Standardized Bronchoscopy Testing for Immunocompromised Patients

Aims for Improvement Determine the consistency in which the order set was followed Determine the length of time from finding pulmonary infiltrate to consultation Determine the length of time from consultation to bronchoscopy Determine whether a follow up note was written by pulmonary Determine whether management is affected based on obtained result

Surface superconducting states in a polycrystalline MgB2_{2} sample

We report results of dc magnetic and ac linear low-frequency study of a polycrystalline MgB$_2$ sample. AC susceptibility measurements at low frequencies, performed under dc fields parallel to the sample surface, provide a clear evidence for surface superconducting states in MgB$_2$.Comment: 4 pages and 5 figure

The internal magnetic field in superconducting ferromagnets

We have measured the nonlinear response to the ac magnetic field in the superconducting weak ferromagnet Ru-1222, at different regimes of sample cooling which provides unambiguous evidence of the interplay of the domain structure and the vorticity in the superconducting state. This is {\em direct} proof of coexistence of ferromagnetic and superconductive order parameters in high-$T_c$ ruthenocuprates.Comment: 9 pages, 6 figure

The low-frequency response in the surface superconducting state of ZrB12_{12} single crystal}

The large nonlinear response of a single crystal ZrB$_{12}$ to an ac field (frequency 40 - 2500 Hz) for $H_0>H_{c2}$ has been observed. Direct measurements of the ac wave form and the exact numerical solution of the Ginzburg-Landau equations, as well as phenomenological relaxation equation, permit the study of the surface superconducting states dynamics. It is shown, that the low frequency response is defined by transitions between the metastable superconducting states under the action of an ac field. The relaxation rate which determines such transitions dynamics, is found.Comment: 7 pages, 11 figure

Electromagnetic interference shielding in unmanned aerial vehicle against lightning strike

Electromagnetic interference (EMI) due to lightning strike in Unmanned Aerial Vehicle (UAV) became a critical issue, since it could cause a severe damaged to electronic equipment which was installed in UAV. This paper proposed a method to reduce EMI by creating shield over the body of UAV with aluminum foil with thickness 0.15mm. A standard lightning impulse-voltage generated by impulse generator was delivered to the high voltage (HV) electrode at a particular distance from UAV. Indirect effect of lightning strike was investigated by measuring induced voltage inside the compartment of UAV fuselage during flashover between the HV electrode and UAV. Flashover between the HV electrode and UAV simulated the lightning strike. The result showed that the highest voltage only 1V at UAV compartment when 150kV impulse voltage supplied to the electrode with striking area on the wing. The measured voltage was far below 100V as the insulation level of low voltage equipment inside UAV. Although the direct effect of lightning has created a burning hole on the surface aluminum foil with thickness 0.15mm, the effect was overcome by increasing the thickness to 0.3mm. The application of aluminum foil over the surface of UAV repelled the electromagnetic interference which acted as a Faraday cage. The shielding method was successfully reduced the effect of EMI

Parametric Amplification of Nonlinear Response of Single Crystal Niobium

Giant enhancement of the nonlinear response of a single crystal Nb sample, placed in {\it a pumping ac magnetic field}, has been observed experimentally. The experimentally observed amplitude of the output signal is about three orders of magnitude higher than that seen without parametric pumping. The theoretical analysis based on the extended double well potential model provides a qualitative explanation of the experimental results as well as new predictions of two bifurcations for specific values of the pumping signal.Comment: 6 pages, 10 figure

Mitochondrial ROS drive resistance to chemotherapy and immune-killing in hypoxic non-small cell lung cancer

