PI3K (phosphoinositide 3-kinase)/AKT and RAS/MAPK (mitogen-activated protein kinase) pathway coactivation in the prostate epithelium promotes both epithelial-mesenchymal transition (EMT) and ...metastatic castration-resistant prostate cancer (mCRPC), which is currently incurable. To study the dynamic regulation of the EMT process, we developed novel genetically defined cellular and in vivo model systems from which epithelial, EMT and mesenchymal-like tumor cells with Pten deletion and Kras activation can be isolated. When cultured individually, each population has the capacity to regenerate all three tumor cell populations, indicative of epithelial-mesenchymal plasticity. Despite harboring the same genetic alterations, mesenchymal-like tumor cells are resistant to PI3K and MAPK pathway inhibitors, suggesting that epigenetic mechanisms may regulate the EMT process, as well as dictate the heterogeneous responses of cancer cells to therapy. Among differentially expressed epigenetic regulators, the chromatin remodeling protein HMGA2 is significantly upregulated in EMT and mesenchymal-like tumors cells, as well as in human mCRPC. Knockdown of HMGA2, or suppressing HMGA2 expression with the histone deacetylase inhibitor LBH589, inhibits epithelial-mesenchymal plasticity and stemness activities in vitro and markedly reduces tumor growth and metastasis in vivo through successful targeting of EMT and mesenchymal-like tumor cells. Importantly, LBH589 treatment in combination with castration prevents mCRPC development and significantly prolongs survival following castration by enhancing p53 and androgen receptor acetylation and in turn sensitizing castration-resistant mesenchymal-like tumor cells to androgen deprivation therapy. Taken together, these findings demonstrate that cellular plasticity is regulated epigenetically, and that mesenchymal-like tumor cell populations in mCRPC that are resistant to conventional and targeted therapies can be effectively treated with the epigenetic inhibitor LBH589.
We experimentally realize a universal set of single-bit and two-bit geometric quantum gates by adiabatically controlling solid-state spins in a diamond defect. Compared with the nonadiabatic ...approach, the adiabatic scheme for geometric quantum computation offers a unique advantage of inherent robustness to parameter variations, which is explicitly demonstrated in our experiment by showing that the single-bit gates remain unchanged when the driving field amplitude varies by a factor of 2 or the detuning fluctuates in a range comparable to the inverse of the gate time. The reported adiabatic control technique and its convenient implementation offer a paradigm for achieving quantum computation through robust geometric quantum gates, which is important for quantum information systems with parameter-fluctuation noise such as those from the inhomogeneous coupling or the spectral diffusion.
We present an improved analysis of the final data set from the QUaD experiment. Using an improved technique to remove ground contamination, we double the effective sky area and hence increase the ...precision of our cosmic microwave background (CMB) power spectrum measurements by ~30% versus that previously reported. In addition, we have improved our modeling of the instrument beams and have reduced our absolute calibration uncertainty from 5% to 3.5% in temperature. The robustness of our results is confirmed through extensive jackknife tests, and by way of the agreement that we find between our two fully independent analysis pipelines. For the standard six-parameter Delta *LCDM model, the addition of QUaD data marginally improves the constraints on a number of cosmological parameters over those obtained from the WMAP experiment alone. The impact of QUaD data is significantly greater for a model extended to include either a running in the scalar spectral index, or a possible tensor component, or both. Adding both the QUaD data and the results from the Arcminute Cosmology Bolometer Array Receiver experiment, the uncertainty in the spectral index running is reduced by ~25% compared to WMAP alone, while the upper limit on the tensor-to-scalar ratio is reduced from r < 0.48 to r < 0.33 (95% c.l.). This is the strongest limit on tensors to date from the CMB alone. We also use our polarization measurements to place constraints on parity-violating interactions to the surface of last scattering, constraining the energy scale of Lorentz violating interactions to <1.5 X 10-43 GeV (68% c.l.). Finally, we place a robust upper limit on the strength of the lensing B-mode signal. Assuming a single flat band power between = 200 and = 2000, we constrain the amplitude of B-modes to be <0.57 Delta *mK2 (95% c.l.).
