Divertor detachment offers a promising solution to the challenge of plasma-wall interactions for steady-state operation of fusion reactors. Here, we demonstrate the excellent compatibility of ...actively controlled full divertor detachment with a high-performance (β
~ 3, H
~ 1.5) core plasma, using high-β
(poloidal beta, β
> 2) scenario characterized by a sustained core internal transport barrier (ITB) and a modest edge transport barrier (ETB) in DIII-D tokamak. The high-β
high-confinement scenario facilitates divertor detachment which, in turn, promotes the development of an even stronger ITB at large radius with a weaker ETB. This self-organized synergy between ITB and ETB, leads to a net gain in energy confinement, in contrast to the net confinement loss caused by divertor detachment in standard H-modes. These results show the potential of integrating excellent core plasma performance with an efficient divertor solution, an essential step towards steady-state operation of reactor-grade plasmas.
Supernova (SN) H0pe was discovered as a new transient in
James Webb
Space Telescope (JWST) NIRCam images of the galaxy cluster
PLCK G165.7+67.0
taken as part of the Prime Extragalactic Areas for ...Reionization and Lensing Science (PEARLS) JWST GTO program (ID 1176) on 2023 March 30. The transient is a compact source associated with a background galaxy that is stretched and triply imaged by the strong gravitational lensing of the cluster. This paper reports spectra in the 950–1370 nm observer frame of two of the galaxy images obtained with Large Binocular Telescope (LBT) Utility Camera in the Infrared (LUCI) in long-slit mode two weeks after the JWST observations. The individual and average spectra show the O
II
λλ
3727,3730 doublet and the Balmer and 4000 Å breaks at redshift
z
= 1.783 ± 0.002. The code investigating galaxy emission (CIGALE) best-fit model of the spectral energy distribution indicates that the host galaxy of SN H0pe is massive (
M
star
≃ 6 × 10
10
M
⊙
after correcting for a magnification factor
μ
∼ 7) with a predominantly intermediate-age (∼2 Gyr) stellar population, moderate extinction, and a magnification-corrected star formation rate ≃13
M
⊙
yr
−1
, consistent with being below the main sequence of star formation. These properties suggest that H0pe might be a type Ia SN. Additional observations of SN H0pe and its host recently carried out with JWST (JWST-DD-4446; PI: B. Frye) will be able to both determine the SN classification and confirm its association with the galaxy analyzed in this work.
Characterising connectivity between geographically separated biological populations is a common goal in many fields. Recent approaches to understanding connectivity between malaria parasite ...populations, with implications for disease control efforts, have used estimates of relatedness based on identity-by-descent (IBD). However, uncertainty around estimated relatedness has not been accounted for. IBD-based relatedness estimates with uncertainty were computed for pairs of monoclonal Plasmodium falciparum samples collected from five cities on the Colombian-Pacific coast where long-term clonal propagation of P. falciparum is frequent. The cities include two official ports, Buenaventura and Tumaco, that are separated geographically but connected by frequent marine traffic. Fractions of highly-related sample pairs (whose classification using a threshold accounts for uncertainty) were greater within cities versus between. However, based on both highly-related fractions and on a threshold-free approach (Wasserstein distances between parasite populations) connectivity between Buenaventura and Tumaco was disproportionally high. Buenaventura-Tumaco connectivity was consistent with transmission events involving parasites from five clonal components (groups of statistically indistinguishable parasites identified under a graph theoretic framework). To conclude, P. falciparum population connectivity on the Colombian-Pacific coast abides by accessibility not isolation-by-distance, potentially implicating marine traffic in malaria transmission with opportunities for targeted intervention. Further investigations are required to test this hypothesis. For the first time in malaria epidemiology (and to our knowledge in ecological and epidemiological studies more generally), we account for uncertainty around estimated relatedness (an important consideration for studies that plan to use genotype versus whole genome sequence data to estimate IBD-based relatedness); we also use threshold-free methods to compare parasite populations and identify clonal components. Threshold-free methods are especially important in analyses of malaria parasites and other recombining organisms with mixed mating systems where thresholds do not have clear