376 research outputs found
Intravascular Polarimetry: Clinical Translation and Future Applications of Catheter-Based Polarization Sensitive Optical Frequency Domain Imaging
Optical coherence tomography (OCT) and optical frequency domain imaging (OFDI)
visualize the coronary artery wall and plaque morphology in great detail. The advent of
these high-resolution intracoronary imaging modalities has propelled our understanding
of coronary atherosclerosis and provided enhanced guidance for percutaneous coronary
intervention. Yet, the lack of contrast between distinct tissue types and plaque
compositions impedes further elucidation of the complex mechanisms that contribute
to acute coronary syndrome (ACS) and hinders the prospective identification of
plaques susceptible to rupture. Intravascular polarimetry with polarization-sensitive
OFDI measures polarization properties of the coronary arterial wall using conventional
intravascular imaging catheters. The quantitative polarization metrics display notable
image contrast between several relevant coronary plaque microstructures that are difficult
to identify with conventional OCT and OFDI. Tissues rich in collagen and smooth
muscle cells exhibit birefringence, while lipid and macrophages cause depolarization.
In this review, we describe the basic principles of intravascular polarimetry, discuss the
interpretation of the polarization signatures, and outline promising avenues for future
research and clinical implications
Effect of oral calcium loading on intact PTH and calcitriol in idiopathic renal calcium stone formers and healthy controls
The calciuric response after an oral calcium load (l000 mg elemental calcium together with a standard breakfast) was studied in 13 healthy male controls and 21 recurrent idiopathic renal calcium stone formers, 12 with hypercalciuria (UCa×V>7.50 mmol/24 h) and nine with normocalciuria. In controls, serum 1,25(OH)2 vitamin D3 (calcitriol) remained unchanged 6 h after oral calcium load (50.6±5.1 versus 50.9±5.0 pg/ml), whereas it tended to increase in hypercalciuric (from 53.6±3.2 to 60.6±5.4 pg/ml, P=0.182) and fell in normocalciuric stone formers (from 45.9±2.6 to 38.1±3.3 pg/ml, P=0.011). The total amount of urinary calcium excreted after OCL was 2.50±0.20 mmol in controls, 2.27±0.27 mmol in normocalciuric and 3.62±0.32 mmol in hypercalciuric stone formers (P=0.005 versus controls and normocalciuric stone formers respectively); it positively correlated with serum calcitriol 6 h after calcium load (r=0.392, P=0.024). Maximum increase in urinary calcium excretion rate, δCa-Emax, was inversely related to intact PTH levels in the first 4 h after calcium load, i.e. more pronounced PTH suppression predicted a steeper increase in urinary calcium excretion rate. Twenty-four-hour urine calcium excretion rate was inversely related to the ratio of δ calcitriol/δPTHmax after calcium load (r=−0.653, P=0.0001), indicating that an abnormally up-regulated synthesis of calcitriol and consecutive relative PTH suppression induce hypercalciuria. Finally, late absorption of calcium as suggested by maximum urinary calcium excretion beyond 4 h after oral calcium load was as rare in hypercalciuric stone formers (2 of 12) as in controls (1 of 13) and did not occur in normocalciuric stone former
Analysis of site-specific N-glycan remodeling in the endoplasmic reticulum and the Golgi
The hallmark of N-linked protein glycosylation is the generation of diverse glycan structures in the secretory pathway. Dynamic, non-template-driven processes of N-glycan remodeling in the endoplasmic reticulum and the Golgi provide the cellular setting for structural diversity. We applied newly developed mass spectrometry-based analytics to quantify site-specific N-glycan remodeling of the model protein Pdi1p expressed in insect cells. Molecular dynamics simulation, mutational analysis, kinetic studies of in vitro processing events and glycan flux analysis supported the defining role of the protein in N-glycan processin
Virtual reality rehabilitation system for neuropathic pain and motor dysfunction in spinal cord injury patients
