Structural and stratigraphic evaluation of the southern Belgian anticline area, north Midway-Sunset field, San Joaquin Basin, California

Accompanied by 13 folded plates in pocket.Thesis (M.S.)--University of Oklahoma, 2007.Includes bibliographical references (leaves 208-213).The Midway-Sunset field is located in the West Side fold belt in the San Joaquin Basin of California. The structures in the area, including the Midway-Sunset, Buena Vista, and Elk Hills anticlines, were formed during multiple episodes of compressive deformation, separated by periods of extension, between the Upper Miocene and present. A regional study of a 250 square mile area was conducted to understand the structure and stratigraphy within the fields on these structures. The study utilized existing geologic maps and data from over 400 wells to construct three regional structural and seven stratigraphic cross sections. One of the structural sections was kinematically reconstructed through time to understand the tectonic history. The Midway-Sunset and Buena Vista structures are interpreted as a series of parallel, fault-bounded structures, cored by deeper fault-bend folds. Many of the larger structures display overturned or steep flanks. Some of the reservoir units, such as the Stevens and Potter deep water turbidite sandstones, were deposited in an active tectonic environment, so that the depositional history is closely related to the structural events. A more detailed structural-stratigraphic study was conducted to evaluate an approximately 15 square mile area within the Southern Belgian anticline. A three-dimensional structural model was constructed using five closely-spaced balanced structural cross sections constrained by dipmeter logs and surface structural data. This structural model will provide a tool to evaluate potential bypassed reservoirs in the Potter Sandstone, and new targets in deeper reservoirs

Ladyzhenskaya-Prodi-Serrin condition for fluid-structure interaction systems

We consider the interaction of a viscous incompressible fluid with a flexible shell in three space dimensions. The fluid is described by the three-dimensional incompressible Navier--Stokes equations in a domain that is changing in accordance with the motion of the structure. The displacement of the latter evolves along a visco-elastic shell equation. Both are coupled through kinematic boundary conditions and the balance of forces. We prove a counterpart of the classical Ladyzhenskaya-Prodi-Serrin condition yielding conditional regularity and uniqueness of a solution. Our result is a consequence of the following three ingredients which might be of independent interest: {\bf (i)} the existence of local strong solutions, {\bf (ii)} an acceleration estimate (under the Serrin assumption) ultimately controlling the second-order energy norm, and {\bf (iii)} a weak-strong uniqueness theorem. The first point, and to some extent, the last point were previously known for the case of elastic plates, which means that the relaxed state is flat. We extend these results to the case of visco-elastic shells, which means that more general reference geometries are considered such as cylinders or spheres. The second point, i.e. the acceleration estimate for three-dimensional fluids is new even in the case of plates.Comment: 42 page

COVID-19 Severity in Obesity: Leptin and Inflammatory Cytokine Interplay in the Link Between High Morbidity and Mortality

Obesity is one of the foremost risk factors in coronavirus infection resulting in severe illness and mortality as the pandemic progresses. Obesity is a well-known predisposed chronic inflammatory condition. The dynamics of obesity and its impacts on immunity may change the disease severity of pneumonia, especially in acute respiratory distress syndrome, a primary cause of death from SARS-CoV-2 infection. The adipocytes of adipose tissue secret leptin in proportion to individuals’ body fat mass. An increase in circulating plasma leptin is a typical characteristic of obesity and correlates with a leptin-resistant state. Leptin is considered a pleiotropic molecule regulating appetite and immunity. In immunity, leptin functions as a cytokine and coordinates the host’s innate and adaptive responses by promoting the Th1 type of immune response. Leptin induced the proliferation and functions of antigen-presenting cells, monocytes, and T helper cells, subsequently influencing the pro-inflammatory cytokine secretion by these cells, such as TNF-α, IL-2, or IL-6. Leptin scarcity or resistance is linked with dysregulation of cytokine secretion leading to autoimmune disorders, inflammatory responses, and increased susceptibility towards infectious diseases. Therefore, leptin activity by leptin long-lasting super active antagonist’s dysregulation in patients with obesity might contribute to high mortality rates in these patients during SARS-CoV-2 infection. This review systematically discusses the interplay mechanism between leptin and inflammatory cytokines and their contribution to the fatal outcomes in COVID-19 patients with obesity

Expectations for time-delay measurements in active galactic nuclei with the Vera Rubin Observatory

