There are many challenges in building an ultra-wideband (UWB) indoor local positioning system for high-accuracy applications. These challenges include reduced accuracy due to multipath interference, ...sampling rate limitations, tag synchronization, and antenna phase-center variation. Each of these factors must be addressed to achieve millimeter or sub-millimeter accuracy. The developed system architecture is presented where a 300-ps Gaussian pulse modulates an 8-GHz carrier signal and is transmitted through an omni-directional UWB antenna. Receiver-side peak detection, a low-cost subsequential-sampling mixer utilizing a direct digital synthesizer, high fidelity 10-MHz crystals, and Vivaldi phase-center calibration are utilized to mitigate these challenging problems. Synchronized and unsynchronized experimental results validated with a sub-millimeter accurate optical tracking system are presented with a detailed discussion of various system errors.
ABSTRACT
The Palomar Fiber Nuller (PFN) is a rotating-baseline nulling interferometer that enables high-accuracy near-infrared (NIR) nulling observations with full azimuth coverage. To achieve NIR ...null-depth accuracies of several x 10−4, the PFN uses a common-mode optical system to provide a high degree of symmetry, single-mode-fibre beam combination to reduce sensitivity to pointing and wavefront errors, extreme adaptive optics to stabilize the fibre coupling and the cross-aperture fringe phase, rapid signal calibration and camera readout to minimize temporal effects, and a statistical null-depth fluctuation analysis to relax the phase stabilization requirement. Here, we describe the PFN’s final design and performance and provide a demonstration of faint-companion detection by means of nulling-baseline rotation, as originally envisioned for space-based nulling interferometry. Specifically, the Ks-band null-depth rotation curve measured on the spectroscopic binary η Peg reflects both a secondary star 1.08 ± 0.06 × 10−2 as bright as the primary, and a null-depth contribution of 4.8 ± 1.6 × 10−4 due to the size of the primary star. With a 30 mas separation at the time, η Peg B was well inside both the telescope’s diffraction-limited beam diameter (88 mas) and typical coronagraphic inner working angles. Finally, we discuss potential improvements that can enable a number of small-angle nulling observations on larger telescopes.
The recent Zika virus (ZIKV) epidemic has been linked to unusual and severe clinical manifestations including microcephaly in fetuses of infected pregnant women and Guillian-Barré syndrome in adults. ...Neutralizing antibodies present a possible therapeutic approach to prevent and control ZIKV infection. Here we present a 6.2 Å resolution three-dimensional cryo-electron microscopy (cryoEM) structure of an infectious ZIKV (strain H/PF/2013, French Polynesia) in complex with the Fab fragment of a highly therapeutic and neutralizing human monoclonal antibody, ZIKV-117. The antibody had been shown to prevent fetal infection and demise in mice. The structure shows that ZIKV-117 Fabs cross-link the monomers within the surface E glycoprotein dimers as well as between neighbouring dimers, thus preventing the reorganization of E protein monomers into fusogenic trimers in the acidic environment of endosomes.
The emergence of Zika virus (ZIKV) as a major public health threat has focused research on understanding virus biology and developing a suite of strategies for disease intervention. Recent advances ...in cryoelectron microscopy have accelerated structure-function studies of flaviviruses and of ZIKV in particular. Structures of the mature and immature ZIKV have demonstrated its similarity with other known flaviviruses such as dengue and West Nile viruses. However, ZIKV’s unique pathobiology demands an explanation of how its structure, although similar to its flavivirus relatives, is sufficiently unique to address questions of receptor specificity, transmission, and antigenicity. Progress in defining the immunodominant epitopes and how neutralizing antibodies bind to them will provide great insight as vaccines progress through clinical trials. Identification of host receptors will substantially illuminate the interesting ZIKV tropism and provide insights into pathogenesis. Although the answers to all of these questions are not yet available, rapid progress in combining structural biology with other techniques is revealing the similarities and the differences in virion structure and function between ZIKV and related flaviviruses.
