Glueball mass from quantized knot solitons and gauge-invariant gluon mass

We propose an approach which enables one to obtain simultaneously the glueball mass and the gluon mass in the gauge-invariant way to shed new light on the mass gap problem in Yang-Mills theory. First, we point out that the Faddeev (Skyrme--Faddeev-Niemi) model can be induced through the gauge-invariant vacuum condensate of mass dimension two from SU(2) Yang-Mills theory. Second, we obtain the glueball mass spectrum by performing the collective coordinate quantization of the topological knot soliton in the Faddeev model. Third, we demonstrate that a relationship between the glueball mass and the gluon mass is obtained, since the gauge-invariant gluon mass is also induced from the relevant vacuum condensate. Finally, we determine physical values of two parameters in the Faddeev model and give an estimate of the relevant vacuum condensation in Yang-Mills theory. Our results indicate that the Faddeev model can play the role of a low-energy effective theory of the quantum SU(2) Yang-Mills theory.Comment: 17 pages, 2 figures, 3 tables; a version accepted for publication in J. Phys. A: Math. Gen.; Sect. 2 and sect. 5 (old sect. 4) are modified. Sect. 4, Tables 1 and Table 3 are adde

Dynamic Meso-Scale Anchorage of GPI-Anchored Receptors in the Plasma Membrane: Prion Protein vs. Thy1

The central mechanism for the transmission of the prion protein misfolding is the structural conversion of the normal cellular prion protein to the pathogenic misfolded prion protein, by the interaction with misfolded prion protein. This process might be enhanced due to the homo-dimerization/oligomerization of normal prion protein. However, the behaviors of normal prion protein in the plasma membrane have remained largely unknown. Here, using single fluorescent-molecule imaging, we found that both prion protein and Thy1, a control glycosylphosphatidylinositol-anchored protein, exhibited very similar intermittent transient immobilizations lasting for a few seconds within an area of 24.2 and 3.5 nm in diameter in CHO-K1 and hippocampal neurons cultured for 1- and 2-weeks, respectively. Prion protein molecules were immobile during 72% of the time, approximately 1.4× more than Thy1, due to prion protein’s higher immobilization frequency. When mobile, prion protein diffused 1.7× slower than Thy1. Prion protein’s slower diffusion might be caused by its transient interaction with other prion protein molecules, whereas its brief immobilization might be due to temporary association with prion protein clusters. Prion protein molecules might be newly recruited to prion protein clusters all the time, and simultaneously, prion protein molecules in the cluster might be departing continuously. Such dynamic interactions of normal prion protein molecules would strongly enhance the spreading of misfolded prion protein

The Pion Decay Constants and the Rho-Meson Mass at Finite Temperature in the Hidden Local Symmetry

We study the temperature dependence of the pion decay constant and rho-meson mass in the hidden local symmetry model at one loop. Using the standard imaginary time formalism, we include the thermal effect of rho meson as well as that of pion. We show that the pion gives a dominant contribution to the pion decay constant and rho-meson contribution slightly decreases the critical temperature. The rho-meson pole mass increases as T^4/m_\rho^2 at low temperature dominated by the pion-loop effect. At high temperature, although the pion-loop effect decreases the rho-meson mass, the rho-loop contribution overcomes the pion-loop contribution and rho-meson mass increases with temperature. We also show that the conventional parameter a is stable as the temperature increases.Comment: We added a comment on the correction to the rho-meson mass from the omega-pi loop. This is the final version to be published in Phys. Rev. D. 19 pages (LaTeX-RevTeX), 7 PostScript figure

Chiral Phase Transition of QCD at Finite Temperature and Density from Schwinger-Dyson Equation

We study the chiral phase transition of QCD at finite temperature and density by numerically solving Schwinger-Dyson equation for the quark propagator with the improved ladder approximation in the Landau gauge. Using the solution we calculate a pion decay constant from a generalized version of Pagels-Stokar formula. Chiral phase transition point is determined by analyzing an effective potential for the quark propagator. We find solutions for which chiral symmetry is broken while the value of the effective potential is larger than that for the chiral symmetric vacuum. These solutions correspond to meta-stable states, and the chiral symmetric vacuum is energetically favored. We present a phase diagram on the general temperature--chemical potential plane, and show that phase transitions are of first order in wide range.Comment: 23 pages (LaTeX-RevTeX), 14 PostScript figure

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Development of a molecularly evolved, highly sensitive CaMKII FRET sensor with improved expression pattern.

