Metagenomic evidence for a polymicrobial signature of sepsis

Our understanding of the host component of sepsis has made significant progress. However, detailed study of the microorganisms causing sepsis, either as single pathogens or microbial assemblages, has received far less attention. Metagenomic data offer opportunities to characterize the microbial communities found in septic and healthy individuals. In this study we apply gradient-boosted tree classifiers and a novel computational decontamination technique built upon SHapley Additive exPlanations (SHAP) to identify microbial hallmarks which discriminate blood metagenomic samples of septic patients from that of healthy individuals. Classifiers had high performance when using the read assignments to microbial genera [area under the receiver operating characteristic (AUROC=0.995)], including after removal of species ‘culture-confirmed’ as the cause of sepsis through clinical testing (AUROC=0.915). Models trained on single genera were inferior to those employing a polymicrobial model and we identified multiple co-occurring bacterial genera absent from healthy controls. While prevailing diagnostic paradigms seek to identify single pathogens, our results point to the involvement of a polymicrobial community in sepsis. We demonstrate the importance of the microbial component in characterising sepsis, which may offer new biological insights into the aetiology of sepsis, and ultimately support the development of clinical diagnostic or even prognostic tools.

Photochromic supramolecular photonic crystal based on host-guest interactions

A novel photo-responsive supramolecular hydrogel inverse opal material was described in this communication. The inverse opal material contains a host component β-cyclodextrin (β-CD) and a guest component 3-(acryloyl)amino-1,1',5,5'-tetramethoxyazobenzen (MAzo). Trans-MAzo...

Metagenomic evidence for a polymicrobial signature of sepsis

Our understanding of the host component of sepsis has made significant progress. However, detailed study of the microorganisms causing sepsis, either as single pathogens or microbial assemblages, has received far less attention. Metagenomic data offer opportunities to characterise the microbial communities found in septic and healthy individuals. In this study we apply gradient-boosted tree classifiers and a novel computational decontamination technique built upon SHapley Additive exPlanations (SHAP) to identify microbial hallmarks which discriminate blood metagenomic samples of septic patients from that of healthy individuals. Classifiers had high performance when using the read assignments to microbial genera (AUROC = 0.995), including after removal of species ‘confirmed’ as the cause of sepsis through clinical testing (AUROC = 0.915). Models trained on single genera were inferior to those employing a polymicrobial model and we identified multiple co-occurring bacterial genera absent from healthy controls.ImportanceWhile prevailing diagnostic paradigms seek to identify single pathogens, our results point to the involvement of a polymicrobial community in sepsis. We demonstrate the importance of the microbial component in characterising sepsis, which may offer new biological insights into the aetiology of sepsis and allow the development of clinical diagnostic or even prognostic tools.

A supramolecular photonic crystal hydrogel based on host–guest interactions for organic molecule recognition

The host component β-cyclodextrin (β-CD) and the guest component tertiary-butyl (t-Bu) were introduced into the polymeric backbone material of an inverse opal hydrogel.

The Nucleoprotein and Phosphoprotein Are Major Determinants of the Virulence of Viral Hemorrhagic Septicemia Virus in Rainbow Trout

ABSTRACTViral hemorrhagic septicemia virus (VHSV), a fish rhabdovirus, infects several marine and freshwater fish species. There are many strains of VHSV that affect different fish, but some strains of one genetic subgroup have gained high virulence in rainbow trout (Oncorhynchus mykiss). To define the genetic basis of high virulence in trout, we used reverse genetics to create chimeric VHSVs in which viral nucleoprotein (N), P (phosphoprotein), or M (matrix protein) genes, or the N and P genes, were exchanged between a trout-virulent European VHSV strain (DK-3592B) and a trout-avirulent North American VHSV strain (MI03). Testing of the chimeric recombinant VHSV (rVHSV) by intraperitoneal injection in juvenile rainbow trout showed that exchanges of the viral P or M genes had no effect on the trout virulence phenotype of either parental strain. However, reciprocal exchanges of the viral N gene resulted in a partial gain of function in the chimeric trout-avirulent strain (22% mortality) and complete loss of virulence for the chimeric trout-virulent strain (2% mortality). Reciprocal exchanges of both the N and P genes together resulted in complete gain of function in the chimeric avirulent strain (82% mortality), again with complete loss of virulence in the chimeric trout-virulent strain (0% mortality). Thus, the VHSV N gene contains an essential determinant of trout virulence that is strongly enhanced by the viral P gene. We hypothesize that the host-specific virulence mechanism may involve increased efficiency of the viral polymerase complex when the N and P proteins have adapted to more efficient interaction with a host component from rainbow trout.IMPORTANCERainbow trout farming is a major food source industry worldwide that has suffered great economic losses due to host jumps of fish rhabdovirus pathogens, followed by evolution of dramatic increases in trout-specific virulence. However, the genetic determinants of host jumps and increased virulence in rainbow trout are unknown for any fish rhabdovirus. Previous attempts to identify the viral genes containing trout virulence determinants of viral hemorrhagic septicemia virus (VHSV) have not been successful. We show here that, somewhat surprisingly, the viral nucleocapsid (N) and phosphoprotein (P) genes together contain the determinants responsible for trout virulence in VHSV. This suggests a novel host-specific virulence mechanism involving the viral polymerase and a host component. This differs from the known virulence mechanisms of mammalian rhabdoviruses based on the viral P or M (matrix) protein.

