Fatigue behavior of materials for the sst - electron fractographic studies final report

Electron microscopic fractography to determine fatigue behavior of materials for supersonic transport - titanium, aluminum, molybdenum, and vanadiu

Sedimentology and isotope geochemistry of transitional evaporitic environments within arid continental settings : from erg to saline lakes

This research was supported by grants to RPP from the AAPG (Gustavus E. Archie Memorial Grant) and by the European Union’s Horizon 2020 research and innovation programme (Grant 678812 to M.W.C.).Arid continental basins typically contain a spectrum of coeval environments that coexist and interact from proximal to distal. Within the distal portion, aeolian ergs often border playa, or perennial, desert lakes, fed by fluvial incursions or elevated groundwaters. Evaporites are common features in these dryland, siliciclastic dominant settings. However, sedimentary controls upon evaporite deposition are not widely understood, especially within transitional zones between coeval clastic environments that are dominantly controlled by larger scale allocyclic processes, such as climate. The sulphur (δ34S) and oxygen (δ18O, Δ17O) isotope systematics of evaporites can reveal cryptic aspects of sedimentary cycling and sulphate sources in dryland settings. However, due to the lack of sedimentological understanding of evaporitic systems, isotopic data can be easily misinterpreted. This work presents detailed sedimentological and petrographic observations, coupled with δ34S, δ18O and Δ17O data, for the early Permian Cedar Mesa Sandstone Formation (western USA). Depositional models for mixed evaporitic / clastic sedimentation, which occurs either in erg-marginal or lacustrine-marginal settings, are presented to detail the sedimentary interactions present in terms of climate variations that control them. Sedimentological and petrographical analysis of the evaporites within the Cedar Mesa Sandstone Formation reveal a continental depositional environment and two end member depositional models have been developed: erg-margin and lake-margin. The δ34S values of gypsum deposits within the Cedar Mesa Sandstone Formation are consistent with late Carboniferous to early Permian marine settings. However, a marine interpretation is inconsistent with sedimentological and petrographic evidence. Consequently, δ34S, δ18O and Δ17O values are probably recycled and do not reflect ocean-atmosphere values at the time of evaporite precipitation. They are most likely derived from the weathering of older marine evaporites in the hinterland. Thus, the results demonstrate the need for a combination of both sedimentological and geochemical analysis of evaporitic systems to better understand their depositional setting and conditions.PostprintPeer reviewe

Repulsive Core of NN S-Wave Scattering in a Quark Model with a Condensed Vacuum

We work in a chiral invariant quark model, with a condensed vacuum, characterized by only one parameter. Bound state equations for the nucleon and Delta are solved in order to obtain an updated value of their radii and masses. Nucleon-nucleon S-Wave scattering is studied in the RGM framework both for isospin T=1 and T=0. The phase shifts are calculated and an equivalent local potential, which is consistent with K-N scattering, is derived. The result is a reasonable microscopic short range repulsion in the nucleon-nucleon interaction.Comment: 23 pages in latex revtex, 4 Postscript figure

Meson-Meson Scattering in the Quark Model: Spin Dependence and Exotic Channels

We apply a quark interchange model to spin-dependent and exotic meson-meson scattering. The model includes the complete set of standard quark model forces, including OGE spin-orbit and tensor and scalar confinement spin-orbit. Scattering amplitudes derived assuming SHO and Coulomb plus linear plus hyperfine meson wavefunctions are compared. In I=2 pi pi we find approximate agreement with the S-wave phase shift from threshold to 1.5 GeV, where we predict an extremum that is supported by the data. Near threshold we find rapid energy dependence that may reconcile theoretical estimates of small scattering lengths with experimental indications of larger ones based on extrapolation of measurements at moderate kpi^2. In PsV scattering we find that the quark-quark L*S and T forces map into L*S and T meson-meson interactions, and the P-wave L*S force is large. Finally we consider scattering in J^PC-exotic channels, and note that some of the Deck effect mechanisms suggested as possible nonresonant origins of the pi_1(1400) signal are not viable in this model.Comment: 51 pages, 10 figures, uses epsf.sty epsfig.st

