441 research outputs found
Elements of Biblical Exegesis: A Basic Guide for Students and Ministers [review] / Michael J. Gorman
Vaccination of rabbits with immunodominant antigens from Sarcoptes scabiei induced high levels of humoral responses and pro-inflammatory cytokines but confers limited protection
Vaccination is an attractive ecological alternative to the use of acaricides for parasite control. However, effective anti-parasite vaccines against sarcoptic mange have not yet been developed. The purpose of this study was first to identify Sarcoptes scabiei immunodominant antigens and second to evaluate them as vaccine candidates in a rabbit/ S. scabiei var. cuniculi model. The S. scabiei Ssλ15 immunodominant antigen was selected by immunoscreening of a S. scabiei var. hominis cDNA. The full-length cDNA was sequenced and cloned into the pGEX vector and the recombinant protein expressed in BL21 (DE3) cells and purified. A vaccination trial was performed consisting of a test group (n = 8) immunised with recAgs (a mix of two recombinant antigens, Ssλ15 and the previously described Ssλ20∆B3) and a control group (n = 8) immunised with PBS. All analyses were performed with R Statistical Environment with α set at 0.050. The full-length open reading frame of the 1,821 nt cloned cDNA encodes a 64 kDa polypeptide, the sequence of which had 96 % identity with a hypothetical protein of S. scabiei. Ssλ15 was localised by immunostaining of skin sections in the tegument surrounding the mouthparts and the coxa in the legs of mites. Rabbit immunisation with recAgs induced high levels of specific IgG (P < 0.010) and increased levels of total IgEs. However, no significant clinical protection against S. scabiei challenge was detected. Unexpectedly, the group immunised with the recAgs mix had significantly higher lesion scores (P = 0.050) although lower mean mite densities than those observed in the control group. These results might indicate that the lesions in the recAgs group were due not only to the mites density but also to an exacerbated immunological response after challenge, which is in agreement with the specific high levels of pro-inflammatory cytokines (IL-1 and TNFα) detected after challenge in this group. The selected antigens delivered as recombinant proteins had no clinical protective efficacy against S. scabiei infestation although immunisation reduced mite density. However, these results pave the way for future studies on alternative production systems, adjuvants, delivery methods and combinations of antigens in order to manage stimulation of clinical protective immune responses. The online version of this article (doi:10.1186/s13071-016-1717-9) contains supplementary material, which is available to authorized users
Radiative transfer with scattering for domain-decomposed 3D MHD simulations of cool stellar atmospheres
We present the implementation of a radiative transfer solver with coherent
scattering in the new BIFROST code for radiative magneto-hydrodynamical (MHD)
simulations of stellar surface convection. The code is fully parallelized using
MPI domain decomposition, which allows for large grid sizes and improved
resolution of hydrodynamical structures. We apply the code to simulate the
surface granulation in a solar-type star, ignoring magnetic fields, and
investigate the importance of coherent scattering for the atmospheric
structure. A scattering term is added to the radiative transfer equation,
requiring an iterative computation of the radiation field. We use a
short-characteristics-based Gauss-Seidel acceleration scheme to compute
radiative flux divergences for the energy equation. The effects of coherent
scattering are tested by comparing the temperature stratification of three 3D
time-dependent hydrodynamical atmosphere models of a solar-type star: without
scattering, with continuum scattering only, and with both continuum and line
scattering. We show that continuum scattering does not have a significant
impact on the photospheric temperature structure for a star like the Sun.
Including scattering in line-blanketing, however, leads to a decrease of
temperatures by about 350\,K below log tau < -4. The effect is opposite to that
of 1D hydrostatic models in radiative equilibrium, where scattering reduces the
cooling effect of strong LTE lines in the higher layers of the photosphere.