The Vera Rubin Observatory will provide an unprecedented set of time-dependent observations of the sky. The planned Legacy Survey of Space and Time (LSST) operating for 10 years will provide dense lightcurves for thousands of active galactic nuclei (AGN) in Deep Drilling Fields (DDFs) and less dense lightcurves for millions of AGN. We model the prospects for measuring time delays for emission lines with respect to the continuum, using these data. We model the artificial lightcurves using Timmer-Koenig algorithm, we use the exemplary cadence to sample them, we supplement lightcurves with the expected contamination by the strong emission lines (Hbeta, Mg II and CIV as well as with Fe II pseudo-continuum and the starlight). We choose the suitable photometric bands appropriate for the redshift and compare the assumed line time delay with the recovered time delay for 100 statistical realizations of the light curves. We show that time delays for emission lines can be well measured from the Main Survey for the bright tail of the quasar distribution (about 15% of all sources) with the accuracy within 1 sigma error, for DDFs results for fainter quasars are also reliable when all 10 years of data are used. There are also some prospects to measure the time delays for the faintest quasars at the smallest redshifts from the first two years of data, and eventually even from the first season. The entire quasar population will allow obtaining results of apparently high accuracy but in our simulations, we see a systematic offset between the assumed and recovered time delay depending on the redshift and source luminosity which will not disappear even in the case of large statistics. Such a problem might affect the slope of the radius-luminosity relation and cosmological applications of quasars if simulations correcting for such effects are not performed.Comment: Submitted to Astronomy & Astrophysics, comments wellcom

Most viral peptides displayed by class I MHC on infected cells are immunogenic

CD8+ T cells are essential effectors in antiviral immunity, recognizing short virus-derived peptides presented by MHC class I (pMHCI) on the surface of infected cells. However, the fraction of viral pMHCI on infected cells that are immunogenic has not been shown for any virus. To approach this fundamental question, we used peptide sequencing by high-resolution mass spectrometry to identify more than 170 vaccinia virus pMHCI presented on infected mouse cells. Next, we screened each peptide for immunogenicity in multiple virus-infected mice, revealing a wide range of immunogenicities. A surprisingly high fraction (>80%) of pMHCI were immunogenic in at least one infected mouse, and nearly 40% were immunogenic across more than half of the mice screened. The high number of peptides found to be immunogenic and the distribution of responses across mice give us insight into the specificity of antiviral CD8+ T cell responses.This work was supported by a Project Grant from the National Health and Medical Research Council Australia (NHMRC) (APP1084283) (to D.C.T., A.W.P., and N.P.C.); an NHMRC Senior Research Fellowship (APP1104329) (to D.C.T.); an NHMRC Principal Research Fellowship (APP1137739) (to A.W.P.); and a Viertel Fellowship, ARC Future Fellowship, and NHMRC Program Grant (APP1071916) (to N.L.L.G.)

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Recurrent adamantinomatous craniopharyngiomas show MAPK pathway activation, clonal evolution and rare <i>TP53 </i>-loss-mediated malignant progression

The two types of craniopharyngioma, adamantinomatous (ACP) and papillary (PCP), are clinically relevant tumours in children and adults. Although the biology of primary craniopharyngioma is starting to be unravelled, little is known about the biology of recurrence. To fill this gap in knowledge, we have analysed through methylation array, RNA sequencing and pERK1/2 immunohistochemistry a cohort of paired primary and recurrent samples (32 samples from 14 cases of ACP and 4 cases of PCP). We show the presence of copy number alterations and clonal evolution across recurrence in 6 cases of ACP, and analysis of additional whole genome sequencing data from the Children’s Brain Tumour Network confirms chromosomal arm copy number changes in at least 7/67 ACP cases. The activation of the MAPK/ERK pathway, a feature previously shown in primary ACP, is observed in all but one recurrent cases of ACP. The only ACP without MAPK activation is an aggressive case of recurrent malignant human craniopharyngioma harbouring a CTNNB1 mutation and loss of TP53. Providing support for a functional role of this TP53 mutation, we show that Trp53 loss in a murine model of ACP results in aggressive tumours and reduced mouse survival. Finally, we characterise the tumour immune infiltrate showing differences in the cellular composition and spatial distribution between ACP and PCP. Together, these analyses have revealed novel insights into recurrent craniopharyngioma and provided preclinical evidence supporting the evaluation of MAPK pathway inhibitors and immunomodulatory approaches in clinical trials in against recurrent ACP

Staphylococcus aureus small colony variants impair host immunity by activating host cell glycolysis and inducing necroptosis

Staphylococcus aureus small colony variants (SCVs) are frequently associated with chronic infection, yet they lack expression of many virulence determinants associated with the pathogenicity of wild-type strains. We found that both wild-type S. aureus and a ΔhemB SCV prototype potently activate glycolysis in host cells. Glycolysis and the generation of mitochondrial reactive oxygen species were sufficient to induce necroptosis, a caspase-independent mechanism of host cell death that failed to eradicate S. aureus and instead promoted ΔhemB SCV pathogenicity. To support ongoing glycolytic activity, the ΔhemB SCV induced over a 100-fold increase in the expression of fumC, which encodes an enzyme that catalyses the degradatin of fumarate, an inhibitor of glycolysis. Consistent with fumC-dependent depletion of local fumarate, the ΔhemB SCV failed to elicit trained immunity and protection from a secondary infectious challenge in the skin. The reliance of the S. aureus SCV population on glycolysis accounts for much of its role in the pathogenesis of S. aureus skin infection

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London