interpretation (e.g. due to clonal propagation) and thus undermine the cross-comparison of studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The human malaria parasite Plasmodium falciparum is globally widespread, but its prevalence varies significantly between and even within countries. Most population genetic studies in P. falciparum ...focus on regions of high transmission where parasite populations are large and genetically diverse, such as sub-Saharan Africa. Understanding population dynamics in low transmission settings, however, is of particular importance as these are often where drug resistance first evolves. Here, we use the Pacific Coast of Colombia and Ecuador as a model for understanding the population structure and evolution of Plasmodium parasites in small populations harboring less genetic diversity. The combination of low transmission and a high proportion of monoclonal infections means there are few outcrossing events and clonal lineages persist for long periods of time. Yet despite this, the population is evolutionarily labile and has successfully adapted to changes in drug regime. Using newly sequenced whole genomes, we measure relatedness between 166 parasites, calculated as identity by descent (IBD), and find 17 distinct but highly related clonal lineages, six of which have persisted in the region for at least a decade. This inbred population structure is captured in more detail with IBD than with other common population structure analyses like PCA, ADMIXTURE, and distance-based trees. We additionally use patterns of intra-chromosomal IBD and an analysis of haplotypic variation to explore past selection events in the region. Two genes associated with chloroquine resistance, crt and aat1, show evidence of hard selective sweeps, while selection appears soft and/or incomplete at three other key resistance loci (dhps, mdr1, and dhfr). Overall, this work highlights the strength of IBD analyses for studying parasite population structure and resistance evolution in regions of low transmission, and emphasizes that drug resistance can evolve and spread in small populations, as will occur in any region nearing malaria elimination.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Through the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n=3334), SF3B1 (n=2322), TP53 (n=2309), ...MYD88 (n=1080) and BIRC3 (n=919) genes, mainly at diagnosis (75%) and before treatment (>90%). BIRC3 mutations (2.5%) were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12, whereas MYD88 mutations (2.2%) were exclusively found among M-CLL. NOTCH1, SF3B1 and TP53 exhibited variable frequencies and were mostly enriched within clinically aggressive cases. Interestingly, as the timespan between diagnosis and mutational screening increased, so too did the incidence of SF3B1 mutations; no such increase was observed for NOTCH1 mutations. Regarding the clinical impact, NOTCH1 mutations, SF3B1 mutations and TP53 aberrations (deletion/mutation, TP53ab) correlated with shorter time-to-first-treatment (P<0.0001) in 889 treatment-naive Binet stage A cases. In multivariate analysis (n=774), SF3B1 mutations and TP53ab along with del(11q) and U-CLL, but not NOTCH1 mutations, retained independent significance. Importantly, TP53ab and SF3B1 mutations had an adverse impact even in U-CLL. In conclusion, we support the clinical relevance of novel recurrent mutations in CLL, highlighting the adverse impact of SF3B1 and TP53 mutations, even independent of IGHV mutational status, thus underscoring the need for urgent standardization/harmonization of the detection methods.
Abstract A bright ( m F150W,AB = 24 mag), z = 1.95 supernova (SN) candidate was discovered in JWST/NIRCam imaging acquired on 2023 November 17. The SN is quintuply imaged as a result of strong ...gravitational lensing by a foreground galaxy cluster, detected in three locations, and remarkably is the second lensed SN found in the same host galaxy. The previous lensed SN was called “Requiem,” and therefore the new SN is named “Encore.” This makes the MACS J0138.0−2155 cluster the first known system to produce more than one multiply imaged SN. Moreover, both SN Requiem and SN Encore are Type Ia SNe (SNe Ia), making this the most distant case of a galaxy hosting two SNe Ia. Using parametric host fitting, we determine the probability of detecting two SNe Ia in this host galaxy over a ∼10 yr window to be ≈3%. These observations have the potential to yield a Hubble constant ( H 0 ) measurement with ∼10% precision, only the third lensed SN capable of such a result, using the three visible images of the SN. Both SN Requiem and SN Encore have a fourth image that is expected to appear within a few years of ∼2030, providing an unprecedented baseline for time-delay cosmography.
