The ^{24}Mg + ^{24}Mg reaction has been studied at the Legnaro Tandem at a CM bombarding energy of 45.7 MeV where a narrow and high spin resonance has been reported previously. The decay of the ...resonance into the inelastic and fusion–evaporation channels has been investigated. The ON and OFF resonance decay yields have been measured using, for the inelastic channels, the fragment spectrometer PRISMA and the γ array CLARA, and, for the fusion–evaporation channels, the Si array EUCLIDES and the γ array GASP. Strong resonant effects have been observed in the inelastic channels involving the 2_1^+ and 4_1^+ states of the ^{24}Mg ground state band. Weaker effects are also seen in certain fusion–evaporation channels. The properties of the studied resonance are in agreement with molecular model predictions. It is also proposed that the narrow and high spin ^{24}Mg + ^{24}Mg resonance corresponds to the formation of a fast rotating and highly prolate deformed ^{48}Cr after a Jacobi shape transition and just before fission.
We previously utilized a Sleeping Beauty (SB) transposon mutagenesis screen to discover novel drivers of HCC. This approach identified recurrent mutations within the Dlk1-Dio3 imprinted domain, ...indicating that alteration of one or more elements within the domain provides a selective advantage to cells during the process of hepatocarcinogenesis. For the current study, we performed transcriptome and small RNA sequencing to profile gene expression in SB-induced HCCs in an attempt to clarify the genetic element(s) contributing to tumorigenesis. We identified strong induction of Retrotransposon-like 1 (Rtl1) expression as the only consistent alteration detected in all SB-induced tumors with Dlk1-Dio3 integrations, suggesting that Rtl1 activation serves as a driver of HCC. While previous studies have identified correlations between disrupted expression of multiple Dlk1-Dio3 domain members and HCC, we show here that direct modulation of a single domain member, Rtl1, can promote hepatocarcinogenesis in vivo. Overexpression of Rtl1 in the livers of adult mice using a hydrodynamic gene delivery technique resulted in highly penetrant (86%) tumor formation. Additionally, we detected overexpression of RTL1 in 30% of analyzed human HCC samples, indicating the potential relevance of this locus as a therapeutic target for patients. The Rtl1 locus is evolutionarily derived from the domestication of a retrotransposon. In addition to identifying Rtl1 as a novel driver of HCC, our study represents one of the first direct in vivo demonstrations of a role for such a co-opted genetic element in promoting carcinogenesis.
Asteroseismology probes the internal structures of stars by using their natural pulsation frequencies
. It relies on identifying sequences of pulsation modes that can be compared with theoretical ...models, which has been done successfully for many classes of pulsators, including low-mass solar-type stars
, red giants
, high-mass stars
and white dwarfs
. However, a large group of pulsating stars of intermediate mass-the so-called δ Scuti stars-have rich pulsation spectra for which systematic mode identification has not hitherto been possible
. This arises because only a seemingly random subset of possible modes are excited and because rapid rotation tends to spoil regular patterns
. Here we report the detection of remarkably regular sequences of high-frequency pulsation modes in 60 intermediate-mass main-sequence stars, which enables definitive mode identification. The space motions of some of these stars indicate that they are members of known associations of young stars, as confirmed by modelling of their pulsation spectra.
Valvular calcification is central to the pathogenesis and progression of aortic stenosis, with preclinical and observational studies suggesting that bone turnover and osteoblastic differentiation of ...valvular interstitial cells are important contributory mechanisms. We aimed to establish whether inhibition of these pathways with denosumab or alendronic acid could reduce disease progression in aortic stenosis.
In a single-center, parallel group, double-blind randomized controlled trial, patients >50 years of age with calcific aortic stenosis (peak aortic jet velocity >2.5 m/s) were randomized 2:1:2:1 to denosumab (60 mg every 6 months), placebo injection, alendronic acid (70 mg once weekly), or placebo capsule. Participants underwent serial assessments with Doppler echocardiography, computed tomography aortic valve calcium scoring, and
F-sodium fluoride positron emission tomography and computed tomography. The primary end point was the calculated 24-month change in aortic valve calcium score.
A total of 150 patients (mean age, 72±8 years; 21% women) with calcific aortic stenosis (peak aortic jet velocity, 3.36 m/s 2.93-3.82 m/s; aortic valve calcium score, 1152 AU 655-2065 AU) were randomized and received the allocated trial intervention: denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25; pooled for analysis). Serum C-terminal telopeptide, a measure of bone turnover, halved from baseline to 6 months with denosumab (0.23 0.18-0.33 µg/L to 0.11 µg/L 0.08-0.17 µg/L) and alendronic acid (0.20 0.14-0.28 µg/L to 0.09 µg/L 0.08-0.13 µg/L) but was unchanged with placebo (0.23 0.17-0.30 µg/L to 0.26 µg/L 0.16-0.31 µg/L). There were no differences in 24-month change in aortic valve calcium score between denosumab and placebo (343 198-804 AU versus 354 AU 76-675 AU; P=0.41) or alendronic acid and placebo (326 138-813 AU versus 354 AU 76-675 AU;
=0.49). Similarly, there were no differences in change in peak aortic jet velocity or
F-sodium fluoride aortic valve uptake.
Neither denosumab nor alendronic acid affected progression of aortic valve calcification in patients with calcific aortic stenosis. Alternative pathways and mechanisms need to be explored to identify disease-modifying therapies for the growing population of patients with this potentially fatal condition. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02132026.
