Complex algebraic compactifications of the moduli space of Hermitian-Yang-Mills connections on a projective manifold

In this paper we study the relationship between three compactifications of the moduli space of Hermitian-Yang-Mills connections on a fixed Hermitian vector bundle over a projective algebraic manifold of arbitrary dimension. Via the Donaldson-Uhlenbeck-Yau theorem, this space is analytically isomorphic to the moduli space of stable holomorphic vector bundles, and as such it admits an algebraic compactification by Gieseker-Maruyama semistable torsion-free sheaves. A recent construction due to the first and third authors gives another compactification as a moduli space of slope semistable sheaves. In the present article, following fundamental work of Tian generalising the analysis of Uhlenbeck and Donaldson in complex dimension two, we define a gauge theoretic compactification by adding certain ideal connections at the boundary. Extending work of Jun Li in the case of bundles on algebraic surfaces, we exhibit comparison maps from the sheaf theoretic compactifications and prove their continuity. The continuity, together with a delicate analysis of the fibres of the map from the moduli space of slope semistable sheaves allows us to endow the gauge theoretic compactification with the structure of a complex analytic space.Comment: minor changes to the exposition based on referee's comments; final version to appear in Geometry & Topology; 95 page

Experimental Investigation of Unsteady Thrust Augmentation Using a Speaker-Driven Jet

An experimental investigation is described in which a simple speaker-driven jet was used as a pulsed thrust source (driver) for an ejector configuration. The objectives of the investigation were twofold. The first was to expand the experimental body of evidence showing that an unsteady thrust source, combined with a properly sized ejector generally yields higher thrust augmentation values than a similarly sized, steady driver of equivalent thrust. The second objective was to identify characteristics of the unsteady driver that may be useful for sizing ejectors, and for predicting the thrust augmentation levels that may be achieved. The speaker-driven jet provided a convenient source for the investigation because it is entirely unsteady (i.e., it has no mean velocity component) and because relevant parameters such as frequency, time-averaged thrust, and diameter are easily variable. The experimental setup will be described, as will the two main measurements techniques employed. These are thrust and digital particle imaging velocimetry of the driver. It will be shown that thrust augmentation values as high as 1.8 were obtained, that the diameter of the best ejector scaled with the dimensions of the emitted vortex, and that the so-called formation time serves as a useful dimensionless parameter by which to characterize the jet and predict performance

FE-SEM, FIB and TEM Study of Surface Deposits of Apollo 15 Green Glass Volcanic Spherules

Surface deposits on lunar pyroclastic green (Apollo 15) and orange (Apollo 17) glass spherules have been attributed to condensation from the gas clouds that accompanied fire-fountain eruptions. The fire fountains cast molten lava high above the lunar surface and the silicate melt droplets quenched before landing producing the glass beads. Early investigations showed that these deposits are rich in sulfur and zinc. The deposits are extremely fine-grained and thin, so that it was never possible to determine their chemical compositions cleanly by SEM/EDX or electron probe x-ray analysis because most of the excited volume was in the under-lying silicate glass. We are investigating the surface deposits by TEM, using focused ion beam (FIB) microscopy to extract and thin the surface deposits. Here we report on chemical mapping of a FIB section of surface deposits of an Apollo green glass bead 15401using the ultra-high resolution JEOL 2500 STEM located at NASA Johnson Space Center

Light chain 2 is a Tctex-type related axonemal dynein light chain that regulates directional ciliary motility in \u3ci\u3eTrypanosoma brucei\u3c/i\u3e

