Illness associated with Respiratory Syncytial Virus (RSV) remains an unmet medical need in both full-term infants and older adults. The fusion glycoprotein (F) of RSV, which plays a key role in RSV ...infection and is a target of neutralizing antibodies, is an attractive vaccine target for inducing RSV-specific immunity.
BALB/c mice and cotton rats, two well-characterized rodent models of RSV infection, were used to evaluate the immunogenicity of intramuscularly administered RSV vaccine candidates consisting of purified soluble F (sF) protein formulated with TLR4 agonist glucopyranosyl lipid A (GLA), stable emulsion (SE), GLA-SE, or alum adjuvants. Protection from RSV challenge, serum RSV neutralizing responses, and anti-F IgG responses were induced by all of the tested adjuvanted RSV sF vaccine formulations. However, only RSV sF + GLA-SE induced robust F-specific TH1-biased humoral and cellular responses. In mice, these F-specific cellular responses include both CD4 and CD8 T cells, with F-specific polyfunctional CD8 T cells that traffic to the mouse lung following RSV challenge. This RSV sF + GLA-SE vaccine formulation can also induce robust RSV neutralizing titers and prime IFNγ-producing T cell responses in Sprague Dawley rats.
These studies indicate that a protein subunit vaccine consisting of RSV sF + GLA-SE can induce robust neutralizing antibody and T cell responses to RSV, enhancing viral clearance via a TH1 immune-mediated mechanism. This vaccine may benefit older populations at risk for RSV disease.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ABSTRACT
Only a few wide-orbit planets around old stars have been detected, which limits our statistical understanding of this planet population. Following the systematic search for planetary ...anomalies in microlensing events found by the Korea Microlensing Telescope Network, we present the discovery and analysis of three events that were initially thought to contain wide-orbit planets. The anomalous feature in the light curve of OGLE-2018-BLG-0383 is caused by a planet with mass ratio q = 2.1 × 10−4 and a projected separation s = 2.45. This makes it the lowest mass-ratio microlensing planet at such wide orbits. The other two events, KMT-2018-BLG-0998 and OGLE-2018-BLG-0271, are shown to be stellar binaries (q > 0.1) with rather close (s < 1) separations. We briefly discuss the properties of known wide-orbit microlensing planets and show that the survey observations are crucial in discovering and further statistically constraining such a planet population.
Aims.
We announce the discovery of a microlensing planetary system, in which a sub-Saturn planet is orbiting an ultracool dwarf host.
Methods.
We detected the planetary system by analyzing the ...short-timescale (
t
E
~ 4.4 days) lensing event KMT-2018-BLG-0748. The central part of the light curve exhibits asymmetry due to negative deviations in the rising side and positive deviations in the falling side.
Results.
We find that the deviations are explained by a binary-lens model with a mass ratio between the lens components of
q
~ 2 × 10
−3
. The short event timescale, together with the small angular Einstein radius,
θ
E
~ 0.11 mas, indicate that the mass of the planet host is very small. The Bayesian analysis conducted under the assumption that the planet frequency is independent of the host mass indicates that the mass of the planet is
M
p
= 0.18
−0.10
+0.29
M
J
, and the mass of the host,
M
h
= 0.087
−0.047
+0.138
M
⊙
, is near the star–brown dwarf boundary, but the estimated host mass is sensitive to this assumption about the planet hosting probability. High-resolution follow-up observations would lead to revealing the nature of the planet host.
Full text
Available for:
FMFMET, NUK, UL, UM, UPUK
High-cadence observations of the Galactic bulge by the microlensing surveys led to the discovery of a handful of extremely short-timescale microlensing events that can be attributed to free-floating ...or wide-orbit planets. Here, we report the discovery of another strong free-floating planet candidate, which was found from the analysis of the gravitational microlensing event OGLE-2019-BLG-0551. The light curve of the event is characterized by a very short duration ( 3 days) and a very small amplitude ( 0.1 mag). From modeling of the light curve, we find that the Einstein timescale, day, is much shorter, and the angular Einstein radius, as, is much smaller than those of typical lensing events produced by stellar-mass lenses ( days, mas), indicating that the lens is very likely to be a planetary-mass object. We conduct an extensive search for possible signatures of a companion star in the light curve of the event, finding no significant evidence for the putative host star. For the first time, we also demonstrate that the angular Einstein radius of the lens does not depend on blending in the low-magnification events with strong finite source effects.
