The article describes a system for the trackside detection of rail vehicles based on the fiber-optic interferometer. Besides the phase sensitive distributed systems, the interferometers are the only ...fiberoptic sensing technology capable of working in indirect contact with the rail while offering similar functionality as track-mounted sensors. The proposed trackside sensor uses the balanced Mach-Zehnder interferometer. The advantage of this type of interferometer is easy multiplexing, low cost and the possibility of flexible sensor design. The article describes the design of a sensor with multiple outputs of 3x3 coupler used for passive phase demodulation. The sensor has been tested on the railway track attached to the railway bridge. Results have shown that train operations can be reliably monitored using the developed system and it allows distinguishing the individual cars or wagon on the closer track.
WE HAVE LIFT OFF Hruby, David
Fire Chief,
03/2008, Letnik:
52, Številka:
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Trade Publication Article
Just plug it in and qualified technicians can use the Aquis software to perform upgrades, conduct diagnostics and monitor system functions in real-time on-site or remotely using an Internet ...connection.
In this commentary, we identify a phonics-first ideology and its polemical distortions of research and science to promote legislation that constrains and diminishes the teaching of reading. We affirm ...our own, and a majority of reading professionals’, commitment to teaching phonics. However, we argue that phonics instruction is more effective when embedded in a more comprehensive program of literacy instruction that accommodates students’ individual needs and multiple approaches to teaching phonics—a view supported by substantial research. After summarizing the politicization of phonics in the United States, we critique a legislated training course for teachers in Tennessee as representative of how a phonics-first ideology is expressed polemically for political purposes. We contrast it with a more collaboratively developed, balanced, nonlegislative approach in the previous governor’s administration. Specifically, the training course (a) makes an unfounded claim that there is a national reading crisis that can be traced to insufficient or inappropriate phonics instruction; (b) distorts, misrepresents, or omits relevant research findings and recommendations, most prominently from the report of the National Reading Panel; (c) inaccurately suggests that “balanced literacy instruction” is “whole language” instruction in disguise; and (d) wrongly claims that its views of phonics are based on a settled science of reading.
Merkel cell carcinoma (MCC) is an uncommon, but highly malignant, cutaneous tumor. Merkel cell polyoma virus (MCV) has been implicated in a majority of MCC tumors; however, viral-negative tumors have ...been reported to be more prevalent in some geographic regions subject to high sun exposure. While the impact of MCV and viral T-antigens on MCC development has been extensively investigated, little is known about the etiology of viral-negative tumors. We performed targeted capture and massively parallel DNA sequencing of 619 cancer genes to compare the gene mutations and copy number alterations in MCV-positive (n = 13) and -negative (n = 21) MCC tumors and cell lines. We found that MCV-positive tumors displayed very low mutation rates, but MCV-negative tumors exhibited a high mutation burden associated with a UV-induced DNA damage signature. All viral-negative tumors harbored mutations in RB1, TP53, and a high frequency of mutations in NOTCH1 and FAT1. Additional mutated or amplified cancer genes of potential clinical importance included PI3K (PIK3CA, AKT1, PIK3CG) and MAPK (HRAS, NF1) pathway members and the receptor tyrosine kinase FGFR2. Furthermore, looking ahead to potential therapeutic strategies encompassing immune checkpoint inhibitors such as anti-PD-L1, we also assessed the status of T-cell-infiltrating lymphocytes (TIL) and PD-L1 in MCC tumors. A subset of viral-negative tumors exhibited high TILs and PD-L1 expression, corresponding with the higher mutation load within these cancers. Taken together, this study provides new insights into the underlying biology of viral-negative MCC and paves the road for further investigation into new treatment opportunities.
Over the last few years, the development and relevance of
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F magnetic resonance imaging (MRI) for use in clinical practice has emerged. MRI using fluorinated probes enables the achievement of a ...specific signal with high contrast in MRI images. However, to ensure sufficient sensitivity of
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F MRI, fluorine probes with a high content of chemically equivalent fluorine atoms are required. The majority of
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F MRI agents are perfluorocarbon emulsions, which have a broad range of applications in molecular imaging, although the content of fluorine atoms in these molecules is limited. In this review, we focus mainly on polymer probes that allow higher fluorine content and represent versatile platforms with properties tailorable to a plethora of biomedical in vivo applications. We discuss the chemical development, up to the first imaging applications, of these promising fluorine probes, including injectable polymers that form depots that are intended for possible use in cancer therapy.
