87 research outputs found

    Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state

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    Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV

    Transthoracic three-dimensional echocardiography in adult patients with congenital heart disease

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    Objectives: This study sought to assess both the feasibility and potential role of transthoracic three-dimensional echocardiography for the evaluation of adult patients with congenital heart disease. Background: The unrestricted views with depth perception provided by three-dimensional echocardiography with dynamic volume-rendered display may enhance visualization of cardiac structures and detection of abnormalities in patients with congenital heart defects. Methods: We studied 33 patients with various heart defects (mitral valve anomalies in 9, aortic valve anomalies in 5, subaortic membrane in 5, ventricular septal defect in 4, transposition of the great arteries in 3, tetralogy of Fallot in 2, other defects in 5). Cross-sectional images of the specific region of interest were acquired from either the parasternal or apical window with the rotational technique (2° interval with electrocardiographic and respiratory gating) and postprocessed for resampling in cubic format. From these three-dimensional data sets a multitude of cut planes were selected, presented in volume-rendered dynamic display and analyzed by two observers for comparison with standard two-dimensional images to assess their additional information. Results: Three-dimensional reconstruction was possible in all patients. Structures of interest were evaluated from unusual viewpoints, providing both cardiologists and surgeons with immediate feedback. When compared with standard two-dimensional images, additional information was provided for 12 patients (36%). The mitral valve, aortoseptal continuity and interatrial septum were the structures for which three-dimensional echocardiography was most useful. Conclusions: Transthoracic three-dimensional echocardiography is feasible and facilitates spatial recognition of the intracardiac anatomy in a significant proportion of patients and enhances diagnostic confidence of complex congenital heart disease

    Direct mass measurements of 19B, 22C, 29F, 31Ne, 34Na and other light exotic nuclei

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    We report on direct time-of-flight based mass measurements of 16 light neutron-rich nuclei. These include the first determination of the masses of the Borromean drip-line nuclei 19^{19}B, 22^{22}C and 29^{29}F as well as that of 34^{34}Na. In addition, the most precise determinations to date for 23^{23}N and 31^{31}Ne are reported. Coupled with recent interaction cross-section measurements, the present results support the occurrence of a two-neutron halo in 22^{22}C, with a dominant ν2s1/22\nu2s_{1/2}^2 configuration, and a single-neutron halo in 31^{31}Ne with the valence neutron occupying predominantly the 2p3/2p_{3/2} orbital. Despite a very low two-neutron separation energy the development of a halo in 19^{19}B is hindered by the 1d5/22d_{5/2}^2 character of the valence neutrons.Comment: 5 page

    A retrospective description of primary immuno­deficiency diseases at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa, 1975 - 2017

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    Background. The primary immunodeficiency diseases (PIDs) constitute a diverse and ever-expanding group of inborn errors affecting a wide range of immune functions. They are not well documented in sub-Saharan Africa.Objectives. To describe the spectrum of PIDs at a tertiary paediatric hospital.Methods. A retrospective descriptive study of PIDs diagnosed at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa (SA), between 1975 and 2017 was undertaken.Results. We identified 252 children with PIDs, spanning eight of the nine categories listed in the 2017 classification of the International Union of Immunological Societies. Predominantly antibody deficiencies, combined immunodeficiencies with associated syndromic features, and immunodeficiencies affecting cellular and humoral immunity accounted for most children with PIDs (n=199, 79.0%). The mean age (standard deviation) at diagnosis was 46 (50) months, and the male/female ratio was 1.5:1. There was a history of parental consanguinity in 3 cases (1.2%). Recurrent infection was the most prevalent presenting phenotype, manifesting in 177 patients (70.2%). Genetic or chromosomal confirmation was obtained in 42/252 cases (16.7%). Common interventions used to prevent infection were antimicrobial prophylaxis and immunoglobulin replacement therapy, administered to 95 (37.7%) and 93 (36.9%) of the patients, respectively. Six of 7 children who underwent haematopoietic stem cell transplantation (HSCT) had successful outcomes. The 7th patient died 2 months after HSCT from overwhelming infection. Although we could not account for the children lost to follow-up during the study period, 53 deaths were confirmed (21.0%).Conclusions. Several challenges exist in the recognition and treatment of children with PIDs in our setting. These include limited access to genetic diagnostics and HSCT. Suboptimal treatment options contribute to the overall mortality of PIDs in SA.