Cytogenetic studies of a small number of renal oncocytomas have indicated that loss of chromosomes 1 and Y may be involved in the pathogenesis of this tumor. To evaluate these observations further we ...selected paraffin embedded renal oncocytoma specimens from 20 male and 10 female patients for fluorescence in situ hybridization analysis.
Isolated nuclei were prepared from paraffin embedded specimens, and fluorescence in situ hybridization was performed with enumeration probes for chromosomes 1, 12, × and Y.
Tumors from 10 male (50 percent) and 4 female (40 percent) patients demonstrated chromosomal alterations. Loss of chromosome Y was observed in specimens from all 10 male patients, and loss of chromosome 1 or gain of chromosome 12 was noted in 5 and 2 of these specimens, respectively. Of the 4 female patients with chromosomal abnormalities 2 had loss of chromosome 1, 1 had gain of chromosome 1 and 1 had gain of chromosome 12.
Our results confirm that loss of chromosomes Y and 1 is common in renal oncocytoma, and that the alterations are probably involved in the pathogenesis of this tumor.
The study of nuclei in the region around the N = Z doubly-magic nucleus 100 Sn has been of long standing interest for the nuclear structure and nuclear astrophysics. Recently, Park et al. have ...reported on properties of γ-decaying isomers and isomeric ratios in the vicinity of 100 Sn. That experiment was performed at the Radioactive Ion Beam Factory (RIBF) of the RIKEN Nishina Center in Japan as a part of the EURICA campaign. Neutron-deficient nuclei were produced in a fragmentation reaction of a 124 Xe primary beam on a 9 Be target at an energy of 345 MeV/A. Secondary ions were separated and identified in the BigRIPS fragment separator and implanted in the silicon detector array WAS3ABi. The data presented here were obtained in another experiment performed at the RIBF using the same reaction but slightly different separator settings. New results of ratios of isomeric population and half-lives of γ-decaying isomers populated in the experiment are presented.
Abstract Antimicrobial susceptibility testing (AST) is indicated for pathogens contributing to an infectious process that warrants antimicrobial therapy if susceptibility to antimicrobials cannot be ...predicted reliably based on knowledge of their identity. Such tests are most frequently used when the etiologic agents are members of species capable of demonstrating resistance to commonly prescribed antibiotics. Some organisms have predictable susceptibility to antimicrobial agents (ie, Streptococcus pyogenes to penicillin), and empirical therapy for these organisms is typically used. Therefore, AST for such pathogens is seldom required or performed. In addition, AST is valuable in evaluating the activity of new and experimental compounds and investigating the epidemiology of antimicrobial resistant pathogens. Several laboratory methods are available to characterize the in vitro susceptibility of bacteria to antimicrobial agents. When the nature of the infection is unclear and the culture yields mixed growth or usual microbiota (wherein the isolates usually bear little relationship to the actual infectious process), AST is usually unnecessary and results may, in fact, be dangerously misleading. Phenotypic methods for detection of specific antimicrobial resistance mechanisms are increasingly being used to complement AST (ie, inducible clindamycin resistance among several gram-positive bacteria) and to provide clinicians with preliminary direction for antibiotic selection pending results generated from standardized AST (ie, β-lactamase tests). In addition, molecular methods are being developed and incorporated by microbiology laboratories into resistance detection algorithms for rapid, sensitive assessment of carriage states of epidemiologically and clinically important pathogens, often directly from clinical specimens (ie, presence of vancomycin-resistant enterococci in fecal specimens).
Acute exacerbation of idiopathic pulmonary fibrosis has been defined as an acute, clinically significant, respiratory deterioration of unidentifiable cause. The objective of this international ...working group report on acute exacerbation of idiopathic pulmonary fibrosis was to provide a comprehensive update on the topic. A literature review was conducted to identify all relevant English text publications and abstracts. Evidence-based updates on the epidemiology, etiology, risk factors, prognosis, and management of acute exacerbations of idiopathic pulmonary fibrosis are provided. Finally, to better reflect the current state of knowledge and improve the feasibility of future research into its etiology and treatment, the working group proposes a new conceptual framework for acute respiratory deterioration in idiopathic pulmonary fibrosis and a revised definition and diagnostic criteria for acute exacerbation of idiopathic pulmonary fibrosis.
Background: A recent inelastic alpha-scattering experiment Phys. Rev. Lett.
129, 102701 (2022) found $0^+$ resonances in $^{24}$Mg on and above the
$^{12}$C+$^{12}$C break-up threshold. It has been ...conjectured that the states
have a $^{12}$C+$^{12}$C cluster structure, and play a similar role in
accelerating $^{12}$C+$^{12}$C fusion to the manner in which the Hoyle state
accelerates production of $^{12}$C in massive stars.
Purpose: We wish to build up a quantitative theoretical basis for the
considerations of the Hoyle-state paradigm, by calculating the distribution of
the $0^+$ states in the shell, as well as in the relevant cluster models.
Methods: We determine the spectrum of excited $0^+$ states in $^{24}$Mg
nucleus using multiconfigurational dynamical symmetry calculations leading to a
unified description of the quartet (or shell), $^{12}$C+$^{12}$C and
$^{20}$Ne+$^{4}$He cluster configurations.
Results: The density of $0^+$ states in the quartet spectrum is comparable to
that found in experiment; however, the density of cluster states is
considerably less.
Conclusions: The recently observed alpha-scattering resonances do not seem to
be simple $^{12}$C+$^{12}$C cluster states, but are more plausibly interpreted
as fragmented cluster states due to coupling to quartet excitations, as
background states.
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