Flagellar motility is essential for the cell morphology, viability, and virulence of pathogenic kinetoplastids. Trypanosoma brucei flagella beat with a bending wave that propagates from the flagellum’s tip to its base, rather than base-to-tip as in other eukaryotes. Thousands of dynein motor proteins coordinate their activity to drive ciliary bending wave propagation. Dynein-associated light and intermediate chains regulate the biophysical mechanisms of axonemal dynein. Tctex-type outer arm dynein light chain 2 (LC2) regulates flagellar bending wave propagation direction, amplitude, and frequency in Chlamydomonas reinhardtii. However, the role of Tctex-type light chains in regulating T. brucei motility is unknown. Here, we used a combination of bioinformatics, in-situ molecular tagging, and immunofluorescence microscopy to identify a Tctex-type light chain in the procyclic form of T. brucei (TbLC2). We knocked down TbLC2 expression using RNAi in both wild-type and FLAM3, a flagellar attachment zone protein, knockdown cells and quantified TbLC2’s effects on trypanosome cell biology and biophysics. We found that TbLC2 knockdown reduced the directional persistence of trypanosome cell swimming, induced an asymmetric ciliary bending waveform, modulated the bias between the base-to-tip and tip-to-base beating modes, and increased the beating frequency. Together, our findings are consistent with a model of TbLC2 as a down-regulator of axonemal dynein activity that stabilizes the forward tip-to-base beating ciliary waveform characteristic of trypanosome cells. Our work sheds light on axonemal dynein regulation mechanisms that contribute to pathogenic kinetoplastids’ unique tip-to-base ciliary beating nature and how those mechanisms underlie dynein-driven ciliary motility more generally

An Optimized Cell-Based Assay To Assess Influenza Virus Replication by Measuring Neuraminidase Activity and Its Applications for Virological Surveillance

Year-round virological characterization of circulating epidemic influenza viruses is conducted worldwide to detect the emergence of viruses that may escape pre-existing immunity or acquire resistance to antivirals. High throughput phenotypic assays are needed to complement the sequence-based analysis of circulating viruses and improve pandemic preparedness. The recent entry of a polymerase inhibitor, baloxavir, into the global market further highlighted this need. Here, we optimized a cell-based assay that considerably streamlines antiviral and antigenic testing by replacing lengthy immunostaining and imaging procedures used in current assay with measuring the enzymatic activity of nascent neuraminidase (NA) molecules expressed on the surface of virus-infected cells. For convenience, this new assay was named IRINA (Influenza Replication Inhibition Neuraminidase-based Assay). IRINA was successfully validated to assess inhibitory activity of baloxavir on virus replication by testing a large set (\u3e150) of influenza A and B viruses, including drug resistant strains and viruses collected during 2017–2022. To test its versatility, IRINA was utilized to evaluate neutralization activity of a broadly reactive human anti-HA monoclonal antibody, FI6, and post-infection ferret antisera, as well as the inhibition of NA enzyme activity by NA inhibitors. Performance of IRINA was tested in parallel using respective conventional assays. IRINA offers an attractive alternative to current phenotypic assays, while maintaining reproducibility and high throughput capacity. Additionally, the improved turnaround time may prove to be advantageous when conducting time sensitive studies, such as investigating a new virus outbreak. This assay can meet the needs of surveillance laboratories by providing a streamlined and cost-effective approach for virus characterization

Antiviral responses by swine primary bronchoepithelial cells are limited compared to human bronchoepithelial cells following influenza virus infection

Swine generate reassortant influenza viruses because they can be simultaneously infected with avian and human influenza; however, the features that restrict influenza reassortment in swine and human hosts are not fully understood. Type I and III interferons (IFNs) act as the first line of defense against influenza virus infection of respiratory epithelium. To determine if human and swine have different capacities to mount an antiviral response the expression of IFN and IFN-stimulated genes (ISG) in normal human bronchial epithelial (NHBE) cells and normal swine bronchial epithelial (NSBE) cells was evaluated following infection with human (H3N2), swine (H1N1), and avian (H5N3, H5N2, H5N1) influenza A viruses. Expression of IFNλ and ISGs were substantially higher in NHBE cells compared to NSBE cells following H5 avian influenza virus infection compared to human or swine influenza virus infection. This effect was associated with reduced H5 avian influenza virus replication in human cells at late times post infection. Further, RIG-I expression was lower in NSBE cells compared to NHBE cells suggesting reduced virus sensing. Together, these studies identify key differences in the antiviral response between human and swine respiratory epithelium alluding to differences that may govern influenza reassortment

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Towards more sustainable and inclusive development corridors in Africa

