy simulations that demonstrate the required design and operating conditions needed to ensure that initial undisturbed earth conditions will not drift with time to an unacceptable extent. Comparisons are made with conventional heating and cooling methods so that estimates of carbon savings due to the use of ground-coupled heat pumps with (and without) direct cooling can be made

    Snarky Signatures: Minimal Signatures of Knowledge from Simulation-Extractable SNARKs

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    We construct a pairing based simulation-extractable SNARK (SE-SNARK) that consists of only 3 group elements and has highly efficient verification. By formally linking SE-SNARKs to signatures of knowledge, we then obtain a succinct signature of knowledge consisting of only 3 group elements. SE-SNARKs enable a prover to give a proof that they know a witness to an instance in a manner which is: (1) succinct - proofs are short and verifier computation is small; (2) zero-knowledge - proofs do not reveal the witness; (3) simulation-extractable - it is only possible to prove instances to which you know a witness, even when you have already seen a number of simulated proofs. We also prove that any pairing based signature of knowledge or SE-NIZK argument must have at least 3 group elements and 2 verification equations. Since our constructions match these lower bounds, we have the smallest size signature of knowledge and the smallest size SE-SNARK possible

    High pre-diagnosis inflammation-related risk score associated with decreased ovarian cancer survival

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    BACKGROUND: There is suggestive evidence that inflammation is related to ovarian cancer survival. However, more research is needed to identify inflammation-related factors that are associated with ovarian cancer survival and to determine their combined effects. METHODS: This analysis used pooled data on 8,147 women with invasive epithelial ovarian cancer from the Ovarian Cancer Association Consortium. Pre-diagnosis inflammatory-related exposures of interest included alcohol use, aspirin use, other nonsteroidal anti-inflammatory drug use, body mass index, environmental tobacco smoke exposure, history of pelvic inflammatory disease, polycystic ovarian syndrome, and endometriosis, menopausal hormone therapy use, physical inactivity, smoking status, and talc use. Using Cox proportional hazards (PH) models, the relationship between each exposure and survival was assessed in 50% of the data. A weighted inflammation-related risk score (IRRS) was developed and its association with survival was assessed using Cox PH models in the remaining 50% of the data. RESULTS: There was a statistically significant trend of increasing risk of death per quartile of the IRRS (HR=1.09, 95% CI 1.03-1.14). Women in the upper quartile of the IRRS had 31% higher death rate compared to the lowest quartile (95% CI 1.11-1.54). CONCLUSIONS: A higher pre-diagnosis IRRS was associated with increased mortality risk after an ovarian cancer diagnosis. Further investigation is warranted to evaluate whether post-diagnosis exposures are also associated with survival. IMPACT: Given that pre- and post-diagnosis exposures are often correlated and many are modifiable, our study results can ultimately motivate the development of behavioral recommendations to enhance survival among ovarian cancer patients

    All You Can Eat: High Performance Capacity and Plasticity in the Common Big-Eared Bat, Micronycteris microtis (Chiroptera: Phyllostomidae)

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    Ecological specialization and resource partitioning are expected to be particularly high in the species-rich communities of tropical vertebrates, yet many species have broader ecological niches than expected. In Neotropical ecosystems, Neotropical leaf-nosed bats (Phyllostomidae) are one of the most ecologically and functionally diverse vertebrate clades. Resource partitioning in phyllostomids might be achieved through differences in the ability to find and process food. We selected Micronycteris microtis, a very small (5–7 g) animalivorous phyllostomid, to explore whether broad resource use is associated with specific morphological, behavioral and performance traits within the phyllostomid radiation. We documented processing of natural prey and measured bite force in free-ranging M. microtis and other sympatric phyllostomids. We found that M. microtis had a remarkably broad diet for prey size and hardness. For the first time, we also report the consumption of vertebrates (lizards), which makes M. microtis the smallest carnivorous bat reported to date. Compared to other phyllostomids, M. microtis had the highest bite force for its size and cranial shape and high performance plasticity. Bite force and cranial shape appear to have evolved rapidly in the M. microtis lineage. High performance capacity and high efficiency in finding motionless prey might be key traits that allow M. microtis, and perhaps other species, to successfully co-exist with other gleaning bats