Quantum simulation of 1D relativistic quantum mechanics has been achieved in well-controlled systems like trapped ions, but properties like spin dynamics and response to external magnetic fields that ...appear only in higher dimensions remain unexplored. Here we simulate the dynamics of a 2D Weyl particle. We show the linear dispersion relation of the free particle and the discrete Landau levels in a magnetic field, and we explicitly measure the spatial and spin dynamics from which the conservation of helicity and properties of antiparticles can be verified. Our work extends the application of an ion trap quantum simulator in particle physics with the additional spatial and spin degrees of freedom.
To assess the predictive value of major adverse cardiac events (MACEs) in patients with acute myocardial infarction (AMI) by T2-mapping texture analysis (TA) of the myocardial remote zone.
Data from ...155 patients, who were diagnosed with AMI and were treated with primary percutaneous coronary intervention (PPCI), and 32 healthy controls who underwent cardiac magnetic resonance imaging (CMRI) were analysed retrospectively. T2-mapping TA of the myocardial remote zone was conducted accordingly. The patients were divided into two subgroups according to the occurrence of MACEs. The primary outcome was a composite of MACEs.
Among 155 patients, 32 (20.6%) patients suffered MACEs, and the most common event was non-sustained ventricular tachycardia (84.3%). Five independent texture features on T2-mapping were selected: Perc.50%, S(4,-4)AngScMom, S(1,1)InvDfMom, S(0,2)DifEntrp, and Horzl_LngREmph. Among them, the mean value of Horzl_LngREmph in the myocardial remote zone among all patients, MACEsnegative, and MACEs-positive was 21.64, 19.12, and 34.52, respectively. Horzl_LngREmph provided the highest area under the receiver operating characteristic (ROC) curve (AUC) value, which enabled two subgroups to be distinguished (AUC = 0.914, p<0.05). According to the results of the univariate analysis, combined with late gadolinium enhancement (LGE) extent and the presence of left ventricular hypertrophy, Horzl_LngREmph, was strongly associated with the occurrence of MACEs (p<0.05, hazard ratio: 1.64, 95% confidence interval: 1.10–4.51).
Together with LGE extent, Horzl_LngREmph, a texture feature obtained from T2-mapping TA of the myocardial remote zone, could predict the occurrence of MACEs in AMI patients.
•TA of the remote zone of T2-Mapping can predict the occurrence of MACEs in AMI.•Horzl_LngREmph has good consistency with LGE in the predication of AMI prognosis.•20% MI patients suffered from MACEs, and non-sustained VT was the most popular.
Objective
To examine the associations between personality traits and suicidal ideation (SI) and attempt (SA) in mood disorder patients and community controls.
Method
We recruited 365 bipolar, 296 ...major depressive disorder patients, and 315 community controls to assess their lifetime suicidality. Participants filled out self‐reported personality questionnaires to collect data of personality traits, including novelty seeking (NS), harm avoidance (HA), extraversion (E), and neuroticism (N). We used logistic regression models adjusted for diagnoses to analyze combinational effects of personality traits on the risk of suicide. Additionally, radar charts display personality profiles for suicidal behaviours by groups.
Results
All personality traits were associated with the risk of suicidality with various effect size, except for E that showed protective effect. High N or HA had prominent and independent risk effects on SI and SA. Combinations of high N and low E, or high HA and NS were the risk personality profiles for suicidality. Higher N scores further distinguished SA from SI in mood disorder patients.
Conclusion
Introvert personality traits showed independent risk effects on suicidality regardless of diagnosis status. Among high‐risk individuals with suicidal thoughts, higher neuroticism tendency is further associated with increased risk of suicide attempt.
To assess the potential of texture analysis (TA) applied in T1 maps and extracellular volume (ECV) obtained using cardiac magnetic resonance (CMR) in the diagnosis of hypertrophic cardiomyopathy ...(HCM) and hypertensive heart disease (HHD) compared with normal controls (NC). Strain parameters were analysed to compare with final TA models.
This retrospective study included 66 HCM patients, 39 HHD patients, and 41 NC. Step-wise dimension reduction and feature selection were performed by reproducibility, machine learning, collinearity, and multivariable regression analysis to select the texture features that enable diagnosis of and differentiation between HCM and HHD. Strain parameters were calculated by short-axis and three long-axis cine sequences.
Independent features in T1 maps and ECV analysis allowed for the differentiation between patients (HCM and HHD) and NC. Of the best-calculated model, the areas under the receiver operating curve (AUCs) were as follows: 0.969 for T1 map and 0.964 for ECV. To distinguish HCM from HHD, two independent features were screened out for both T1 and ECV maps. The AUCs were as follows: 0.793 for T1 map and 0.894 for ECV. Radial, circumferential, and longitudinal strain parameters could differentiate patients from NC, but only longitudinal strain parameters was significantly different between HCM and HHD.