Coherent line scattering also changes the temperature distribution in the high
atmosphere, where we observe stronger fluctuations compared to a treatment of
lines as true absorbers.Comment: A&A, in pres
Healthy ageing and home: The perspectives of very old people in five European countries
This paper reports on in-depth research, using a grounded theory approach, to examine the ways in which very old people perceive healthy ageing in the context of living alone at home within urban settings in five European countries. This qualitative study was part of a cross-national project entitled ENABLE-AGE which examined the relationship between home and healthy ageing. Interviews explored the notion of healthy ageing, the meaning and importance of home, conceptualisations of independence and autonomy and links between healthy ageing and home. Data analysis identified five ways in which older people constructed healthy ageing: home and keeping active; managing lifestyles, health and illness; balancing social life; and balancing material and financial circumstances. Older people reflected on their everyday lives at home in terms of being engaged in purposeful, meaningful action and evaluated healthy ageing in relation to the symbolic and practical affordances of the home, contextualised within constructions of their national context. The research suggests that older people perceive healthy ageing as an active achievement, created through individual, personal effort and supported through social ties despite the health, financial and social decline associated with growing older. The physicality and spatiality of home provided the context for establishing and evaluating the notion of healthy ageing, whilst the experienced relationship between home, life history and identity created a meaningful space within which healthy ageing was negotiated
Focal adhesion genes refine the intermediate-risk cytogenetic classification of acute myeloid leukemia
© 2018 by the authors.In recent years, several attempts have been made to identify novel prognostic markers in patients with intermediate-risk acute myeloid leukemia (IR-AML), to implement risk-adapted strategies. The non-receptor tyrosine kinases are proteins involved in regulation of cell growth, adhesion, migration and apoptosis. They associate with metastatic dissemination in solid tumors and poor prognosis. However, their role in haematological malignancies has been scarcely studied. We hypothesized that PTK2/FAK, PTK2B/PYK2, LYN or SRC could be new prognostic markers in IR-AML. We assessed PTK2, PTK2B, LYN and SRC gene expression in a cohort of 324 patients, adults up to the age of 70, classified in the IR-AML cytogenetic group. Univariate and multivariate analyses showed that PTK2B, LYN and PTK2 gene expression are independent prognostic factors in IR-AML patients. PTK2B and LYN identify a patient subgroup with good prognosis within the cohort with non-favorable FLT3/NPM1 combined mutations. In contrast, PTK2 identifies a patient subgroup with poor prognosis within the worst prognosis cohort who display non-favorable FLT3/NPM1 combined mutations and underexpression of PTK2B or LYN. The combined use of these markers can refine the highly heterogeneous intermediate-risk subgroup of AML patients, and allow the development of risk-adapted post-remission chemotherapy protocols to improve their response to treatment.Pallarès, VictorThis work was supported by Instituto de Salud Carlos III (Co-funding from FEDER) [CD13/00074 to V.P., PI15/00378 and PIE15/00028 to R.M., FIS PI17/01246, RD12/0036/0071 and FIS PI14/00450 to J.S., RD12/0036/0069 to M.G.., ISCIII-PS13/1640 and PI16/0665 to E.B., and RD12/0036/0014 and PIE13/00046 to M.A.S.] CIBERONC [CB16/12/00284 to M.A.S.]; CIBER-BBN [CBV6/01/1031 and Nanomets3 to R.M.]; AGAUR [2017 FI_B 00680 to A.F.; 2017-SGR-865 and 2014PROD0005 to R.M. and 2014-SGR-1281 to J.S.]; Fundació La Marató TV3 [416/C/2013-2030 to R.M., 100830/31/32 to J.S., M.G.. and M.A.S.]; Josep Carreras Leukemia Research Institute [P/AG 2017 to R.M.]; Spanish Health Research Program [PI12/02321 to M.G..]; Spanish Association Against Cancer (AECC) [to M.C.C.]; a grant from the Cellex Foundation, Barcelona [to J.S.]; a grant from La Generalitat de Catalunya (PERIS) [SLT002/16/00433 to J.S.]; and a grant from Fundación Española de Hematología y Hemoterapia (FEHH) [to V.P.]
