357 research outputs found
A superconducting-nanowire 3-terminal electronic device
In existing superconducting electronic systems, Josephson junctions play a
central role in processing and transmitting small-amplitude electrical signals.
However, Josephson-junction-based devices have a number of limitations
including: (1) sensitivity to magnetic fields, (2) limited gain, (3) inability
to drive large impedances, and (4) difficulty in controlling the junction
critical current (which depends sensitively on sub-Angstrom-scale thickness
variation of the tunneling barrier). Here we present a nanowire-based
superconducting electronic device, which we call the nanocryotron (nTron), that
does not rely on Josephson junctions and can be patterned from a single thin
film of superconducting material with conventional electron-beam lithography.
The nTron is a 3-terminal, T-shaped planar device with a gain of ~20 that is
capable of driving impedances of more than 100 k{\Omega}, and operates in
typical ambient magnetic fields at temperatures of 4.2K. The device uses a
localized, Joule-heated hotspot formed in the gate to modulate current flow in
a perpendicular superconducting channel. We have characterized the nTron,
matched it to a theoretical framework, and applied it both as a digital logic
element in a half-adder circuit, and as a digital amplifier for superconducting
nanowire single-photon detectors pulses. The nTron has immediate applications
in classical and quantum communications, photon sensing and astronomy, and its
performance characteristics make it compatible with existing superconducting
technologies. Furthermore, because the hotspot effect occurs in all known
superconductors, we expect the design to be extensible to other materials,
providing a path to digital logic, switching, and amplification in
high-temperature superconductors
Quality of Life Changes Following Peripheral Blood Stem Cell Transplantation and Participation in a Mixed-Type, Moderate-intensity, Exercise Program
Summary:The purpose of this investigation was to evaluate the impact of undertaking peripheral blood stem cell transplantation (PBST) on quality of life (QoL), and to determine the effect of participating in a mixed-type, moderate-intensity exercise program on QoL. It was also an objective to determine the relationship between peak aerobic capacity and QoL in PBST patients. QoL was assessed via the CARES questionnaire and peak aerobic capacity by a maximal graded treadmill test, pretransplant (PI), post transplant (PII) and following a 12-week intervention period (PIII). At PII, 12 patients were divided equally into a control or exercise intervention group. Undergoing a PBST was associated with a statistically but not clinically significant decline in QoL (P<0.05). Following the intervention, exercising patients demonstrated an improved QoL when compared with pretransplant ratings (P<0.01) and nonexercising transplant patients (P<0.05). Moreover, peak aerobic capacity and QoL were correlated (P<0.05). The findings demonstrated that exercise participation following oncology treatment is associated with a reduction in the number and severity of endorsed problems, which in turn leads to improvements in global, physical and psychosocial QoL. Furthermore, a relationship between fitness and QoL exists, with those experiencing higher levels of fitness also demonstrating higher QoL.Bone Marrow Transplantation (2004) 33, 553-558. doi:10.1038/sj.bmt.1704378 Published online 12 January 200
The intrahepatic signalling niche of hedgehog is defined by primary cilia positive cells during chronic liver injury
Background & Aims: In vertebrates, canonical Hedgehog (Hh) pathway activation requires Smoothened (SMO) translocation to the primary cilium (Pc), followed by a GLI-mediated transcriptional response. In addition, a similar gene regulation occurs in response to growth factors/cytokines, although independently of SMO signalling. The Hh pathway plays a critical role in liver fibrosis/regeneration; however, the mechanism of activation in chronic liver injury is poorly understood. This study aimed to characterise Hh pathway activation upon thioacetamide (TAA)- induced chronic liver injury in vivo by defining Hh-responsive cells, namely cells harbouring Pc and Pc-localised SMO. Methods: C57BL/6 mice (wild-type or Ptc1+/_) were TAA-treated. Liver injury and Hh ligand/pathway mRNA and protein expression were assessed in vivo. SMO/GLI manipulation and SMO dependent/ independent activation of GLI-mediated transcriptional response in Pc-positive (Pc+) cells were studied in vitro. Results: In vivo, Hh activation was progressively induced following TAA. At the epithelial-mesenchymal interface, injured hepatocytes produced Hh ligands. Progenitors, myofibroblasts, leukocytes and hepatocytes were GLI2+. Pc+ cells increased following TAA, but only EpCAM+/GLI2+ progenitors were Pc+/SMO+. In vitro, SMO knockdown/hGli3-R overexpression reduced proliferation/viability in Pc+ progenitors, whilst increased proliferation occurred with hGli1 overexpression. HGF induced GLI transcriptional activity independently of Pc/SMO. Ptc1+/_ mice exhibited increased progenitor, myofibroblast and fibrosis responses. Conclusions: In chronic liver injury, Pc+ progenitors receive Hh ligand signals and process it through Pc/SMO-dependent activation of GLI-mediated transcriptional response. Pc/SMO-independent GLI activation likely occurs in Pc_/GLI2+ cells. Increased fibrosis in Hh gain-of-function mice likely occurs by primary progenitor expansion/proliferation and secondary fibrotic myofibroblast expansion, in close contact with progenitors
Cell migration leads to spatially distinct but clonally related airway cancer precursors