Intragenic copy-number variants (CNVs) contribute to the allelic spectrum of both Mendelian and complex disorders. Although pathogenic deletions and duplications in SPAST (mutations in which cause ...autosomal-dominant spastic paraplegia 4 SPG4) have been described, their origins and molecular consequences remain obscure. We mapped breakpoint junctions of 54 SPAST CNVs at nucleotide resolution. Diverse combinations of exons are deleted or duplicated, highlighting the importance of particular exons for spastin function. Of the 54 CNVs, 38 (70%) appear to be mediated by an Alu-based mechanism, suggesting that the Alu-rich genomic architecture of SPAST renders this locus susceptible to various genome rearrangements. Analysis of breakpoint Alus further informs a model of Alu-mediated CNV formation characterized by small CNV size and potential involvement of mechanisms other than homologous recombination. Twelve deletions (22%) overlap part of SPAST and a portion of a nearby, directly oriented gene, predicting novel chimeric genes in these subjects’ genomes. cDNA from a subject with a SPAST final exon deletion contained multiple SPAST:SLC30A6 fusion transcripts, indicating that SPAST CNVs can have transcriptional effects beyond the gene itself. SLC30A6 has been implicated in Alzheimer disease, so these fusion gene data could explain a report of spastic paraplegia and dementia cosegregating in a family with deletion of the final exon of SPAST. Our findings provide evidence that the Alu genomic architecture of SPAST predisposes to diverse CNV alleles with distinct transcriptional—and possibly phenotypic—consequences. Moreover, we provide further mechanistic insights into Alu-mediated copy-number change that are extendable to other loci.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aims.
We reexamine high-magnification microlensing events in the previous data collected by the KMTNet survey with the aim of finding planetary signals that were not noticed before. In this work, we ...report the planetary system KMT-2018-BLG-1988L, which was found from this investigation.
Methods.
The planetary signal appears as a deviation with ≲0.2 mag from a single-lens light curve and lasted for about 6 h. The deviation exhibits a pattern of a dip surrounded by weak bumps on both sides of the dip. The analysis of the lensing light curve indicates that the signal is produced by a low-mass-ratio (
q
~ 4 × 10
−5
) planetary companion located near the Einstein ring of the host star.
Results.
The mass of the planet, M
planet
= 6.8
−3.5
+4.7
M
⊕
and 5.6
−2.8
+3.8
M
⊕
for the two possible solutions, estimated from the Bayesian analysis indicates that the planet is in the regime of a super-Earth. The host of the planet is a disk star with a mass of M
host
= 0.47
−0.25
+0.33
M
⊙
and a distance of D
L
= 4.2
−.14
+1.8
kpc. KMT-2018-BLG-1988Lb is the 18th known microlensing planet with a mass below the upper limit of a super-Earth. The fact that 15 out of the 18 known microlensing planets with masses ≲10
M
⊕
were detected in the 5 yr following the full operation of the KMTNet survey indicates that the KMTNet database is an important reservoir of very low-mass planets.
Full text
Available for:
FMFMET, NUK, UL, UM, UPUK
Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. It presents similarly to spontaneous ...heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis after vaccination with the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson) have previously been described.
To describe surveillance data and reporting rates of all reported TTS cases after COVID-19 vaccination in the United States.
Case series.
United States.
Case patients receiving a COVID-19 vaccine from 14 December 2020 through 31 August 2021 with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction) reported to the Vaccine Adverse Event Reporting System. If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for antiplatelet factor 4 antibodies or functional heparin-induced thrombocytopenia platelet test result was required.
Reporting rates (cases per million vaccine doses) and descriptive epidemiology.
A total of 57 TTS cases were confirmed after vaccination with Ad26.COV2.S (
= 54) or a messenger RNA (mRNA)-based COVID-19 vaccine (
= 3). Reporting rates for TTS were 3.83 per million vaccine doses (Ad26.COV2.S) and 0.00855 per million vaccine doses (mRNA-based COVID-19 vaccines). The median age of patients with TTS after Ad26.COV2.S vaccination was 44.5 years (range, 18 to 70 years), and 69% of patients were women. Of the TTS cases after mRNA-based COVID-19 vaccination, 2 occurred in men older than 50 years and 1 in a woman aged 50 to 59 years. All cases after Ad26.COV2.S vaccination involved hospitalization, including 36 (67%) with intensive care unit admission. Outcomes of hospitalizations after Ad26.COV2.S vaccination included death (15%), discharge to postacute care (17%), and discharge home (68%).