    Luminal-Applied Flagellin Is Internalized by Polarized Intestinal Epithelial Cells and Elicits Immune Responses via the TLR5 Dependent Mechanism

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    Bacteria release flagellin that elicits innate responses via Toll-like receptor 5 (TLR5). Here, we investigated the fate of apically administrated full length flagellin from virulent and avirulent bacteria, along with truncated recombinant flagellin proteins in intestinal epithelial cells and cellular responses. Flagellin was internalized by intestinal epithelial cell (IEC) monolayers of IEC-18. Additionally, apically applied flagellin was internalized by polarized human Caco-2BBe and T-84 cells in a TLR5 dependent mechanism. More, flagellin exposure did not affect the integrity of intestinal monolayers. With immunofluorescent staining, internalized flagellin was detected in both early endosomes as well as lysosomes. We found that apical exposure of polarized Caco-2BBe and T-84 to flagellin from purified Salmonella, Escherichia coli O83:H1 (isolate from Crohn’s lesion) or avirulent E. coli K12 induced comparable levels of basolateral IL-8 secretion. A recombinant protein representing the conserved amino (N) and carboxyl (C) domains (D) of the flagellin protein (ND1/2ECHCD2/1) induced IL-8 secretion from IEC similar to levels elicited by full-length flagellins. However, a recombinant flagellin protein containing only the D3 hypervariable region elicited no IL-8 secretion in both cell lines compared to un-stimulated controls. Silencing or blocking TLR5 in Caco-2BBe cells resulted in a lack of flagellin internalization and decreased IL-8 secretion. Furthermore, apical exposure to flagellin stimulated transepithelial migration of neutrophils and dendritic cells. The novel findings in this study show that luminal-applied flagellin is internalized by normal IEC via TLR5 and co-localizes to endosomal and lysosomal compartments where it is likely degraded as flagellin was not detected on the basolateral side of IEC cultures

    A Therapeutic Antibody against West Nile Virus Neutralizes Infection by Blocking Fusion within Endosomes

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    Defining the precise cellular mechanisms of neutralization by potently inhibitory antibodies is important for understanding how the immune system successfully limits viral infections. We recently described a potently inhibitory monoclonal antibody (MAb E16) against the envelope (E) protein of West Nile virus (WNV) that neutralizes infection even after virus has spread to the central nervous system. Herein, we define its mechanism of inhibition. E16 blocks infection primarily at a post-attachment step as antibody-opsonized WNV enters permissive cells but cannot escape from endocytic compartments. These cellular experiments suggest that E16 blocks the acid-catalyzed fusion step that is required for nucleocapsid entry into the cytoplasm. Indeed, E16 directly inhibits fusion of WNV with liposomes. Additionally, low-pH exposure of E16–WNV complexes in the absence of target membranes did not fully inactivate infectious virus, further suggesting that E16 prevents a structural transition required for fusion. Thus, a strongly neutralizing anti–WNV MAb with therapeutic potential is potently inhibitory because it blocks viral fusion and thereby promotes clearance by delivering virus to the lysosome for destruction

    Analysis of Epitopes on Dengue Virus Envelope Protein Recognized by Monoclonal Antibodies and Polyclonal Human Sera by a High Throughput Assay

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    Dengue virus is the leading cause of arboviral diseases worldwide. The envelope protein is the major target of neutralizing antibodies and vaccine development. While previous studies have reported several epitopes on envelope protein, the possibility of interdomain epitopes and the relationship of epitopes to neutralizing potency remain unexplored. We developed a high throughput dot blot assay by using 67 alanine mutants of surface-exposed envelope residues as a systematic approach to identify epitopes recognized by mouse monoclonal antibodies and polyclonal human sera. Our results suggested the presence of interdomain epitopes more frequent than previously appreciated. Compared with monoclonal antibodies generated by traditional protocol, the potent neutralizing monoclonal antibodies generated by a new protocol showed several unique features of their epitopes. Moreover, the predominant epitopes of antibodies against envelope protein in polyclonal sera can be identified by this assay. These findings have implications for future development of epitope-specific diagnostics and epitope-based dengue vaccine, and add to our understanding of humoral immune responses to dengue virus at the epitope level
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