Background Squamous cell carcinoma of the lung is a common cancer with 95% mortality at 5 years. These cancers arise from preinvasive lesions, which have a natural history of development progressing through increasing severity of dysplasia to carcinoma in situ (CIS), and in some cases, ending in transformation to invasive carcinoma. Synchronous preinvasive lesions identified at autopsy have been previously shown to be clonally related. Methods Using autofluorescence bronchoscopy that allows visual observation of preinvasive lesions within the upper airways, together with molecular profiling of biopsies using gene sequencing and loss-of-heterozygosity analysis from both preinvasive lesions and from intervening normal tissue, we have monitored individual lesions longitudinally and documented their visual, histological and molecular relationship. Results We demonstrate that rather than forming a contiguous field of abnormal tissue, clonal CIS lesions can develop at multiple anatomically discrete sites over time. Further, we demonstrate that patients with CIS in the trachea have invariably had previous lesions that have migrated proximally, and in one case, into the other lung over a period of 12 years. Conclusions Molecular information from these unique biopsies provides for the first time evidence that field cancerisation of the upper airways can occur through cell migration rather than via local contiguous cellular expansion as previously thought. Our findings urge a clinical strategy of ablating high-grade premalignant airway lesions with subsequent attentive surveillance for recurrence in the bronchial tree
Assessment of Minimal Residual Disease in Standard-Risk AML
BACKGROUND: Despite the molecular heterogeneity of standard-risk acute myeloid leukemia (AML), treatment decisions are based on a limited number of molecular genetic markers and morphology-based assessment of remission. Sensitive detection of a leukemia-specific marker (e.g., a mutation in the gene encoding nucleophosmin [NPM1]) could improve prognostication by identifying submicroscopic disease during remission. METHODS: We used a reverse-transcriptase quantitative polymerase-chain-reaction assay to detect minimal residual disease in 2569 samples obtained from 346 patients with NPM1-mutated AML who had undergone intensive treatment in the National Cancer Research Institute AML17 trial. We used a custom 51-gene panel to perform targeted sequencing of 223 samples obtained at the time of diagnosis and 49 samples obtained at the time of relapse. Mutations associated with preleukemic clones were tracked by means of digital polymerase chain reaction. RESULTS: Molecular profiling highlighted the complexity of NPM1-mutated AML, with segregation of patients into more than 150 subgroups, thus precluding reliable outcome prediction. The determination of minimal-residual-disease status was more informative. Persistence of NPM1-mutated transcripts in blood was present in 15% of the patients after the second chemotherapy cycle and was associated with a greater risk of relapse after 3 years of follow-up than was an absence of such transcripts (82% vs. 30%; hazard ratio, 4.80; 95% confidence interval [CI], 2.95 to 7.80; P<0.001) and a lower rate of survival (24% vs. 75%; hazard ratio for death, 4.38; 95% CI, 2.57 to 7.47; P<0.001). The presence of minimal residual disease was the only independent prognostic factor for death in multivariate analysis (hazard ratio, 4.84; 95% CI, 2.57 to 9.15; P<0.001). These results were validated in an independent cohort. On sequential monitoring of minimal residual disease, relapse was reliably predicted by a rising level of NPM1-mutated transcripts. Although mutations associated with preleukemic clones remained detectable during ongoing remission after chemotherapy, NPM1 mutations were detected in 69 of 70 patients at the time of relapse and provided a better marker of disease status. CONCLUSIONS: The presence of minimal residual disease, as determined by quantitation of NPM1-mutated transcripts, provided powerful prognostic information independent of other risk factors. (Funded by Bloodwise and the National Institute for Health Research; Current Controlled Trials number, ISRCTN55675535.)
Production of highly-polarized positrons using polarized electrons at MeV energies
The Polarized Electrons for Polarized Positrons experiment at the injector of
the Continuous Electron Beam Accelerator Facility has demonstrated for the
first time the efficient transfer of polarization from electrons to positrons
produced by the polarized bremsstrahlung radiation induced by a polarized
electron beam in a high- target. Positron polarization up to 82\% have been
measured for an initial electron beam momentum of 8.19~MeV/, limited only by
the electron beam polarization. This technique extends polarized positron
capabilities from GeV to MeV electron beams, and opens access to polarized
positron beam physics to a wide community.Comment: 5 pages, 4 figure
First Results from The GlueX Experiment
The GlueX experiment at Jefferson Lab ran with its first commissioning beam
in late 2014 and the spring of 2015. Data were collected on both plastic and
liquid hydrogen targets, and much of the detector has been commissioned. All of
the detector systems are now performing at or near design specifications and
events are being fully reconstructed, including exclusive production of
, and mesons. Linearly-polarized photons were
successfully produced through coherent bremsstrahlung and polarization transfer
to the has been observed.Comment: 8 pages, 6 figures, Invited contribution to the Hadron 2015
Conference, Newport News VA, September 201
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