134 research outputs found
Pion and Kaon Distribution Amplitudes from lattice QCD: towards the continuum limit
We present the current status of a non-perturbative lattice calculation of
the moments of the pion and kaon distribution amplitudes by the RQCD
collaboration. Our investigation is carried out using dynamical,
non-perturbatively O(a)-improved Wilson fermions on the CLS ensembles with 5
different lattice spacings and pion masses down to the physical pion mass. A
combined continuum and chiral extrapolation to the physical point is performed
along two independent quark mass trajectories simultaneously. We employ
momentum smearing in order to decrease the contamination by excited states and
increase statistical precision.Comment: Proceedings of the 36th Annual International Symposium on Lattice
Field Theory - LATTICE201
Light-cone distribution amplitudes of octet baryons from lattice QCD
We present lattice QCD results for the wave function normalization constants
and the first moments of the distribution amplitudes for the lowest-lying
baryon octet. The analysis is based on a large number of ensembles
comprising multiple trajectories in the quark mass plane including physical
pion (and kaon) masses, large volumes, and, most importantly, five different
lattice spacings down to . This allows us to perform a
controlled extrapolation to the continuum and infinite volume limits by a
simultaneous fit to all available data. We demonstrate that the formerly
observed violation of flavor symmetry breaking constraints can, indeed, be
attributed to discretization effects that vanish in the continuum limit
Embryonic stem cell-specific microRNAs contribute to pluripotency by inhibiting regulators of multiple differentiation pathways
The findings that microRNAs (miRNAs) are essential for early development in many species and that embryonic miRNAs can reprogram somatic cells into induced pluripotent stem cells suggest that these miRNAs act directly on transcriptional and chromatin regulators of pluripotency. To elucidate the transcription regulatory networks immediately downstream of embryonic miRNAs, we extended the motif activity response analysis approach that infers the regulatory impact of both transcription factors (TFs) and miRNAs from genome-wide expression states. Applying this approach to multiple experimental data sets generated from mouse embryonic stem cells (ESCs) that did or did not express miRNAs of the ESC-specific miR-290-295 cluster, we identified multiple TFs that are direct miRNA targets, some of which are known to be active during cell differentiation. Our results provide new insights into the transcription regulatory network downstream of ESC-specific miRNAs, indicating that these miRNAs act on cell cycle and chromatin regulators at several levels and downregulate TFs that are involved in the innate immune respons
Incremental value of biomarker combinations to predict progression of mild cognitive impairment to Alzheimer’s dementia
Background The progression of mild cognitive impairment (MCI) to Alzheimer’s
disease (AD) dementia can be predicted by cognitive, neuroimaging, and
cerebrospinal fluid (CSF) markers. Since most biomarkers reveal complementary
information, a combination of biomarkers may increase the predictive power. We
investigated which combination of the Mini-Mental State Examination (MMSE),
Clinical Dementia Rating (CDR)-sum-of-boxes, the word list delayed free recall
from the Consortium to Establish a Registry of Dementia (CERAD) test battery,
hippocampal volume (HCV), amyloid-beta1–42 (Aβ42), amyloid-beta1–40 (Aβ40)
levels, the ratio of Aβ42/Aβ40, phosphorylated tau, and total tau (t-Tau)
levels in the CSF best predicted a short-term conversion from MCI to AD
dementia. Methods We used 115 complete datasets from MCI patients of the
“Dementia Competence Network”, a German multicenter cohort study with annual
follow-up up to 3 years. MCI was broadly defined to include amnestic and
nonamnestic syndromes. Variables known to predict progression in MCI patients
were selected a priori. Nine individual predictors were compared by receiver
operating characteristic (ROC) curve analysis. ROC curves of the five best
two-, three-, and four-parameter combinations were analyzed for significant
superiority by a bootstrapping wrapper around a support vector machine with
linear kernel. The incremental value of combinations was tested for
statistical significance by comparing the specificities of the different
classifiers at a given sensitivity of 85%. Results Out of 115 subjects, 28
(24.3%) with MCI progressed to AD dementia within a mean follow-up period of
25.5 months. At baseline, MCI-AD patients were no different from stable MCI in
age and gender distribution, but had lower educational attainment. All single
biomarkers were significantly different between the two groups at baseline.
