Innate recognition of apoptotic cells:novel apoptotic cell-associated molecular patterns revealed by crossreactivity of anti-LPS antibodies

Cells dying by apoptosis are normally cleared by phagocytes through mechanisms that can suppress inflammation and immunity. Molecules of the innate immune system, the pattern recognition receptors (PRRs), are able to interact not only with conserved structures on microbes (pathogen-associated molecular patterns, PAMPs) but also with ligands displayed by apoptotic cells. We reasoned that PRRs might therefore interact with structures on apoptotic cells-apoptotic cell-associated molecular patterns (ACAMPs)-that are analogous to PAMPs. Here we show that certain monoclonal antibodies raised against the prototypic PAMP, lipopolysaccharide (LPS), can crossreact with apoptotic cells. We demonstrate that one such antibody interacts with a constitutively expressed intracellular protein, laminin-binding protein, which translocates to the cell surface during apoptosis and can interact with cells expressing the prototypic PRR, mCD14 as well as with CD14-negative cells. Anti-LPS cross reactive epitopes on apoptotic cells colocalised with annexin V-and C1q-binding sites on vesicular regions of apoptotic cell surfaces and were released associated with apoptotic cell-derived microvesicles (MVs). These results confirm that apoptotic cells and microbes can interact with the immune system through common elements and suggest that anti-PAMP antibodies could be used strategically to characterise novel ACAMPs associated not only with apoptotic cells but also with derived MVs

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Simulated Dielectric Characteristics of Pt/BST/Ni-Fe/Cu Multilayer Capacitor Stack for Storage Application

In this simulation research work, the metal-composite-metal (MCM) multilayer capacitor structure [Pt/BST/Ni-Fe/Cu] is proposed with Barium Strontium Titanate (BST) oxide material as the capacitor dielectric material for DRAM with permalloy Nickel-Ferrous (Ni-Fe) coated Copper (Cu) as the bottom conducting electrode and platinum as the top conducting electrode. This proposed MCM consists of 120 pin Cu bottom contact material, a I pm of Ni-Fe alloy over the stoichiometric composition of the BST oxide dielectric material of thickness 40 nm and dielectric constant of 775. The MCM structure is expected to deliver a maximum charge storage capacity of 109.75 fF for a capacitor in DRAM cell area of 0.64 mu m(2) well above the minimum requirement for DRAM cell. The leakage current density for a variation of voltage from 0 to 10 V has been simulated for temperature variation. When compared with the previous report, the proposed multi layer capacitor (MLC) structure shows promising potentials in terms of dielectric characteristics

Rapid Crystallization by Microwave Heating for Barium Strontium Titanate Powders Prepared using Slow-Rate Sol-Gel Technique

In this research work, different compositional ratios of Barium Strontium Titanate [BST] powders have been prepared using slow-rate gellification by sol-gell route and ex-situ microwave heating method. The finely grinded powders prepared were analyzed using Thermo Gravity Analysis [TGA], Differential Thermal Analysis [DTA] and characterized by X-ray Diffractometer [XRD]. TGA result shows that the organic solvents and unwanted impurities were removed at 117.89 degrees C and decomposition of carbonate took place at 205.19 degrees C. In addition, the material for 0.5 M ratio of Barium acetate and Strontium acetate and I M of Titanium Iso-propoxide started crystallization at 438.93 degrees C to yield BST. From the DTA results, it was found that when the microwave heating time was increased from 10 minutes to 25 minutes, the temperature at which endothermic reaction occurs has been shifted to lower values from 110 degrees C to 83.413 degrees C. These values matched those of the TGA results. The crystalline size was estimated from FWHM result to be in the range of 70 nanometer. The major peaks in the XRD analysis of the sample correspond to (100), (110), (111) and (200) were obtained for BST and agreed with American Standard for Test Measurement [ASTM] data. The materials exhibited pollycrystalline pattern with "d" values that matched with standard reports

Particle Size Analysis of Barium Titanate Powder by Slow-Rate Sol-Gel Process Route

In this research work, different compositional ratios of Barium Titanate [BT] powders have been prepared using slow-rate gellification by sol-gel route. The as-prepared materials have been calcinated at 300 degrees C for 8 hours to remove the presence of carbon, and subsequently annealed at 700 degrees C for one hour for the phase formation. After annealing, the finely grinded powders were characterized by X-Ray diffractometer [XRD], Atomic Force Microscope [AFM] and Nano particle size analyzer [NPSA]. The XRD pattern shows that the material was BT with polycrystalline phase. It exhibited tetragonal phase with crystalline size in the range of 97 nm. The lattice constants 'a' and 'c' were perfectly matched with the standard reports. The surface morphology study by AFM shows that the materials were homogenously fine grains. The average particle sizes reduce from 750 urn to 78.49 nm when the concentration of barium salt decreases. This observation clearly indicates that the tuning of the particle sizes is possible by controlling the compositional ratios of barium and titanium. The particle distributions of the samples have also been analyzed by nano particle size analyzer. In this work, samples with equal amount of barium and titanium exhibited particle size distribution down to 100 urn range, with good structural and morphological properties