Texture analysis of T1 maps and ECV shows high accuracy in differentiating hypertrophic myocardium from NC, and HCM from HHD. Strain parameters are able to demonstrate the difference between patients and NC, but were less impressive in differentiating HCM and HHD.
•Texture analyses of native T1 map could differentiate patients from normal controls.•Texture analyses of native T1 map could also discriminate between HCM and HHD.•The diagnosis accuracies were comparable with strain parameters.
There is strong circumstantial evidence that certain heavy, unstable atomic nuclei are 'octupole deformed', that is, distorted into a pear shape. This contrasts with the more prevalent rugby-ball ...shape of nuclei with reflection-symmetric, quadrupole deformations. The elusive octupole deformed nuclei are of importance for nuclear structure theory, and also in searches for physics beyond the standard model; any measurable electric-dipole moment (a signature of the latter) is expected to be amplified in such nuclei. Here we determine electric octupole transition strengths (a direct measure of octupole correlations) for short-lived isotopes of radon and radium. Coulomb excitation experiments were performed using accelerated beams of heavy, radioactive ions. Our data on (220)Rn and (224)Ra show clear evidence for stronger octupole deformation in the latter. The results enable discrimination between differing theoretical approaches to octupole correlations, and help to constrain suitable candidates for experimental studies of atomic electric-dipole moments that might reveal extensions to the standard model.
Follicular lymphoma (FL) is typically an indolent disease, but 30-40% of FL cases transform into an aggressive lymphoma (tFL) with a poor prognosis. To identify the genetic changes that drive this ...transformation, we sequenced the exomes of 12 cases with paired FL and tFL biopsies and identified 45 recurrently mutated genes in the FL-tFL data set and 39 in the tFL cases. We selected 496 genes of potential importance in transformation and sequenced them in 23 additional tFL cases. Integration of the mutation data with copy-number abnormality (CNA) data provided complementary information. We found recurrent mutations of miR-142, which has not been previously been reported to be mutated in FL/tFL. The genes most frequently mutated in tFL included KMT2D (MLL2), CREBBP, EZH2, BCL2 and MEF2B. Many recurrently mutated genes are involved in epigenetic regulation, the Janus-activated kinase-signal transducer and activator of transcription (STAT) or the nuclear factor-κB pathways, immune surveillance and cell cycle regulation or are TFs involved in B-cell development. Of particular interest are mutations and CNAs affecting S1P-activated pathways through S1PR1 or S1PR2, which likely regulate lymphoma cell migration and survival outside of follicles. Our custom gene enrichment panel provides high depth of coverage for the study of clonal evolution or divergence.
To measure the left atrial (LA) function in patients with hypertrophic cardiomyopathy (HCM; with OHCM and without obstruction NOHCM) and hypertension-related left ventricular hypertrophy (H-LVH) ...using cardiovascular magnetic resonance imaging feature tracking (CMR-FT).
Patients who met the criteria for HCM (n=68), H-LVH (n=46), and 30 healthy controls participated. Left atrial strain was analysed using CMR-FT in cine images with two and four chambers.
The strain rate and LA strain measurements showed that patients with HCM, and H-LVH had impaired conduit and reservoir functions (versus controls). These capacities were more severely impaired in OHCM than those seen in NOHCM and H-LVH. The LA volume parameters (LAVIpac, LAVImin and LAVImax) from the OHCM group were higher than both the NOHCM and H-LVH groups (all p<0.05). There were differences between the OHCM and H-LVH groups in terms of the parameters for LA reservoir function (εs), booster pump function (SRa), and conduit function (SRe, LA passive EF, εe; p<0.05). The strongest correlations included the associations between LA total EF and εs, εe and LA passive EF, and SRe and LA passive EF.
CMR-FT can reliably identify LA dysfunction and deformation in the early stages of HCM and H-LVH.
•CMR-FT can be employed to evaluate left atrial dysfunction and deformation•Early differential diagnosis of hypertension and hypertrophic cardiomyopathy•Myocardial strain is a sensitive indicator of early impairment of cardiac function•The left atrial strain parameter may be able to identify lesions earlier
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