Neutrophils in Tuberculosis: Cell Biology,Cellular Networking and Multitasking in Host Defense

Neutrophils readily infiltrate infection foci, phagocytose and usually destroy microbes. In tuberculosis (TB), a chronic pulmonary infection caused by Mycobacterium tuberculosis (Mtb), neutrophils harbor bacilli, are abundant in tissue lesions, and their abundances in blood correlate with poor disease outcomes in patients. The biology of these innate immune cells in TB is complex. Neutrophils have been assigned host-beneficial as well as deleterious roles. The short lifespan of neutrophils purified from blood poses challenges to cell biology studies, leaving intracellular biological processes and the precise consequences of Mtb–neutrophil interactions ill-defined. The phenotypic heterogeneity of neutrophils, and their propensity to engage in cellular cross-talk and to exert various functions during homeostasis and disease, have recently been reported, and such observations are newly emerging in TB. Here, we review the interactions of neutrophils with Mtb, including subcellular events and cell fate upon infection, and summarize the cross-talks between neutrophils and lung-residing and -recruited cells. We highlight the roles of neutrophils in TB pathophysiology, discussing recent findings from distinct models of pulmonary TB, and emphasize technical advances that could facilitate the discovery of novel neutrophil-related disease mechanisms and enrich our knowledge of TB pathogenesis.     

Compressive properties of pristine and SiC-Te-added MgB2 powders,green compacts and spark-plasma-sintered bulks

Pristine and (SiC+Te)-added MgB₂ powders, green and spark plasma sintered (SPS) compacts were investigated from the viewpoint of quasi-static and dynamic (Split-Hopkinson Pressure Bar, SHPB) compressive mechanical properties The amount of the additive (SiC+Te) was selected to be the optimum one for maximization of the superconducting functional parameters. Pristine and added MgB₂ show very similar compressive parameters (tan δ, fracture strength, Vickers hardness, others) and fragment size in the SHPB test. However, for the bulk SPSed samples the ratio of intergranular to transgranular fracturing changes, the first one being stronger in the added sample. This is reflected in the quasi-static K_IC that is higher for the added sample. Despite this result, sintered samples are brittle and have roughly similar fragmentation behavior as for brittle engineering ceramics. In the fragmentation process, the composite nature of our samples should be considered with a special focus on MgB₂ blocks (colonies) that show the major contribution to fracturing. The Glenn-Chudnovsky model of fracturing under dynamic load provides the closest values to our experimental fragment size data.     

Interplay between Humoral and CLA+ T Cell Response against Candida albicans in Psoriasis

Candida albicans (CA) infections have been associated with psoriasis onset or disease flares. However, the integrated immune response against this fungus is still poorly characterized in psoriasis. We studied specific immunoglobulins in plasma and the CA response in cocultures of circulating memory CD45RA⁻ cutaneous lymphocyte antigen (CLA)^+/− T cell with autologous epidermal cells from plaque and guttate psoriasis patients (cohort 1, n = 52), and also healthy individuals (n = 17). A complete proteomic profile was also evaluated in plaque psoriasis patients (cohort 2, n = 114) regarding their anti-CA IgA levels. Increased anti-CA IgA and IgG levels are present in the plasma from plaque but not guttate psoriasis compared to healthy controls. CA cellular response is confined to CLA⁺ T cells and is primarily Th17. The levels of anti-CA IgA are directly associated with CLA⁺ Th17 response in plaque psoriasis. Proteomic analysis revealed distinct profiles in psoriasis patients with high anti-CA IgA. C-C motif chemokine ligand 18, chitinase-3-like protein 1 and azurocidin were significantly elevated in the plasma from plaque psoriasis patients with high anti-CA levels and severe disease. Our results indicate a mechanism by which Candida albicans exposure can trigger a clinically relevant IL-17 response in psoriasis. Assessing anti-CA IgA levels may be useful in order to evaluate chronic psoriasis patients.     

Enzymatic degradation of thermoresponsive poly(N‐isopropylacrylamide) grafted to carboxymethylcellulose copolymers

The enzymatic degradation of poly(N‐isopropyl acrylamide) (PNIPAM) grafted to carboxymethylcellulose (CMC) copolymers with a cellulasic preparation (Trichoderma viride) was studied. The enzymatic activity of the cellulasic preparation against CMC and the grafted copolymers was determined by the Petterson–Porath method, while their reduced viscosity variation in the presence of the same preparation was also followed. It has been shown that the enzymatic degradation behavior depends on the copolymer composition and the reaction temperature. Reducing sugars analysis showed that the experimental values for the grafted copolymers were higher than the calculated ones. At 50°C, the enzymatic reaction is completed in about 20 min for the copolymers, whereas for CMC it takes more than 40 min. It can be concluded that their enzymatic degradation is facilitated by the presence of the PNIPAM grafts. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1383–1386, 2003     