Spinal cord injury (SCI) causes both lower limb motor dysfunction and associated neuropathic pain. Although these two conditions share related cortical mechanisms, different interventions are currently used to treat each condition. With intensive training using entertaining virtual reality (VR) scenarios, it may be possible to reshape cortical networks thereby reducing neuropathic pain and improving motor function. We have created the first VR training system combining action observation and execution addressing lower limb function in incomplete SCI (iSCI) patients. A particular feature of the system is the use of size-adjustable shoes with integrated motion sensors. A pilot single-case clinical study is currently being conducted on six iSCI patients. Two patients tested to date were highly motivated to perform and reported improved physical well-being. They improved in playing skill and in controlling the virtual lower limbs. There were post-intervention indications of neuropathic pain decrease, muscle strength increase, faster walking speed and improved performance on items relevant for ambulation. In addition functional MRI before and after treatment revealed a decreased activation pattern. We interpret this result as an improvement of neuronal synergies for this task. These results suggest that our VR system may be beneficial for both reducing neuropathic pain and improving motor function in iSCI patients
Development of SRF Cavity Tuners for CERN
Superconducting RF cavity developments are currently on-going for new accelerator projects at CERN such as HIE ISOLDE and HL-LHC. Mechanical RF tuning systems are required to compensate cavity frequency shifts of the cavities due to temperature, mechanical, pressure and RF effects on the cavity geometry. A rich history and experience is available for such mechanical tuners developed for existing RF cavities. Design constraints in the context of HIE ISOLDE and HL-LHC such as required resolution, space limitation, reliability and maintainability have led to new concepts in the tuning mechanisms. This paper will discuss such new approaches, their performances and planned developments
The CERN PS multi-turn extraction based on beam splittting in stable islands of transverse phase space: Design Report
Since 2001 considerable effort has been devoted to the study of a possible replacement of the continuous-transfer extraction mode from the PS to the SPS. Such an approach, called Multi-Turn Extraction (MTE), is based on capture of the beam inside stable islands of transverse phase space, generated by sextupoles and octupoles, thanks to a properly chosen tune variation. Both numerical simulations and measurements with beam were performed to understand the properties of this new extraction mode. The experimental study was completed at the end of 2004 and by the end of 2005 a scheme to implement this novel approach in the PS machine was defined and its performance assessed. This design report presents the outcome of the studies undertaken both in terms of technical issues as well as of resources necessary to implement the proposed scheme
Isotopic measurements in water vapor, precipitation, and seawater during EURECA
n early 2020, an international team set out to investigate trade-wind cumulus clouds and their coupling to the large-scale circulation through the field campaign EURECA: ElUcidating the RolE of Clouds-Circulation Coupling in ClimAte. Focused on the western tropical Atlantic near Barbados, EURECA deployed a number of innovative observational strategies, including a large network of water isotopic measurements collectively known as EURECA-iso, to study the tropical shallow convective environment. The goal of the isotopic measurements was to elucidate processes that regulate the hydroclimate state – for example, by identifying moisture sources, quantifying mixing between atmospheric layers, characterizing the microphysics that influence the formation and persistence of clouds and precipitation, and providing an extra constraint in the evaluation of numerical simulations. During the field experiment, researchers deployed seven water vapor isotopic analyzers on two aircraft, on three ships, and at the Barbados Cloud Observatory (BCO). Precipitation was collected for isotopic analysis at the BCO and from aboard four ships. In addition, three ships collected seawater for isotopic analysis. All told, the in situ data span the period 5 January–22 February 2020 and cover the approximate area 6 to 16° N and 50 to 60° W, with water vapor isotope ratios measured from a few meters above sea level to the mid-free troposphere and seawater samples spanning the ocean surface to several kilometers depth.