Multicenter phase II study of matured dendritic cells pulsed with melanoma cell line lysates in patients with advanced melanoma
<p>Abstract</p> <p>Background</p> <p>Several single center studies have provided evidence of immune activation and antitumor activity of therapeutic vaccination with dendritic cells (DC) in patients with metastatic melanoma. The efficacy of this approach in patients with favorable prognosis metastatic melanoma limited to the skin, subcutaneous tissues and lung (stages IIIc, M1a, M1b) was tested in a multicenter two stage phase 2 study with centralized DC manufacturing.</p> <p>Methods</p> <p>The vaccine (IDD-3) consisted 8 doses of autologous monocyte-derived matured DC generated in serum-free medium with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-13 (IL-13), pulsed with lysates of three allogeneic melanoma cell lines, and matured with interferon gamma. The primary endpoint was antitumor activity.</p> <p>Results</p> <p>Among 33 patients who received IDD-3 there was one complete response (CR), two partial responses (PR), and six patients had stable disease (SD) lasting more than eight weeks. The overall prospectively defined tumor growth control rate was 27% (90% confidence interval of 13-46%). IDD-3 administration had minimal toxicity and it resulted in a high frequency of immune activation to immunizing melanoma antigens as assessed by <it>in vitro </it>immune monitoring assays.</p> <p>Conclusions</p> <p>The administration of matured DC loaded with tumor lysates has significant immunogenicity and antitumor activity in patients with limited metastatic melanoma.</p> <p>Clinical trial registration</p> <p>NCT00107159.</p
The APOKASC Catalog: An Asteroseismic and Spectroscopic Joint Survey of Targets in the Kepler Fields
We present the first APOKASC catalog of spectroscopic and asteroseismic
properties of 1916 red giants observed in the Kepler fields. The spectroscopic
parameters provided from the Apache Point Observatory Galactic Evolution
Experiment project are complemented with asteroseismic surface gravities,
masses, radii, and mean densities determined by members of the Kepler
Asteroseismology Science Consortium. We assess both random and systematic
sources of error and include a discussion of sample selection for giants in the
Kepler fields. Total uncertainties in the main catalog properties are of order
80 K in Teff , 0.06 dex in [M/H], 0.014 dex in log g, and 12% and 5% in mass
and radius, respectively; these reflect a combination of systematic and random
errors. Asteroseismic surface gravities are substantially more precise and
accurate than spectroscopic ones, and we find good agreement between their mean
values and the calibrated spectroscopic surface gravities. There are, however,
systematic underlying trends with Teff and log g. Our effective temperature
scale is between 0-200 K cooler than that expected from the Infrared Flux
Method, depending on the adopted extinction map, which provides evidence for a
lower value on average than that inferred for the Kepler Input Catalog (KIC).
We find a reasonable correspondence between the photometric KIC and
spectroscopic APOKASC metallicity scales, with increased dispersion in KIC
metallicities as the absolute metal abundance decreases, and offsets in Teff
and log g consistent with those derived in the literature. We present mean
fitting relations between APOKASC and KIC observables and discuss future
prospects, strengths, and limitations of the catalog data.Comment: 49 pages. ApJSupp, in press. Full machine-readable ascii files
available under ancillary data. Categories: Kepler targets, asteroseismology,
large spectroscopic survey
A Cautionary Tale: MARVELS Brown Dwarf Candidate Reveals Itself To Be A Very Long Period, Highly Eccentric Spectroscopic Stellar Binary
We report the discovery of a highly eccentric, double-lined spectroscopic
binary star system (TYC 3010-1494-1), comprising two solar-type stars that we
had initially identified as a single star with a brown dwarf companion. At the
moderate resolving power of the MARVELS spectrograph and the spectrographs used
for subsequent radial-velocity (RV) measurements (R ~ <30,000), this particular
stellar binary mimics a single-lined binary with an RV signal that would be
induced by a brown dwarf companion (Msin(i)~50 M_Jup) to a solar-type primary.
At least three properties of this system allow it to masquerade as a single
star with a very low-mass companion: its large eccentricity (e~0.8), its
relatively long period (P~238 days), and the approximately perpendicular
orientation of the semi-major axis with respect to the line of sight (omega~189
degrees). As a result of these properties, for ~95% of the orbit the two sets
of stellar spectral lines are completely blended, and the RV measurements based
on centroiding on the apparently single-lined spectrum is very well fit by an
orbit solution indicative of a brown dwarf companion on a more circular orbit
(e~0.3). Only during the ~5% of the orbit near periastron passage does the
true, double-lined nature and large RV amplitude of ~15 km/s reveal itself. The
discovery of this binary system is an important lesson for RV surveys searching
for substellar companions; at a given resolution and observing cadence, a
survey will be susceptible to these kinds of astrophysical false positives for
a range of orbital parameters. Finally, for surveys like MARVELS that lack the
resolution for a useful line bisector analysis, it is imperative to monitor the
peak of the cross-correlation function for suspicious changes in width or
shape, so that such false positives can be flagged during the candidate vetting
process.Comment: 16 pages, 11 figures, 6 table
Recommended from our members
Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma
Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model
- …