BACKGROUND: Solid tumors subjected to intermittent hypoxia are characterized by resistance to chemotherapy and immune-killing by effector T-lymphocytes, particularly tumor-infiltrating Vγ9Vδ2 T-lymphocytes. The molecular circuitries determining this double resistance are not known. METHODS: We analyzed a panel of 28 human non-small cell lung cancer (NSCLC) lines, using an in vitro system simulating continuous and intermittent hypoxia. Chemosensitivity to cisplatin and docetaxel was evaluated by chemiluminescence, ex vivo Vγ9Vδ2 T-lymphocyte expansion and immune-killing by flow cytometry. Targeted transcriptomics identified efflux transporters and nuclear factors involved in this chemo-immuno-resistance. The molecular mechanism linking Hypoxia-inducible factor-1α (HIF-1α), CCAAT/Enhancer Binding Protein-β (C/EBP-β) isoforms LAP and LIP, ABCB1, ABCC1 and ABCA1 transporters were evaluated by immunoblotting, RT-PCR, RNA-IP, ChIP. Oxidative phosphorylation, mitochondrial ATP, ROS, depolarization, O(2) consumption were monitored by spectrophotometer and electronic sensors. The role of ROS/HIF-1α/LAP axis was validated in knocked-out or overexpressing cells, and in humanized (Hu-CD34(+)NSG) mice bearing LAP-overexpressing tumors. The clinical meaning of LAP was assessed in 60 NSCLC patients prospectively enrolled, treated with chemotherapy. RESULTS: By up-regulating ABCB1 and ABCC1, and down-regulating ABCA1, intermittent hypoxia induced a stronger chemo-immuno-resistance than continuous hypoxia in NSCLC cells. Intermittent hypoxia impaired the electron transport chain and reduced O(2) consumption, increasing mitochondrial ROS that favor the stabilization of C/EBP-β mRNA mediated by HIF-1α. HIF-1α/C/EBP-β mRNA binding increases the splicing of C/EBP-β toward the production of LAP isoform that transcriptionally induces ABCB1 and ABCC1, promoting the efflux of cisplatin and docetaxel. LAP also decreases ABCA1, limiting the efflux of isopentenyl pyrophosphate, i.e. the endogenous activator of Vγ9Vδ2 T-cells, and reducing the immune-killing. In NSCLC patients subjected to cisplatin-based chemotherapy, C/EBP-β LAP was abundant in hypoxic tumors and was associated with lower response to treatment and survival. LAP-overexpressing tumors in Hu-CD34(+)NSG mice recapitulated the patients’ chemo-immuno-resistant phenotype. Interestingly, the ROS scavenger mitoquinol chemo-immuno-sensitized immuno-xenografts, by disrupting the ROS/HIF-1α/LAP cascade. CONCLUSIONS: The impairment of mitochondrial metabolism induced by intermittent hypoxia increases the ROS-dependent stabilization of HIF-1α/LAP complex in NSCLC, producing chemo-immuno-resistance. Clinically used mitochondrial ROS scavengers may counteract such double resistance. Moreover, we suggest C/EBP-β LAP as a new predictive and prognostic factor in NSCLC patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-022-02447-6

Evaluating amplified rDNA restriction analysis assay for identification of bacterial communities

Amplified ribosomal DNA restriction analysis (ARDRA) and restriction fragment length polymorphism were originally used for strain typing and for screening clone libraries to identify phylogenetic clusters within a microbial community. Here we used ARDRA as a model to examine the capacity of restriction-based techniques for clone identification, and the possibility of deriving phylogenetic information from ARDRA-based dendrograms. ARDRA was performed in silico on 48,759 sequences from the Ribosomal Database Project, and it was found that the fragmentation profiles were not necessarily unique for each sequence in the database, resulting in different species sharing fragmentation profiles. Although ARDRA-based clusters separated clones into different genera, these phylogenetic clusters did not overlap with trees constructed according to sequence alignment, calling into question the intra-genus ARDRA-based phylogeny. It is thus suggested that the prediction power of ARDRA clusters in identifying clone phylogeny be regarded with caution

The microbiota regulates murine inflammatory responses to toxin-induced CNS demyelination but has minimal impact on remyelination.

The microbiota is now recognized as a key influence on the host immune response in the central nervous system (CNS). As such, there has been some progress toward therapies that modulate the microbiota with the aim of limiting immune-mediated demyelination, as occurs in multiple sclerosis. However, remyelination-the regeneration of myelin sheaths-also depends upon an immune response, and the effects that such interventions might have on remyelination have not yet been explored. Here, we show that the inflammatory response during CNS remyelination in mice is modulated by antibiotic or probiotic treatment, as well as in germ-free mice. We also explore the effect of these changes on oligodendrocyte progenitor cell differentiation, which is inhibited by antibiotics but unaffected by our other interventions. These results reveal that high combined doses of oral antibiotics impair oligodendrocyte progenitor cell responses during remyelination and further our understanding of how mammalian regeneration relates to the microbiota.This work was supported by grants from UK Multiple Sclerosis Society, The British Trust for the Myelin Project, MedImmune, The Adelson Medical Research Foundation, Wellcome Trust, BBSRC, the Leverhulme Trust and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute. CEM was supported by grants from the Jean Shanks Foundation and the James Baird Fund, AGF was supported by an ECTRIMS fellowship and OBZ received a BIRAX fellowship