This paper describes the full EURECA isotopic in situ data collection – providing extensive information about sampling strategies and data uncertainties – and also guides readers to complementary remotely sensed water vapor isotope ratios. All field data have been made publicly available even if they are affected by known biases, as is the case for high-altitude aircraft measurements, one of the two BCO ground-based water vapor time series, and select rain and seawater samples from the ships. Publication of these data reflects a desire to promote dialogue around improving water isotope measurement strategies for the future. The remaining, high-quality data create unprecedented opportunities to close water isotopic budgets and evaluate water fluxes and their influence on cloudiness in the trade-wind environment. The full list of dataset DOIs and notes on data quality flags are provided in Table 3 of Sect. 5 (“Data availability”)
Influence of bisphosphonate therapy on bone geometry, volumetric bone density and bone strength of femoral shaft in postmenopausal women with rheumatoid arthritis
Expression of a protein involved in bone resorption, Dkk1, is activated by HTLV-1 bZIP factor through its activation domain
<p>Abstract</p> <p>Background</p> <p>Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia, a malignancy characterized by uncontrolled proliferation of virally-infected CD4+ T-cells. Hypercalcemia and bone lesions due to osteoclast-mediated bone resorption are frequently associated with more aggressive forms of the disease. The HTLV-1 provirus contains a unique antisense gene that expresses HTLV-1 basic leucine zipper (bZIP) factor (HBZ). HBZ is localized to the nucleus where it regulates levels of transcription by binding to certain cellular transcriptional regulators. Among its protein targets, HBZ forms a stable complex with the homologous cellular coactivators, p300 and CBP, which is modulated through two N-terminal LXXLL motifs in the viral protein and the conserved KIX domain in the coactivators.</p> <p>Results</p> <p>To determine the effects of these interactions on transcription, we performed a preliminary microarray analysis, comparing levels of gene expression in cells with wild-type HBZ versus cells with HBZ mutated in its LXXLL motifs. <it>DKK1</it>, which encodes the secreted Wnt signaling inhibitor, Dickkopf-1 (Dkk1), was confirmed to be transcriptionally activated by HBZ, but not its mutant. Dkk1 plays a major role in the development of bone lesions caused by multiple myeloma. In parallel with the initial findings, activation of Dkk1 expression by HBZ was abrogated by siRNA-mediated knockdown of p300/CBP or by a truncated form of p300 containing the KIX domain. Among HTLV-1-infected T-cell lines tested, the detection of Dkk1 mRNA partially correlated with a threshold level of HBZ mRNA. In addition, an uninfected and an HTLV-1-infected T-cell line transfected with an HBZ expression vector exhibited <it>de novo </it>and increased DKK1 transcription, respectively. In contrast to HBZ, The HTLV-1 Tax protein repressed Dkk1 expression.</p> <p>Conclusions</p> <p>These data indicate that HBZ activates Dkk1 expression through its interaction with p300/CBP. However, this effect is limited in HTLV-1-infected T-cell lines, which in part, may be due to suppression of Dkk1 expression by Tax. Consequently, the ability of HBZ to regulate expression of Dkk1 and possibly other cellular genes may only be significant during late stages of ATL, when Tax expression is repressed.</p
The Influence of International Law on the International Movement of Persons
Many migration theories identify ‘the law’ as a significant constraint on the international
movement of persons. While this constraint often operates through national migration
legislation, this study examines the influence of international law in shaping contemporary
patterns in the international movement of persons at the macro level. The analysis begins with an
examination of the long-established power of a State to regulate cross-border movement of
persons as an inherent attribute of State sovereignty, together with the accepted limitations on a
State’s power to control entry and exit. Yet, international law reaches well beyond the movement
of people across borders. The development of international human rights law has been a key
constraint on state action in the United Nations era by also regulating the treatment of migrants
within a State’s borders. The study considers how international law has responded to current
migration issues, including: protection of migrant women and children; suppression of
smuggling and trafficking of people; labour migration; and environmental migration. As in other
areas of international society, there has been a proliferation of institutions through which
international migration law is made and enforced. The most prominent among them are the
United Nations High Commissioner for Refugees (UNHCR) and the International Organization
for Migration (IOM), but the establishment of other entities with overlapping mandates has given
rise to calls for a new international migration regime based on streamlined institutional
arrangements. The study concludes that international law is an imperfect framework for
regulating the international movement of persons because it has developed in a piecemeal
fashion over a long time to deal with issues of concern at particular points in human history. Yet,
despite its shortfalls, international law and its associated institutions unquestionably play a most
important role in constraining and channeling state authority over the international movement of
persons
- …