Development corridors are linear programmes of infrastructure and agriculture aiming to facilitate rapid socio-economic development. In Africa, they are a major development activity, with 88 underway or planned corridors. Drawing from extensive literature and insights gleaned from a 4-year research programme, this review scrutinizes the impacts of development corridors on people, wildlife and ecosystems in Kenya and Tanzania, proposing solutions to achieve better outcomes. The overarching goal was to discern the principle challenges emerging from the practical execution of the prevailing corridor model. The holistic approach taken, assessing the development corridors paradigm through an integrated ecological, social, and economic lens, provides novel insights that have not been possible using more traditional – siloed – research approaches. Eight key challenge areas are identified: impact assessments processes; coherence across international, national and local planning; governance; inclusivity; equality; impacts on biodiversity and ecosystem services; incorporation of future climate risks; and integrated water resource management. Poorly planned and implemented corridors detrimentally impact livelihoods and ecosystems. They lack a sustainable development vision, detailed social, environmental or climate risk assessments, and develop incrementally in policy and corporate spaces. There is also often a disconnect between investors and recipient governments, with some investors funding what governments request without applying internationally-recognised safeguards, and governments lacking capacity and resources to enforce regulations. We make recommendations for addressing these challenge areas. These aim to enhance impact assessment efficacy; integrate local perspectives into effective and inclusive corridor planning; overcome siloed project development and implementation; anticipate future development projections; and prioritise landscape preservation for enhanced ecosystem services and climate resilience

Conformational Reorganization of the SARS Coronavirus Spike Following Receptor Binding: Implications for Membrane Fusion

The SARS coronavirus (SARS-CoV) spike is the largest known viral spike molecule, and shares a similar function with all class 1 viral fusion proteins. Previous structural studies of membrane fusion proteins have largely used crystallography of static molecular fragments, in isolation of their transmembrane domains. In this study we have produced purified, irradiated SARS-CoV virions that retain their morphology, and are fusogenic in cell culture. We used cryo-electron microscopy and image processing to investigate conformational changes that occur in the entire spike of intact virions when they bind to the viral receptor, angiotensin-converting enzyme 2 (ACE2). We have shown that ACE2 binding results in structural changes that appear to be the initial step in viral membrane fusion, and precisely localized the receptor-binding and fusion core domains within the entire spike. Furthermore, our results show that receptor binding and subsequent membrane fusion are distinct steps, and that each spike can bind up to three ACE2 molecules. The SARS-CoV spike provides an ideal model system to study receptor binding and membrane fusion in the native state, employing cryo-electron microscopy and single-particle image analysis

DreamTel; Diabetes risk evaluation and management tele-monitoring study protocol

<p>Abstract</p> <p>Background</p> <p>The rising prevalence of type 2 diabetes underlines the importance of secondary strategies for the prevention of target organ damage. While access to diabetes education centers and diabetes intensification management has been shown to improve blood glucose control, these services are not available to all that require them, particularly in rural and northern areas. The provision of these services through the Home Care team is an advance that can overcome these barriers. Transfer of blood glucose data electronically from the home to the health care provider may improve diabetes management.</p> <p>Methods and design</p> <p>The study population will consist of patients with type 2 diabetes with uncontrolled A1c levels living on reserve in the Battlefords region of Saskatchewan, Canada. This pilot study will take place over three phases. In the first phase over three months the impact of the introduction of the Bluetooth enabled glucose monitor will be assessed. In the second phase over three months, the development of guidelines based treatment algorithms for diabetes intensification will be completed. In the third phase lasting 18 months, study subjects will have diabetes intensification according to the algorithms developed.</p> <p>Discussion</p> <p>The first phase will determine if the use of the Bluetooth enabled blood glucose devices which can transmit results electronically will lead to changes in A1c levels. It will also determine the feasibility of recruiting subjects to use this technology. The rest of the Diabetes Risk Evaluation and Management Tele-monitoring (DreamTel) study will determine if the delivery of a diabetes intensification management program by the Home Care team supported by the Bluetooth enabled glucose meters leads to improvements in diabetes management.</p> <p>Trial Registration</p> <p>Protocol NCT00325624</p