Underreporting and incomplete case follow-up.
Thrombosis with thrombocytopenia syndrome is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the 3 cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate.
Centers for Disease Control and Prevention.
Aims.
We analyze the microlensing event KMT-2019-BLG-0797. The light curve of the event exhibits two anomalous features from a single-lens single-source model, and we aim to reveal the nature of the ...anomaly.
Methods.
It is found that a model with two lenses plus a single source (2L1S model) can explain one feature of the anomaly, but the other feature cannot be explained. We test various models and find that both anomalous features can be explained by introducing an extra source to a 2L1S model (2L2S model), making the event the third confirmed case of a 2L2S event, following MOA-2010-BLG-117 and OGLE-2016-BLG-1003. It is estimated that the extra source comprises ∼4% of the
I
-band flux from the primary source.
Results.
Interpreting the event is subject to a close–wide degeneracy. According to the close solution, the lens is a binary consisting of two brown dwarfs with masses (
M
1
,
M
2
) ∼ (0.034, 0.021)
M
⊙
, and it is located at a distance of
D
L
∼ 8.2 kpc. According to the wide solution, on the other hand, the lens is composed of an object at the star–brown dwarf boundary and an M dwarf with masses (
M
1
,
M
2
) ∼ (0.06, 0.33)
M
⊙
located at
D
L
∼ 7.7 kpc. The source is composed of a late G dwarf to early K dwarf primary and an early-to-mid M dwarf companion.
Full text
Available for:
FMFMET, NUK, UL, UM, UPUK
Abstract
We present the analyses of two microlensing events, OGLE-2018-BLG-0567 and OGLE-2018-BLG-0962. In both events, the short-lasting anomalies were densely and continuously covered by two ...high-cadence surveys. The light-curve modeling indicates that the anomalies are generated by source crossings over the planetary caustics induced by planetary companions to the hosts. The estimated planet/host separation (scaled to the angular Einstein radius
θ
E
) and mass ratio are (
s
,
q
× 10
3
) = (1.81 ± 0.02, 1.24 ± 0.07) and (
s
,
q
× 10
3
) = (1.25 ± 0.03, 2.38 ± 0.08), respectively. From Bayesian analyses, we estimate the host and planet masses as
(
M
h
,
M
p
)
=
(
0.25
−
0.13
+
0.27
M
⊙
,
0.32
−
0.17
+
0.34
M
J
)
and
(
M
h
,
M
p
)
=
(
0.54
−
0.28
+
0.33
M
⊙
,
1.34
−
0.70
+
0.82
M
J
)
, respectively. These planetary systems are located at a distance of
7.06
−
1.15
+
0.93
kpc
for OGLE-2018-BLG-0567 and
6.50
−
1.75
+
1.06
kpc
for OGLE-2018-BLG-0962, suggesting that they are likely to be near the Galactic bulge. The two events prove the capability of current high-cadence surveys for finding planets through the planetary-caustic channel. We find that most published planetary-caustic planets are found in Hollywood events in which the source size strongly contributes to the anomaly cross-section relative to the size of the caustic.
We report the discovery of a low-mass-ratio planet (q = 1.3 × 10−4), i.e., 2.5 times higher than the Neptune/Sun ratio. The planetary system was discovered from the analysis of the KMT-2017-BLG-0165 ...microlensing event, which has an obvious short-term deviation from the underlying light curve produced by the host of the planet. Although the fit improvement with the microlens parallax effect is relatively low, one component of the parallax vector is strongly constrained from the light curve, making it possible to narrow down the uncertainties of the lens physical properties. A Bayesian analysis yields that the planet has a super-Neptune mass orbiting a Sun-like star located at 4.5 kpc. The blended light is consistent with these host properties. The projected planet-host separation is , implying that the planet is located outside the snow line of the host, i.e., asl ∼ 2.1 au. KMT-2017-BLG-0165Lb is the sixteenth microlensing planet with mass ratio q < 3 × 10−4. Using the fifteen of these planets with unambiguous mass-ratio measurements, we apply a likelihood analysis to investigate the form of the mass-ratio function in this regime. If we adopt a broken power law for the form of this function, then the break is at qbr 0.55 × 10−4, which is much lower than previously estimated. Moreover, the change of the power-law slope, ζ > 3.3, is quite severe. Alternatively, the distribution is also suggestive of a pileup of planets at Neptune-like mass ratios, below which there is a dramatic drop in frequency.
PDF