But : Le but de cette étude est d’évaluer le niveau de stress oxydatif à l’aide d’un marqueur biologique sensible et spécifique, le 8-isoprostane (8-IP), chez des patients admis en service ...d’endocrinologie pour décompensation de diabète de type 2. Patients et méthodes : Vingt-six patients (9F, 56 ± 10 ans ; 17H, 64 ± 9 ans)(m ± SD) ont été étudiés le jour de l’hospitalisation et à la sortie, 6 ± 2 jours après admission, avec mesure des concentrations urinaires en 8-IP, des glycémies à jeun (Gly), de l’HbA1c et de l’IMC. L’analyse automatisée du 8-IP est réalisée par immunoenzymologie en plaques 96 puits en dupliqué (EtiMax 3000, DiaSorin ; réactifs Cayman), après purification des urines sur colonnes d’affinité (Cayman), les résultats sont exprimés en ng/mmol de créatinine. Les tests statistiques non-paramétriques de Wilcoxon (variations entrée Vs sortie des 8-IP, Gly et IMC) et de Spearman (corrélations 8-IP/Gly) ont été utilisés. Résultats : A l’admission, on note une HbA1c à 10,2 ± 1,6 % une hyperglycémie à jeun (1,93 ± 0,66 g/L) et une hyper-excrétion urinaire de 8-IP (121 ± 82 ng/mmol ; N : < 80), et un IMC de 33,9 ± 6,5 kg/m2 ;. A la sortie (durée d’hospitalisation : 4–10 j), on observe une diminution de l’excrétion de 8-IP (105 ± 69 ng/mmol, p = 0,045), accompagnée par celles de la Gly (1,44 ± 0,33 g/L, p = 0,0025) et de l’IMC (–0,9 kg/m2 ;, p = 0,0033). L’évolution des Gly et des IMC était la même que celle des 8-IP, respectivement chez 62 % et 67 % patients, sans corrélation entre la baisse du stress oxydatif et la Gly. Conclusion : La situation de décompensation du diabète de type 2 est accompagnée par un stress oxydatif qui diminue après une hospitalisation de courte durée, sans corrélation significative toutefois avec l’amélioration de la glycémie à jeun. Le niveau encore élevé de 8-IP à la sortie suggère que d’autres approches thérapeutiques telles qu’une complémentation nutritionnelle en antioxydants pourrait être évaluée chez ces patients.
Context:
Multiple endocrine neoplasia Type-1 (MEN1) in young patients is only described by case reports.
Objective:
To improve the knowledge of MEN1 natural history before 21 years old.
Methods:
...Obtain a description of the first symptoms occurring before 21 years old (clinical symptoms, biological or imaging abnormalities), surgical outcomes related to MEN1 Neuro Endocrine Tumors (NETs) occurring in a group of 160 patients extracted from the “Groupe d'étude des Tumeurs Endocrines” MEN1 cohort.
Results:
The first symptoms were related to hyperparathyroidism in 122 cases (75%), pituitary adenoma in 55 cases (34%), nonsecreting pancreatic tumor (NSPT) in 14 cases (9%), insulinoma in 20 cases (12%), gastrinoma in three cases (2%), malignant adrenal tumors in 2 cases (1%), and malignant thymic-NET in one case (1%). Hyperparathyrodism was the first lesion in 90 cases (56%). The first symptoms occurred before 10 years old in 22 cases (14%) and before 5 years old in five cases (3%). Surgery was performed before age 21 in 66 patients (41%) with a total of 74 operations: pituitary adenoma (n = 9, 16%), hyperparathyroidism (n = 38, 31%), gastrinoma (n = 1, 33%), NSPT (n = 5, 36%), and all cases of insulinoma, adrenal tumors, and thymic-NET. One patient died before age 21 due to a thymic-NET. Overall, lesions were malignant in four cases.
Conclusions:
Various MEN1 lesions occurred frequently before 21 years old, but mainly after 10 years of age. Rare, aggressive tumors may develop at any age. Hyperparathyroidism was the most frequently encountered lesion but was not always the first biological or clinical abnormality to appear during the course of MEN1.
Process Technology Variation Kuhn, K. J.; Giles, M. D.; Becher, D. ...