Evaluation of hydrogen bonding ability of liquids and solids by C-13 NMR. Silica gel as a strong hydrogen bond donor

The chemical shift difference between signals of C() and C() of unsaturated ketones, , which we used before to measure acid strengths, has now been used to evaluate the hydrogen bond donor ability of solvents which are not acidic enough to hydronate the indicator. For such solvents there is no general correlation between H-bond donor ability and acid strength: hexa-fluoroisopropanol is a much weaker acid than acetic acid, but it is a stronger H-bond donor. The method can be applied to evaluate the H-bonding properties of solid surfaces, and it was thus found that silica gel has a much stronger H-bond donor ability than methanol or acetic acid.     

Metallic Conductive Nanowires Elaborated by PVD Metal Deposition on Suspended DNA Bundles

Metallic conductive nanowires (NWs) with DNA bundle core are achieved, thanks to an original process relying on double‐stranded DNA alignment and physical vapor deposition (PVD) metallization steps involving a silicon substrate. First, bundles of DNA are suspended with a repeatable process between 2 µm high parallel electrodes with separating gaps ranging from 800 nm to 2 µm. The process consists in the drop deposition of a DNA lambda‐phage solution on the electrodes followed by a naturally evaporation step. The deposition process is controlled by the DNA concentration within the buffer solution, the drop volume, and the electrode hydrophobicity. The suspended bundles are finally metallized with various thicknesses of titanium and gold by a PVD e‐beam evaporation process. The achieved NWs have a width ranging from a few nanometers up to 100 nm. The electrical behavior of the achieved 60 and 80 nm width metallic NWs is shown to be Ohmic and their intrinsic resistance is estimated according to different geometrical models of the NW section area. For the 80 nm width NWs, a resistance of about few ohms is established, opening exploration fields for applications in microelectronics.     

Characterization of microdevices for ferrous chloride separation for biosensing applications

Ferrous chloride has a variety of applications such as a reducing flocculation agent in waste-water treatment, especially for wastes containing chromate, in the laboratory synthesis of iron complexes and it is employed as a reducing agent in many organic syntheses. The device used for experiment was fabricated on the silicon wafer as support for two electrodes in a SU8 polymer microchannel with an inlet, for the injection of aqueous solution of ferrous chloride, and two outlets, for the two by-products of separated solutions. The various parameters of the device were measured by White Light Interferometer (WLI) and Scanning Electron Microscopy (SEM). The magnetic field created by applying different types of potential between two electrodes determined ferrous chloride to separate in ferrous oxide and chlorine (in gaseous form). If a protein is added in this solution we have the possibility to immobilize the protein on the iron particles and on the channel area. The electrical results were collected using a semiconductor system analyzer Keithley and were examined subsequently. The Fe complexes deposited on the electrodes were characterized by XRD analyses.     

An Architecture for Human‐Guided Autonomy: Team TROOPER at the DARPA Robotics Challenge Finals

Recent robotics efforts have automated simple, repetitive tasks to increase execution speed and lessen an operator's cognitive load, allowing them to focus on higher‐level objectives. However, an autonomous system will eventually encounter something unexpected, and if this exceeds the tolerance of automated solutions, there must be a way to fall back to teleoperation. Our solution is a largely autonomous system with the ability to determine when it is necessary to ask a human operator for guidance. We call this approach human‐guided autonomy. Our design emphasizes human‐on‐the‐loop control where an operator expresses a desired high‐level goal for which the reasoning component assembles an appropriate chain of subtasks. We introduce our work in the context of the DARPA Robotics Challenge (DRC) Finals. We describe the software architecture Team TROOPER developed and used to control an Atlas humanoid robot. We employ perception, planning, and control automation for execution of subtasks. If subtasks fail, or if changing environmental conditions invalidate the planned subtasks, the system automatically generates a new task chain. The operator is able to intervene at any stage of execution, to provide input and adjustment to any control layer, enabling operator involvement to increase as confidence in automation decreases. We present our performance at the DRC Finals and a discussion about lessons learned.     

Verifying Temporal Properties of Reactive Systems: A STeP Tutorial

We review a number of formal verification techniques supported by STeP, the Stanford Temporal Prover, describing how the tool can be used to verify properties of several versions of the Bakery Mutual exclusion algorithm for mutual exclusion. We verify the classic two-process algorithm and simple variants, as well as an atomic parameterized version. The methods used include deductive verification rules, verification diagrams, automatic invariant generation, and finite-state model checking and abstraction.