First-generation somatostatin analogs (SSAs), such as octreotide (OCT), are the first line medical therapy for acromegaly. Pasireotide (PAS), a newly developed SSA, has shown promising results in the ...treatment of acromegaly.
To compare the antisecretory effect of OCT and PAS in primary cultures of growth hormone (GH)-secreting pituitary adenomas (GH-omas). To correlate responses with the adenoma somatostatin receptor (SSTR) profile.
The effect of OCT and PAS on GH (and PRL) secretion was tested in 33 GH-oma cultures. SSTR expression was evaluated in adenoma samples.
Patients with acromegaly referred to the Erasmus Medical Center (Rotterdam, The Netherlands).
OCT and PAS treatment for 72 hours (10 nM).
GH (and PRL) concentrations in cell culture media. SSTR expression in adenoma samples.
The overall effect of OCT (-36.8%) and PAS (-37.1%) on GH secretion was superimposable. We identified three adenoma groups: PAS+ (PAS more effective than OCT), n = 6; PAS = OCT, n = 22; and OCT+ (OCT more effective than PAS), n = 5. PAS+ adenomas showed lower somatostatin receptor subtype (sst)2 messenger RNA (mRNA) and sst2/sst5 mRNA ratio, compared with the other groups (P < 0.05). PAS inhibited PRL hypersecretion more than OCT (P < 0.01).
Overall, OCT and PAS equally reduced GH secretion in vitro. Adenomas with lower sst2 mRNA expression and lower sst2/sst5 mRNA ratio were better responders to PAS compared with OCT. SSTR evaluation in GH-omas may become a tool for tailored SSA treatment in acromegaly.
We report the discovery of Mothra, an extremely magnified monster star, likely a binary system of two supergiant stars, in one of the strongly lensed galaxies behind the galaxy cluster MACS ...J0416.1−2403. Mothra is in a galaxy with spectroscopic redshift
z
= 2.091 in a portion of the galaxy that is parsecs away from the cluster caustic. The binary star is observed only on the side of the critical curve with negative parity but has been detectable for at least eight years, implying the presence of a small lensing perturber. Microlenses alone cannot explain the earlier observations of this object made with the
Hubble
Space Telescope. A larger perturber with a mass of at least 10
4
M
⊙
offers a more satisfactory explanation. Based on the lack of perturbation on other nearby sources in the same arc, the maximum mass of the perturber is 2.5 × 10
6
M
⊙
, making this the smallest substructure constrained by lensing at
z
> 0.3. The existence of this millilens is fully consistent with expectations from standard cold dark matter cosmology. On the other hand, the existence of such a small substructure in a cluster environment has implications for other dark matter models. In particular, warm dark matter models with particle masses below 8.7 keV are excluded by our observations. Similarly, axion dark matter models are consistent with the observations only if the axion mass is in the range 0.5 × 10
−22
eV <
m
a
< 5 × 10
−22
eV.
Calcium looping, CaL, is rapidly developing as a postcombustion CO2 capture technology because its similarity to existing power plants using circulating fluidized bed combustors, CFBC. In this work ...we present experimental results from a pilot built to demonstrate the concept at the MWth scale. The pilot plant treats 1/150 of the flue gases of an existing CFBC power plant ("la Pereda") and it has been operated in steady state for hundreds of hours of accumulated experimental time. The pilot includes two 15 m height interconnected circulating fluidized bed reactors: a CO2 absorber (or carbonator of CaO) and a continuous CaCO3 calciner operated as an oxy-fuel CFBC. Operating conditions in the reactors are resembling those expected in large CaL CO2 capture systems in terms of reactor temperatures, gas velocities, solid compositions and circulation rates and reaction atmospheres. The evolution of CO2 capture efficiencies and solid properties (CO2 carrying capacity and CaO conversion to CaCO3 and CaSO4) have been studied as a function of key operating conditions. It is demonstrated that CO2 capture efficiencies over 90% are feasible with a supply of active CaO slightly over the molar flow of CO2 entering the carbonator. Closure of carbon and sulphur balances has been satisfactory during steady state periods. A basic reactor model developed from smaller test facilities seems to provide a reasonable interpretation of the observed trends. This should facilitate the further scale up of this new technology.
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