    Performance of the improved larger acceptance spectrometer: VAMOS++

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    International audienceMeasurements and ion optic calculations showed that the large momentum acceptance of the VAMOS spectrometer at GANIL could be further increased from \sim 11% to \sim 30% by suitably enlarging the dimensions of the detectors used at the focal plane. Such a new detection system built for the focal plane of VAMOS is described. It consists of larger area detectors (1000 mm × 150 mm) namely, a Multi-Wire Parallel Plate Avalanche Counter (MWPPAC), two drift chambers, a segmented ionization chamber and an array of Si detectors. Compared to the earlier existing system (VAMOS), we show that the new system (VAMOS++) has a dispersion-independent momentum acceptance . Additionally a start detector (MWPPAC) has been introduced near the target to further improve the mass resolution to \sim 1/220. The performance of the VAMOS++ spectrometer is demonstrated using measurements of residues formed in the collisions of 129Xe at 967 MeV on 197Au

    MAYA: An active-target detector for binary reactions with exotic beams

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    International audienceWith recent improvements in the production of radioactive beams in facilities such as SPIRAL at GANIL, a larger area of the nuclear chart is now accessible for experimentation. For these usually low-intensity and low-energy secondary beams, we have developed the new MAYA detector based on the active-target concept. This device allows to use a relatively thick target without loss of resolution by using the detection gas as target material. Dedicated 3D tracking, particle identification, energy loss and range measurements allow complete kinematic reconstruction of reactions taking place inside MAYA

    Mass Measurements near N=Z

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    Abstract After an outline of the physics motivations, that illustrate why we think it is important to measure masses in the region N≈Z, we report on on experiments performed at Ganil. An experiment aimed at measuring the masses of proton-rich nuclei in the mass region A ≈ 60–80 has been performed, using a direct time-of-flight technique in conjunction with SISSI and the SPEG spectrometer at GANIL. The nuclei were produced via the fragmentation of a 78 Kr beam (73 meV/nucleon). A novel technique for the purification of the secondary beams, based on the stripping of the ions and using the α and the SPEG spectrometers, was succesfully checked. It allows for good selectivity without altering the beam quality. Secondary ions of 100 Ag, 100 Cd, 100 In and 100 Sn were produced via the fusion-evaporation reaction 50 Cr + 58 Ni at an energy of 5.1 MeV/nucleon, and were accelerated simultaneously in the second cyclotron of GANIL (CSS2). About 10 counts were observed from the production and acceleration of 100 Sn 22+ . The masses of 100 Cd, 100 In and 100 Sn were measured with respect to 100 Ag using the CSS2 cyclotron, with precisions of 2 × 10 −6 , 3 × 10 −6 and 10 −5 respectively

    Reuse of oak chips for modification of the volatile fraction of alcoholic beverages

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    New or used barrels can be applied in ageing of alcoholic beverages. Compounds adsorbed in wood migrate between beverages along with wood extractives. As barrel ageing is costly and time-consuming, processes using wood fragments have been gaining interest. These generate wood residues for which the reuse is still not well established. This work aims at the reuse of oak fragments for the additive ageing of alcoholic beverages. Oak chips, previously immersed in fortified wine, were applied to beer, wine and grape marc spirit. Wood compounds and adsorbed wine volatiles were extracted, with more impact and satisfactory yields on beer composition. Also, wood adsorbed beverages compounds in a subtractive ageing phenomena. Beer formulations using different binomial wood concentration/temperature combinations were generated and presented to trained tasters. Higher temperatures and wood concentrations led to prominence of wood descriptors and lower perception of fruity and floral aromas, reflecting the changes in chemical composition.Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 – Programa Operacional Regional do Norte. Fermentum – Engenharia das Fermentações Lda. also participated in co-funding and provided beer samples used in this work, which authors would like to acknowledge. Lastly, authors would like to thank Mr. Benoît Verdier and Seguin Moreau for supplying the woods and Mr. Paulo Coutinho and Quinta do Portal for supplying the fortified wineinfo:eu-repo/semantics/publishedVersio

    Chromosome Observation of Stephania cepharantha HAYATA

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    1.玉咲ツヅラフヂ(Stephania cepharantha HAYATA)の栽培に於いて, 雄株と雌株の比は栽培観察者の云う如く雌本が少いと云う事は無く, 大体1 : 1に分離す。2.雄株の減数分裂に於いてn=13なる事がたしかめられ形態的に見てXYなる性染色体の存在する事を認めた。3.雌雄両株の体細胞に於いて2n=26なる染色体が算えられた。雄株は24の常染色体とXYなる性染色体を持ち, 雌株は24の常染色体とXXなる性染色体を持つ事が認められた。 / The separating ratio of female and male plants of Stephania cepharantha HAYATA was almost equally expressed. The somatic chromosome numbers of them were both 26. The female plant had 24 autosom and XX chromosomes; in the other hand, the male had 24 autosom and XY chromosomes. At meiosis in P. M. Cs., the number of reduced chromosomes was found to be 13 at polar views in the heterotypic metaphase. One unequal pair of chromosomes was observed in polar and side views of the heterotypic metephase. One of its two members was about 1.5-2.0 larger than the other
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