A challenge in tumor targeting is to deliver payloads to cancers while sparing normal tissues. A limited number of antibodies appear to meet this challenge as therapeutics themselves or as ...drug-antibody conjugates. However, antibodies suffer from their large size, which can lead to unfavorable pharmacokinetics for some therapeutic payloads, and that they are targeted against only a single epitope, which can reduce their selectivity and specificity. Here, we propose an alternative targeting approach based on patterns of cell surface proteins to rationally develop small, synthetic heteromultivalent ligands (htMVLs) that target multiple receptors simultaneously. To gain insight into the multivalent ligand strategy in vivo, we have generated synthetic htMVLs that contain melanocortin (MSH) and cholecystokinin (CCK) pharmacophores that are connected via a fluorescent labeled, rationally designed synthetic linker. These ligands were tested in an experimental animal model containing tumors that expressed only one (control) or both (target) MSH and CCK receptors. After systemic injection of the htMVL in tumor-bearing mice, label was highly retained in tumors that expressed both, compared with one, target receptors. Selectivity was quantified by using ex vivo measurement of Europium-labeled htMVL, which had up to 12-fold higher specificity for dual compared with single receptor expressing cells. This proof-of-principle study provides in vivo evidence that small, rationally designed bivalent htMVLs can be used to selectively target cells that express both, compared with single complimentary cell surface targets. These data open the possibility that specific combinations of targets on tumors can be identified and selectively targeted using htMVLs.
This work presents a design and experimental validation of a compact ultrawideband (UWB) bowtie antenna and balanced-to-unbalanced (balun) circuit for medical microwave imaging (MWI) applications ...working in the frequency band of 1-6 GHz. The UWB balun is perpendicularly attached to the planar bowtie arms, whose dimensions were miniaturized by rounding the bowtie edges. The antenna reflection coefficient was lower than −12 dB for tissues with a higher water content. The antenna possesses a high radiation efficiency (over 80%) and very low backward radiation. The predicted and measured specific absorption rate (SAR) distributions together with the electric field <inline-formula> <tex-math notation="LaTeX">\vert E\vert </tex-math></inline-formula> distribution proved a symmetrical radiation pattern. The potential of the presented antenna element was demonstrated by successful reconstruction of the images from the measured data by MWI methods. For this purpose, an MWI system equipped with eight antennas was implemented. The radar approach was used to determine the region of interest (ROI) where the area for microwave tomography reconstruction was identified. The dielectric properties within the ROI were reconstructed by using the Born approximation method at 1 GHz. This confirmed that the antenna can be used as the basis for more accurate multifrequency MWI systems and can be implemented in UWB MWI hybrid systems.
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A new series of enkephalin-like tetrapeptide analogs modified at the C-terminus by an N-(3,4-dichlorophenyl)-N-(piperidin-4-yl)propionamide (DPP) moiety were designed, synthesized, ...and tested for their binding affinities at opioid receptors and monoamine transporters to evaluate their potential multifunctional activity for the treatment of chronic pain. Most ligands exhibited high binding affinities in the nanomolar range at the opioid receptors with a slight delta-opioid receptor (DOR) selectivity over mu-opioid receptor (MOR) and kappa-opioid receptor (KOR) and low binding affinities in the micromolar range at the monoamine transporters, SERT and NET. Ligands of which the positions 1 and 4 were substituted by Dmt and Phe(4-X) residues, respectively, showed the excellent binding affinities at three opioid receptors. Among them, Dmt-d-Tic-Gly-Phe(4-F)-DPP was the most promising considering its excellent opioid affinities, particularly unexpected high binding affinity (Ki = 0.13 nM) at the KOR, and moderate interactions with serotonin/norepinephrine reuptake inhibitors (SNRIs). Docking studies revealed that the ligand was a good fit for the KOR binding pocket (binding score = 8,750).
The management of patients with biochemical, local, nodal, or oligometastatic relapsed prostate cancer has become more challenging and controversial. Novel imaging modalities designed to detect ...recurrence are increasingly used, particularly PSMA-PET scans in Australia, New Zealand and some European countries. Imaging techniques such as MRI and PET scans using other prostate cancer-specific tracers are also being utilised across the world. The optimal timing for commencing salvage treatment, and the role of local and/or systemic therapies remains controversial. Through surveys of the membership, the Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group (FROGG) identified wide variation in the management of recurrent prostate cancer. Following a workshop conducted in April 2017, the FROGG management committee reviewed the literature and developed a set of recommendations based on available evidence and expert opinion, for the appropriate investigation and management of recurrent prostate cancer. These recommendations cover the role and timing of post-prostatectomy radiotherapy, the management of regional nodal metastases and oligometastases, as well as the management of local prostate recurrence after definitive radiotherapy.
AbstractThe management of node-positive prostate cancer is highly variable, with both locoregional and systemic treatment options available. With the increasing use of novel imaging techniques such ...as PSMA-PET and MRI, combined with the increasing use of surgery for high-risk prostate cancer, clinical and pathological regional nodal disease is being detected at a higher rate and at an earlier stage than previously. This creates a window for a potentially curative management approach. The role of radiotherapy including optimal radiation target volumes and dose, as well as the timing and duration of accompanying systemic therapy remains uncertain. At a workshop in 2017, the Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group (FROGG) identified variations in the management of node-positive prostate cancer identified on primary staging or on histopathology at radical prostatectomy. FROGG reviewed the literature and developed a set of evidence-based recommendations on the appropriate investigation and management of clinically and pathologically node-positive prostate cancer. These recommendations encompass imaging techniques, radiation treatment target volumes and doses, as well as the use of androgen deprivation therapy.
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