Identifying immunological biomarkers of sepsis using cytometry bioinformatics and machine learning

Sepsis is a leading cause of mortality and significantly strains healthcare systems worldwide. Improving sepsis care and outcomes depends on appropriate risk stratification and timely identification of the causative pathogen to guide patient management and treatment. Enormous efforts have been made to identify diagnostic and prognostic biomarkers to aid decision making, but to date, they have failed to identify candidates with acceptable accuracy and precision to have an impact in the clinic. Past studies have often focused on individual biomarkers without considering the potential benefit of multi-marker panels incorporating deep immunological phenotyping. This work addressed this issue with a cross-disciplinary approach that integrated sepsis biomarker discovery, cytometry bioinformatics, and supervised machine learning. Firstly, a novel framework for cytometry data analysis was developed, along with a new ensemble clustering algorithm that reduced the risk of biasing exploratory analyses with the application of a single clustering technique. Secondly, the analysis framework was applied to a study cohort of severe sepsis patients, and their early immunological profile consisting of cellular and humoral parameters (within 36 hours of diagnosis) was determined. The captured immunological parameters were then combined with routine clinical data and lipid plasma concentrations to generate interpretable machine learning models for predicting mortality and the underlying cause of infection. The generated models discriminated between survivors and non-survivors, and between Gram-negative and Gram-positive infections, and identified potential combinations of biomarkers with predictive value

Three-Dimensional Nanostructured Palladium with Single Diamond Architecture for Enhanced Catalytic Activity

Fuel cells are a key new green technology that have applications in both transport and portable power generation. Carbon-supported platinum (Pt) is used as an anode and cathode electrocatalyst in low-temperature fuel cells fueled with hydrogen or low-molecular-weight alcohols. The cost of Pt and the limited world supply are significant barriers to the widespread use of these types of fuel cells. Comparatively, palladium has a 3 times higher abundance in the Earth’s crust. Here, a facile, low-temperature, and scalable synthetic route toward three-dimensional nanostructured palladium (Pd) employing electrochemical templating from inverse lyotropic lipid phases is presented. The obtained single diamond morphology Pd nanostructures exhibited excellent catalytic activity and stability toward methanol, ethanol, and glycerol oxidation compared to commercial Pd black, and the nanostructure was verified by small-angle X-ray scattering, scanning tunneling electron microscopy, and cyclic voltammetry

The lifetime of charged dust in the atmosphere

8 pagesWind-blown dust plays a critical role in numerous geophysical and biological systems, yet current models fail to explain the transport of coarse-mode particles (>5μm) to great distances from their sources. For particles larger than a few microns, electrostatic effects have been invoked to account for longer-than-predicted atmospheric residence times. Although much effort has focused on elucidating the charging processes, comparatively little effort has been expended understanding the stability of charge on particles once electrified. Overall, electrostatic-driven transport requires that charge remain present on particles for days to weeks. Here,we present a set of experiments designed to explore the longevity of electrostatic charge on levitated airborne particles after a single charging event. Using an acoustic levitator,we measured the charge on particles of different material compositions suspended in atmospheric conditions for long periods of time. In dry environments, the total charge on particles decayed in over 1week. The decay timescale decreased to days in humid environments. These results were independent of particle material and charge polarity. However, exposure to UV radiation could both increase and decrease the decay time depending on polarity. Our work suggests that the rate of charge decay on airborne particles is solely determined by ion capture from the air. Furthermore, using a one-dimensional sedimentation model, we predict that atmospheric dust of order 10μm will experience the largest change in residence time due to electrostatic forces

The microRNA‑200 family acts as an oncogene in colorectal cancer by inhibiting the tumor suppressor RASSF2

This study aimed to determine whether manipulation of the microRNA‑200 (miR‑200) family could influence colon adenocarcinoma cell behavior. The miR‑200 family has a significant role in tumor suppression and functions as an oncogene. In vitro studies on gain and loss of function with small interfering RNA demonstrated that the miR‑200 family could regulate RASSF2 expression. Knockdown of the miR‑200 family in the HT‑29 colon cancer cell line increased KRAS expression but decreased signaling in the MAPK/ERK signaling pathway through reduced ERK phosphorylation. Increased expression of the miR‑200 family in the CCD‑841 colon epithelium cell line increased KRAS expression and led to increased signaling in the MAPK/ERK signaling pathway but increased ERK phosphorylation. Functionally, knockdown of the miR‑200 family led to decreased cell proliferation in the HT‑29 cells; therefore, increased miR‑200 family expression could increase cell proliferation in the CCD‑841 cell line. The present study included a large paired miR array dataset (n=632), in which the miR‑200 family was significantly found to be increased in colon cancer when compared with normal adjacent colon epithelium. In a miR‑seq dataset (n=199), the study found that miR‑200 family expression was increased in localized colon cancer compared with metastatic disease. Decreased expression was associated with poorer overall survival. The miR‑200 family directly targeted RASSF2 and was inversely correlated with RASSF2 expression (n=199, all P<0.001). Despite the well‑defined role of the miR‑200 family in tumor suppression, the present findings demonstrated a novel function of the miR‑200 family in tumor proliferation

Conferencing the international at the World Pacifist Meeting in India, 1949

This paper considers how the act of conferencing was central to imagining, negotiating and contesting post-war pacifism as an internationalist project. The paper contends that internationalism and the international conference are inexorably entwined. Through studying the conference geographers can explore the situated historical and political geographies of internationalism which belies its otherwise transcendent or universalist claims. A reading of the 1949 World Pacifist Meeting in India is used to make two key arguments. Firstly, it shows how conferences operate as stage-managed events through which to script and perform an alternative vision of internationalism. Half conference, half pilgrimage, the global composition of delegates was arranged to suggest a space ‘singularly free from any sense of geographical limitation’. Yet total immersion in the rich cultural and historical context of India marked an uneven internationalist arena, where the ‘Land of Gandhi’ was held with unparalleled revere. Secondly, whilst geographers and others have turned to conferencing in recent years, this has largely been contained to ‘summitry’ and high-end diplomacy. This paper calls for geographers to consider a wider range of conferencing spaces and practices, and argues that studying ‘other conferences’ by necessity opens up consideration of other forms of internationalism. The paper concludes that the World Pacifist Meeting’s delegates imagined an alternative form of internationalism, exemplified by an alternative form of international conference, which sought to challenge state-centric readings of global power relations

Cellular senescence in osteoarthritis pathology

Cellular senescence is a state of stable proliferation arrest of cells. The senescence pathway has many beneficial effects and is seen to be activated in damaged/stressed cells, as well as during embryonic development and wound healing. However, the persistence and accumulation of senescent cells in various tissues can also impair function and have been implicated in the pathogenesis of many age‐related diseases. Osteoarthritis (OA), a severely debilitating chronic condition characterized by progressive tissue remodeling and loss of joint function, is the most prevalent disease of the synovial joints, and increasing age is the primary OA risk factor. The profile of inflammatory and catabolic mediators present during the pathogenesis of OA is strikingly similar to the secretory profile observed in ‘classical’ senescent cells. During OA, chondrocytes (the sole cell type present within articular cartilage) exhibit increased levels of various senescence markers, such as senescence‐associated beta‐galactosidase (SAβGal) activity, telomere attrition, and accumulation of p16ink4a. This suggests the hypothesis that senescence of cells within joint tissues may play a pathological role in the causation of OA. In this review, we discuss the mechanisms by which senescent cells may predispose synovial joints to the development and/or progression of OA, as well as touching upon various epigenetic alterations associated with both OA and senescence