Characterization of early host responses in adults with dengue disease

BACKGROUND: While dengue-elicited early and transient host responses preceding defervescence could shape the disease outcome and reveal mechanisms of the disease pathogenesis, assessment of these responses are difficult as patients rarely seek healthcare during the first days of benign fever and thus data are lacking. METHODS: In this study, focusing on early recruitment, we performed whole-blood transcriptional profiling on dengue virus PCR positive patients sampled within 72 h of self-reported fever presentation (average 43 h, SD 18.6 h) and compared the signatures with autologous samples drawn at defervescence and convalescence and to control patients with fever of other etiology. RESULTS: In the early dengue fever phase, a strong activation of the innate immune response related genes were seen that was absent at defervescence (4-7 days after fever debut), while at this second sampling genes related to biosynthesis and metabolism dominated. Transcripts relating to the adaptive immune response were over-expressed in the second sampling point with sustained activation at the third sampling. On an individual gene level, significant enrichment of transcripts early in dengue disease were chemokines CCL2 (MCP-1), CCL8 (MCP-2), CXCL10 (IP-10) and CCL3 (MIP-1α), antimicrobial peptide β-defensin 1 (DEFB1), desmosome/intermediate junction component plakoglobin (JUP) and a microRNA which may negatively regulate pro-inflammatory cytokines in dengue infected peripheral blood cells, mIR-147 (NMES1). CONCLUSIONS: These data show that the early response in patients mimics those previously described in vitro, where early assessment of transcriptional responses has been easily obtained. Several of the early transcripts identified may be affected by or mediate the pathogenesis and deserve further assessment at this timepoint in correlation to severe disease

Surfactant protein D inhibits HIV-1 infection of target cells via interference with gp120-CD4 interaction and modulates pro-inflammatory cytokine production

© 2014 Pandit et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Surfactant Protein SP-D, a member of the collectin family, is a pattern recognition protein, secreted by mucosal epithelial cells and has an important role in innate immunity against various pathogens. In this study, we confirm that native human SP-D and a recombinant fragment of human SP-D (rhSP-D) bind to gp120 of HIV-1 and significantly inhibit viral replication in vitro in a calcium and dose-dependent manner. We show, for the first time, that SP-D and rhSP-D act as potent inhibitors of HIV-1 entry in to target cells and block the interaction between CD4 and gp120 in a dose-dependent manner. The rhSP-D-mediated inhibition of viral replication was examined using three clinical isolates of HIV-1 and three target cells: Jurkat T cells, U937 monocytic cells and PBMCs. HIV-1 induced cytokine storm in the three target cells was significantly suppressed by rhSP-D. Phosphorylation of key kinases p38, Erk1/2 and AKT, which contribute to HIV-1 induced immune activation, was significantly reduced in vitro in the presence of rhSP-D. Notably, anti-HIV-1 activity of rhSP-D was retained in the presence of biological fluids such as cervico-vaginal lavage and seminal plasma. Our study illustrates the multi-faceted role of human SPD against HIV-1 and potential of rhSP-D for immunotherapy to inhibit viral entry and immune activation in acute HIV infection. © 2014 Pandit et al.The work (Project no. 2011-16850) was supported by Medical Innovation Fund of Indian Council of Medical Research, New Delhi, India (www.icmr.nic.in/)

Synergistic Interactions between the NS3hel and E Proteins Contribute to the Virulence of Dengue Virus Type 1