Genetically encoded fluorescence resonance energy transfer (FRET) biosensors have been successfully used to visualize protein activity in living cells. The sensitivity and accuracy of FRET measurements directly depend on biosensor folding efficiency, expression pattern, sensitivity, and dynamic range. Here, to improve the folding efficiency of the Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIα) FRET biosensor, we amplified the association domain of the CaMKIIα gene using error-prone polymerase chain reaction (PCR) and fused it to the N-terminus of mCherry in a bacterial expression vector. We also created an Escherichia coli expression library based on a previously reported fluorescent protein folding reporter method, and found a bright red fluorescent colony that contained the association domain with four mutations (F394L, I419V, A430T, and I434T). In vitro assays using the purified mutant protein confirmed improved folding kinetics of the downstream fluorescent protein, but not of the association domain itself. Furthermore, we introduced these mutations into the previously reported CaMKIIα FRET sensor and monitored its Ca2+/calmodulin-dependent activation in HeLa cells using 2-photon fluorescence lifetime imaging microscopy (2pFLIM), and found that the expression pattern and signal reproducibility of the mutant sensor were greatly improved without affecting the autophosphorylation function and incorporation into oligomeric CaMKIIα. We believe that our improved CaMKIIα FRET sensor would be useful in various types of cells and tissues, providing data with high accuracy and reproducibility. In addition, the method described here may also be applicable for improving the performance of all currently available FRET sensors

Schematic diagram of CaMKIIα FRET sensor evolution.

<p><b>(A)</b> The CaMKIIα fluorescence resonance energy transfer (FRET) sensor (Camuiα) consists of FRET donor (mEGFP) and acceptor fluorophores (sREACh) and full-length CaMKIIα, which contains kinase, regulatory, and association domains. For improving the folding efficiency of the sensor, the association domain was amplified by error-prone PCR and subcloned into a bacterial expression vector. Subsequently, the ligated DNA was transformed in <i>Escherichia coli</i> to make a library. Bright red colonies were isolated from the library and analyzed by DNA sequencing. The identified mutations were then incorporated into the FRET sensor, leading to an increase in its folding efficiency. This scheme is based on an assumption that the folding efficiency of the association domain is coupled to that of mCherry. <b>(B)</b> The crystal structure of the association domain of human CaMKIIβ7 (PDB code: 3SOA). Note that this sequence is identical to the corresponding region in rat CaMKIIα (345–474) used in this study. The positions of four mutations (F394L, I419V, A430T, and I434T) found in this study are shown in red.</p

Camuiα4m-mGsR activation by single-spine stimulation.

<p><b>(A)</b> Fluorescence lifetime images of neurons expressing Camuiα4m-mGsR together with tandem mCherry during the induction of spine enlargement by 2-photon glutamate uncaging. The arrowhead indicates the stimulated spine. <b>(B)</b> Time courses of Camuiα mutants activities measured as a change in the fluorescence lifetime of Camuiα-mGsR, Camuiα4m-mGsR, Camuiα4m (T286A)-mGsR in the stimulated spines are overlaid with the spine volume change measured as a change in the mCherry fluorescence, respectively. The numbers of samples (spines/neurons) are 6/4 for wild-type, 9/5 for 4m, and 10/6 for 4m with T286A, respectively. Error bars are S.E.M. in <b>B</b>-<b>E</b>. <b>(C)</b> Peak Camuiα mutants activation (averaged over 0–24 s). Stars denote statistical significance (p < 0.05, ANOVA followed by the least significant difference (LSD) test). (<b>D)</b> Averaged time courses of spine volume change in the same experiments in <b>B</b>. (<b>E)</b> Transient (volume change averaged over 2–4 min subtracted by that over 15–18 min) and sustained volume change (volume change averaged over 15–18 min). Stars denote statistical significance (p < 0.05, ANOVA followed by the LSD tests).</p