Supply Chain Hardware Integrity for Electronics Defense (SHIELD) Using Small “Dielets”

Under the DARPA/MTO SHIELD program, a Northrop Grumman led team is developing a supply chain traceability and authentication method to protect against the growing threat of counterfeit electronic parts. The foundation of our SHIELD solution is an advanced 100μm × 100μm × 20μm near-field RFID “dielet” fabricated on 14nm CMOS. This dielet will be embedded in a host component's packaging and provides a hardware root-of-trust through the integration of advanced key protection and cryptographic techniques. Throughout the life-cycle of the host component, the authenticity can be verified using an RF probe to energize and communicate with the dielet, performing a cryptographic challenge and providing a response to a centralized secure server and SHIELD authenticity database. This paper provides a general overview of the dielet design, packaging, and host component insertion. This research was developed with funding from the DARPA. The views, opinions and/or findings expressed are those of the author and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government.

Influences of Size and Amount of Colloidal Template and Droplet Diameter on the Formation of Porous-structured Hyaluronic Acid Particles

Combination of spray drying and templating method has been reported as one of the best method to produce porous pharmaceutical particles. However, current development reports have shown successful formation of porous particles with improper information on what mechanism occurs during the synthesis process and what process parameters involve the creation of particles with controllable pore structures and morphologies. In this report, influences of spray-drying parameters (i.e., size and amount of colloidal template, and droplet diameter) on porous particle fabrication were investigated. Hyaluronic acid (as a model of pharmaceutical drug host component) and polystyrene spheres (as a model of template) were used. The experimental results showed that the spray-drying parameters strongly influenced the external morphology (i.e., spherical and doughnut-shaped), particle outer diameter (from 300 to 2000 nm), and porous configuration (i.e., number of hole cavities and pore sizes (from 100 to 300 nm)) of particles. To qualitatively explain our synthesis strategies to get porous structure, the proposal of the particle formation mechanism was added.

Structural behavior of organic zeolites on guest sorption/desorption

The term organic zeolites, originally has been introduced to chemical literature by R.M. Barrer, to describe molecular crystals having open porous structures, able to reversibly absorb and desorb organic species with relatively weak, if any, sorption of water or other hydrophilic molecules. A characteristic feature of the organic zeolite structures, when compared to classical `inorganic' zeolites based on aluminosilicates, is the relatively weak intermolecular bonding within the host component. This is the reason for significant flexibility of the host crystal structure which changes its parameters upon guest absorption, desorption or exchange. The most characteristic property in this respect is absorption with `adsorbate generated sorption sites' which is the basis for design and control of selectivity and efficiency of sorption-desorption processes. In general, organic zeolite behavior may be observed on a large variety of supramolecular materials, including solvates of macrocyclic compounds and in the very important, so-called- MOFs. In the paper solvation of cyclodextrins and their complexes will be used as the convenient example, based on brand new, mostly yet unpublished large structures of heavily solvated cyclodextrin complexes in the solid state. Cyclodextrins are commonly known as materials having intra-molecular cavity able to accommodate guest species. This property, when combined with sorption in the inter-molecular space in the solid state structures of CDs leads to very interesting structures and properties. In general, such behavior may be observed only when CD moieties are at equilibrium with a solution of the respective guest and solvent species. The equilibria are quite sensitive to minor changes of solution chemical composition what may be observed microscopically as morphology changes of the crystalline phases. This phenomenon will be illustrated with short movies demonstrating crystal behavior on change of its environment. Novel x-ray structures will also be demonstrated and commented. This work was supported by grant POIG.01.01.02-14-102/09.

Yellowish-Brown Pigment with High near Infrared Reflective

Yellowish-brown inorganic pigments having a high near infrared solar reflectance have been synthesized. In this research, Fe2O3 was used as the host component, whereas, the mixtures of Sb2O3, SiO2, Al2O3, and TiO2 were used as the guest components. The guest components were investigated over a range of 36 different compositions. The results showed that the pigment, denoted by YB32, with a composition of Fe2O3, Sb2O3, SiO2, Al2O3, and TiO2 of 65, 15, 10, 2 and 8 wt.% respectively, generated a maximum near infrared solar reflectance of 40.8% while the YB3 pigment was found to have a minimum reflectance of 29.3%. The CIE L*a*b* colour index was used to measure the yellowish-brown pigment colours. The YB32 and YB3 pigment powders were also characterized by powder X-ray diffraction technique. It was found that the YB3 powder developed a new phase, FeSb2O3, which is mainly responsible for the decrease in the near infrared solar reflectance.

Performance of Near-Infrared Reflective Tile Roofs

A green pigments based on a Cr2O3-Al2O3-V2O5-TiO2composition have been synthesized and the ability of these pigments used with ceramic glazes to confer high solar reflectance has also been studied. Cr2O3is the host component and the adding mixtures of Al2O3, V2O5and TiO2as the guest components. The composition denoted by T1 composes of Cr2O3, TiO2, Al2O3and V2O5are 80, 4, 14 and 2 wt%, respectively, gives near infrared solar reflectance of 82.8%. T1 green pigments were prepared for ceramic cool tile roofs (denoted by T1 cool roof). The comparison study on the effectiveness of T1 ceramic cool roofs and a commercial ceramic cool tile roofs (denoted by C cool roof) show that the T1 cool roof has given a better result by keeping the tested room about 4 °C cooler.