Dengue virus constitutes a significant public health problem in tropical regions of the world. Despite the high morbidity and mortality of this infection, no effective antiviral drugs or vaccines are available for the treatment or prevention of dengue infections. The profile of clinical signs associated with dengue infection has changed in recent years with an increase in the number of episodes displaying unusual signs. We use reverse genetics technology to engineer DENV-1 viruses with subsets of mutations previously identified in highly neurovirulent strains to provide insights into the molecular mechanisms underlying dengue neuropathogenesis. We found that single mutations affecting the E and NS3hel proteins, introduced in a different genetic context, had a synergistic effect increasing DENV replication capacity in human and mosquito derived cells in vitro. We also demonstrated correlations between the presence of these mutations and viral replication efficiency, viral loads, the induction of innate immune response genes and pathogenesis in a mouse model. These results should improve our understanding of the DENV-host cell interaction and contribute to the development of effective antiviral strategies

Phase control and measurement in digital microscopy

The ongoing merger of the digital and optical components of the modern microscope is creating opportunities for new measurement techniques, along with new challenges for optical modelling. This thesis investigates several such opportunities and challenges which are particularly relevant to biomedical imaging. Fourier optics is used throughout the thesis as the underlying conceptual model, with a particular emphasis on three--dimensional Fourier optics. A new challenge for optical modelling provided by digital microscopy is the relaxation of traditional symmetry constraints on optical design. An extension of optical transfer function theory to deal with arbitrary lens pupil functions is presented in this thesis. This is used to chart the 3D vectorial structure of the spatial frequency spectrum of the intensity in the focal region of a high aperture lens when illuminated by linearly polarised beam. Wavefront coding has been used successfully in paraxial imaging systems to extend the depth of field. This is achieved by controlling the pupil phase with a cubic phase mask, and thereby balancing optical behaviour with digital processing. In this thesis I present a high aperture vectorial model for focusing with a cubic phase mask, and compare it with results calculated using the paraxial approximation. The effect of a refractive index change is also explored. High aperture measurements of the point spread function are reported, along with experimental confirmation of high aperture extended depth of field imaging of a biological specimen. Differential interference contrast is a popular method for imaging phase changes in otherwise transparent biological specimens. In this thesis I report on a new isotropic algorithm for retrieving the phase from differential interference contrast images of the phase gradient, using phase shifting, two directions of shear, and non--iterative Fourier phase integration incorporating a modified spiral phase transform. This method does not assume that the specimen has a constant amplitude. A simulation is presented which demonstrates good agreement between the retrieved phase and the phase of the simulated object, with excellent immunity to imaging noise

Activation and modulation of antiviral and apoptotic genes in pigs infected with classical swine fever viruses of high, moderate or low virulence

The immune response to CSFV and the strategies of this virus to evade and suppress the pigs’ immune system are still poorly understood. Therefore, we investigated the transcriptional response in the tonsils, median retropharyngeal lymph node (MRLN), and spleen of pigs infected with CSFV strains of similar origin with high, moderate, and low virulence. Using a porcine spleen/intestinal cDNA microarray, expression levels in RNA pools prepared from infected tissue at 3 dpi (three pigs per virus strain) were compared to levels in pools prepared from uninfected homologue tissues (nine pigs). A total of 44 genes were found to be differentially expressed. The genes were functionally clustered in six groups: innate and adaptive immune response, interferon-regulated genes, apoptosis, ubiquitin-mediated proteolysis, oxidative phosphorylation and cytoskeleton. Significant up-regulation of three IFN-γ-induced genes in the MRLNs of pigs infected with the low virulence strain was the only clear qualitative difference in gene expression observed between the strains with high, moderate and low virulence. Real-time PCR analysis of four response genes in all individual samples largely confirmed the microarray data at 3 dpi. Additional PCR analysis of infected tonsil, MRLN, and spleen samples collected at 7 and 10 dpi indicated that the strong induction of expression of the antiviral response genes chemokine CXCL10 and 2′–5′ oligoadenylate synthetase 2, and of the TNF-related apoptosis-inducing ligand (TRAIL) gene at 3 dpi, decreased to lower levels at 7 and 10 dpi. For the highly and moderately virulent strains, this decrease in antiviral and apoptotic gene expression coincided with higher levels of virus in these immune tissues

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)