IEEE transactions on electron devices,
2011-Aug., 2011-08-00, 20110801, Letnik:
58, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Moore's law technology scaling has improved performance by five orders of magnitude in the last four decades. As advanced technologies continue the pursuit of Moore's law, a variety of challenges ...will need to be overcome. One of these challenges is the management of process variation. This paper discusses the importance of process variation in modern transistor technology, reviews front-end variation sources, presents device and circuit variation measurement techniques, including circuit and memory data from the 32-nm node, and compares recent intrinsic transistor variation performance from the literature.
The outbreak of Zika virus (ZIKV) in 2016 created worldwide health emergency which demand urgent research efforts on understanding the virus biology and developing therapeutic strategies. Here, we ...present a time-resolved chemical proteomic strategy to track the early-stage entry of ZIKV into host cells. ZIKV was labeled on its surface with a chemical probe, which carries a photocrosslinker to covalently link virus-interacting proteins in living cells on UV exposure at different time points, and a biotin tag for subsequent enrichment and mass spectrometric identification of the receptor or other host proteins critical for virus internalization. We identified Neural Cell Adhesion Molecule (NCAM1) as a potential ZIKV receptor and further validated it through overexpression, knockout, and inhibition of NCAM1 in Vero cells and human glioblastoma cells U-251 MG. Collectively, the strategy can serve as a universal tool to map virus entry pathways and uncover key interacting proteins.
Sindbis virus (SINV genus
, family
) is an enveloped, mosquito-borne virus. Alphaviruses cause cytolytic infections in mammalian cells while establishing noncytopathic, persistent infections in ...mosquito cells. Mosquito vector adaptation of alphaviruses is a major factor in the transmission of epidemic strains of alphaviruses. Though extensive studies have been performed on infected mammalian cells, the morphological and structural elements of alphavirus replication and assembly remain poorly understood in mosquito cells. Here we used high-resolution live-cell imaging coupled with single-particle tracking and electron microscopy analyses to delineate steps in the alphavirus life cycle in both the mammalian host cell and insect vector cells. Use of dually labeled SINV in conjunction with cellular stains enabled us to simultaneously determine the spatial and temporal differences of alphavirus replication complexes (RCs) in mammalian and insect cells. We found that the nonstructural viral proteins and viral RNA in RCs exhibit distinct spatial organization in mosquito cytopathic vacuoles compared to replication organelles from mammalian cells. We show that SINV exploits filopodial extensions for virus dissemination in both cell types. Additionally, we propose a novel mechanism for replication complex formation around glycoprotein-containing vesicles in mosquito cells that produced internally released particles that were seen budding from the vesicles by live imaging. Finally, by characterizing mosquito cell lines that were persistently infected with fluorescent virus, we show that the replication and assembly machinery are highly modified, and this allows continuous production of alphaviruses at reduced levels.
Reemerging mosquito-borne alphaviruses cause serious human epidemics worldwide. Several structural and imaging studies have helped to define the life cycle of alphaviruses in mammalian cells, but the mode of virus replication and assembly in the invertebrate vector and mechanisms producing two disease outcomes in two types of cells are yet to be identified. Using transmission electron microscopy and live-cell imaging with dual fluorescent protein-tagged SINV, we show that while insect and mammalian cells display similarities in entry and exit, they present distinct spatial and temporal organizations in virus replication and assembly. By characterizing acutely and persistently infected cells, we provide new insights into alphavirus replication and assembly in two distinct hosts, resulting in high-titer virus production in mammalian cells and continuous virus production at reduced levels in mosquito cells-presumably a prerequisite for alphavirus maintenance in nature.
Many viruses go through a maturation step in the final stages of assembly before being transmitted to another host. The maturation process of flaviviruses is directed by the proteolytic cleavage of ...the precursor membrane protein (prM), turning inert virus into infectious particles. We have determined the 2.2 angstrom resolution crystal structure of a recombinant protein in which the dengue virus prM is linked to the envelope glycoprotein E. The structure represents the prM-E heterodimer and fits well into the cryo-electron microscopy density of immature virus at neutral pH. The pr peptide β-barrel structure covers the fusion loop in E, preventing fusion with host cell membranes. The structure provides a basis for identifying the stages of its pH-directed conformational metamorphosis during maturation, ending with release of pr when budding from the host.
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