Somatic cells can be reprogrammed into pluripotent stem cells (PSCs) by using pure chemicals, providing a different paradigm to study somatic reprogramming. However, the cell fate dynamics and molecular events that occur during the chemical reprogramming process remain unclear. We now show that the chemical reprogramming process requires the early formation of extra-embryonic endoderm (XEN)-like cells and a late transition from XEN-like cells to chemically-induced (Ci)PSCs, a unique route that fundamentally differs from the pathway of transcription factor-induced reprogramming. Moreover, precise manipulation of the cell fate transition in a step-wise manner through the XEN-like state allows us to identify small-molecule boosters and establish a robust chemical reprogramming system with a yield up to 1,000-fold greater than that of the previously reported protocol. These findings demonstrate that chemical reprogramming is a promising approach to manipulate cell fates.
We consider the problem of small data global existence for a class of semilinear wave equations with null condition on a Lorentzian background (R 3+1 , g) with a time dependent metric g coinciding with Minkowski metric outside the cylinder { (t, x)| |x| ≤ R}. We show that the small data global existence result can be reduced to two integrated local energy estimates and demonstrate these estimates in the particular case when g is merely C 1 close to the Minkowski metric. One of the novel aspects of this work is that it applies to equations on backgrounds which do not settle to any particular stationary metric.
OBJECTIVE:To predict the American Joint Cancer Committee tumor-node-metastasis stage in patients with papillary thyroid carcinoma by evaluating the relationship between the preoperative neutrophil-to-lymphocyte ratio and the tumor-node-metastasis stage.METHODS:We retrospectively examined 161 patients with a diagnosis of papillary thyroid carcinoma. The Neutrophil-to-Lymphocyte Ratio was calculated according to the absolute neutrophil counts and absolute lymphocyte counts on routine blood tests obtained prior to surgery and patients with a Neutrophil-to-Lymphocyte Ratio of 2.0 or more were classified as the high NLR group, while those with a Neutrophil-to-Lymphocyte Ratio less than 2.0 were classified as the low Neutrophil-to-Lymphocyte Ratio group. Clinicopathological variables, which were stratified by the Neutrophil-to-Lymphocyte Ratio, were analyzed. A multivariate analysis was performed to determine factors that affect the Neutrophil-to-Lymphocyte Ratio. The association between the Neutrophil-to-Lymphocyte Ratio and the TNM stage in patients ≥45 years of age was analyzed using the Spearman rank correlation.RESULTS:Various blood indices, including hemoglobin, platelet and thyroid-stimulating hormone levels in the two groups showed no significant differences. Lymph node metastasis, multifocality and tumor size exhibited significant differences in the two groups (p=0.000, p=0.000 and p=0.035, respectively). Correlation analysis indicated that a higher preoperative Neutrophil-to-Lymphocyte Ratio was observed in patients with lymph node metastasis, larger tumor size and multifocality (r=0.341, p=0.000; r=0.271, p=0.000; and r=0.182, p=0.010, respectively). For patients ≥45 years of age, the number of patients with an advanced TNM stage in the high NLR group was higher than that in the low Neutrophil-to-Lymphocyte Ratio group (p=0.013). A linear regression analysis showed that the preoperative Neutrophil-to-Lymphocyte Ratio was positively correlated with the American Joint Cancer Committee tumor-node-metastasis stage (rho=0.403, p=0.000).CONCLUSION:The preoperative Neutrophil-to-Lymphocyte Ratio was closely related to the stage of papillary thyroid carcinoma. The increase in the preoperative Neutrophil-to-Lymphocyte Ratio contributed to the advanced tumor-node-metastasis stage of papillary thyroid carcinoma patients ≥45 years of age.
It is well-known that in dimensions at least three semilinear wave equations with null conditions admit global solutions for small initial data. It is also known that in dimension two such result still holds for a certain class of quasi-linear wave equations with null conditions. The proofs are based on the decay mechanism of linear waves. However, in one dimension, waves do not decay. Nevertheless, we will prove that small data still lead to global solutions if the null condition is satisfied.
We consider the problem of small data global existence for quasilinear wave equations with null condition on a class of Lorentzian manifolds (R 3+1 , g) with time dependent inhomogeneous metric. We show that sufficiently small data give rise to a unique global solution for metric which is merely C 1 close to the Minkowski metric inside some large cylinder { (t, x)| |x| ≤ R} and approaches the Minkowski metric weakly as |x| → ∞. Based on this result, we give weak but sufficient conditions on a given large solution of quasilinear wave equations such that the solution is globally stable under perturbations of initial data. * This work is part of the author's Ph.D. thesis at Princeton University. Preliminaries and Energy MethodGiven any Lorentzian metric g = g µν dx µ dx ν , x 0 = t on R 3+1 , we let g µν denotes the components of the inverse of the metric g. Throughout this paper, we let A, B be any vector fields in {L, L, S 1 , S 2 } and S be any vector fields in {S 1 , S 2 }. Relative to the null frame, the metric components are g AB . The inverse is g AB . We denote ∂ µ = g µν ∂ ν , ∂ A = g AB B.
On the three dimensional Euclidean space, for data with finite energy, it is well-known that the Maxwell-Klein-Gordon equations admit global solutions. However, the asymptotic behaviours of the solutions for the data with non-vanishing charge and arbitrary large size are unknown. It is conjectured that the solutions disperse as linear waves and enjoy the so-called peeling properties for pointwise estimates. We provide a gauge independent proof of the conjecture.
In this paper, we study the asymptotic pointwise decay properties for solutions of energy subcritical defocusing semilinear wave equations in R 3+1 . We prove that the solution decays as quickly as linear waves for p > 1+ √ 17 2, covering part of the subconformal case, while for the range 2 < p ≤ 1+ √ 17 2 , the solution still decays with rate at least t − 1 3 . As a consequence, the solution scatters in energy space when p > 2.3542.. As a consequence, the solution scatters in energy space for p > 2.7005.The aim of this paper are two folds: firstly we obtain pointwise decay estimate for the solution with data in some weighted energy space which is weaker than the conformal energy space required in previous works. We prove that the solution decays as quickly as linear waves (with the same initial data) for all p > 1+ √ 17 2, covering additional part of the subconformal range. Secondly for even smaller p with lower bound 2, we show that the solution decays at least t − 1 3 . This decay estimate immediately leads to the
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