ROC curves of the individual predictors gave areas under the curve (AUC)
between 0.66 and 0.77, and all single predictors were statistically superior
to Aβ40. The AUC of the two-parameter combinations ranged from 0.77 to 0.81.
The three-parameter combinations ranged from AUC 0.80–0.83, and the four-
parameter combination from AUC 0.81–0.82. None of the predictor combinations
was significantly superior to the two best single predictors (HCV and t-Tau).
When maximizing the AUC differences by fixing sensitivity at 85%, the two- to
four-parameter combinations were superior to HCV alone. Conclusion A
combination of two biomarkers of neurodegeneration (e.g., HCV and t-Tau) is
not superior over the single parameters in identifying patients with MCI who
are most likely to progress to AD dementia, although there is a gradual
increase in the statistical measures across increasing biomarker combinations.
This may have implications for clinical diagnosis and for selecting subjects
for participation in clinical trials
Pion distribution amplitude from Euclidean correlation functions: Exploring universality and higher-twist effects
Building upon our recent study [G. S. Bali et al., Eur. Phys. J. C 78, 217 (2018)], we investigate the feasibility of calculating the pion distribution amplitude from suitably chosen Euclidean correlation functions at large momentum. We demonstrate in this work the advantage of analyzing several correlation functions simultaneously and extracting the pion distribution amplitude from a global fit. This approach also allows us to study higher-twist corrections, which are a major source of systematic error. Our result for the higher-twist parameter delta(pi)(2) is in good agreement with estimates from QCD sum rules. Another novel element is the use of all-to-all propagators, calculated using stochastic estimators, which enables an additional volume average of the correlation functions, thereby reducing statistical errors
Nuclear Import and Export Signals of Human Cohesins SA1/STAG1 and SA2/STAG2 Expressed in Saccharomyces cerevisiae
Abstract
Background: Human SA/STAG proteins, homologues of the yeast Irr1/Scc3 cohesin, are the least studied constituents of the
sister chromatid cohesion complex crucial for proper chromosome segregation. The two SA paralogues, SA1 and SA2, show
some specificity towards the chromosome region they stabilize, and SA2, but not SA1, has been shown to participate in
transcriptional regulation as well. The molecular basis of this functional divergence is unknown.
Methodology/Principal Findings: In silico analysis indicates numerous putative nuclear localization (NLS) and export (NES)
signals in the SA proteins, suggesting the possibility of their nucleocytoplasmic shuttling. We studied the functionality of
those putative signals by expressing fluorescently tagged SA1 and SA2 in the yeast Saccharomyces cerevisiae. Only the Nterminal
NLS turned out to be functional in SA1. In contrast, the SA2 protein has at least two functional NLS and also two
functional NES. Depending on the balance between these opposing signals, SA2 resides in the nucleus or is distributed
throughout the cell. Validation of the above conclusions in HeLa cells confirmed that the same N-terminal NLS of SA1 is
functional in those cells. In contrast, in SA2 the principal NLS functioning in HeLa cells is different from that identified in
yeast and is localized to the C-terminus.
Conclusions/Significance: This is the first demonstration of the possibility of non-nuclear localization of an SA protein. The
reported difference in the organization between the two SA homologues may also be relevant to their partially divergent
functions. The mechanisms determining subcellular localization of cohesins are only partially conserved between yeast and
human cells
Immunogenicity and Safety of a Third COVID-19 BNT162b2 mRNA Vaccine Dose in 5- to 11-Year Olds
In this ongoing study, substantially increased ancestral SARSCoV-2 neutralizing responses were observed 1 month after a third 10-µg BNT162b2 dose given to 5 to 11-year olds versus neutralizing responses post-dose 2. After dose 3, increased neutralizing responses against Omicron BA.1 and BA.4/BA.5 strains were also observed. The safety/tolerability profile was acceptable.Peer reviewe
The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study
AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease
- …