The early precipitation process of Ni（75）Al（14）Mo（11） alloy was simulated by microscopic phase-field model at different temperatures.The microstructure of the alloy,the precipitation time of Llo structure and oc...The early precipitation process of Ni（75）Al（14）Mo（11） alloy was simulated by microscopic phase-field model at different temperatures.The microstructure of the alloy,the precipitation time of Llo structure and occupation probability of the three kinds of atoms were investigated.It is indicated that the non-stoichiometric Ll0（Ⅰ/Ⅱ） phases are found in the precipitation process.With the temperature increasing,the appearance time of Ll0 is brought forward.The Ll0（Ⅱ） structure always precipitates earlier than the Ll0（Ⅰ） structure.Compared with lower temperature,higher temperature brings the formation time of Ll0 phase forward and makes Ll0 phase have a higher order degree.But lower temperature shortens the process time of the Ll0 phase to the Ll2 phase.Al and Mo atoms tend to occupy γ site,Ni atom tends to occupy a and β sites.At the same temperature,Al atom has stronger occupation ability than Mo atom in the same site.Ni,Al and Mo collectively form the composited Ll2 structure.展开更多
This paper presents a new algorithm for optimization problems with nonlinear inequality constricts. At each iteration, the algorithm generates the search direction by solving only one quadratic programming (QP), and ...This paper presents a new algorithm for optimization problems with nonlinear inequality constricts. At each iteration, the algorithm generates the search direction by solving only one quadratic programming (QP), and then making a simple correction for the solution of the QP, moreover this new algorithm needn’t to do searching. The other advantage is that it may not only choose any point in En as a starting point, but also escape from the complex penalty function and diameter. moreover the iteration point will be a feasible descent sequence whenever some iteration point gets into the feasible region. So we call it subfeasible method.Under mild assumptions,the new algorithm is shown to possess global and two step superlinear convergence.展开更多
While ovarian cancer （OvCa） responds well to surgery and conventional chemotherapy, a high recurrence rate of advanced OvCa is observed. In this phase Ⅰ/Ⅱ study, 10 OvCa patients with minimal residual disease were...While ovarian cancer （OvCa） responds well to surgery and conventional chemotherapy, a high recurrence rate of advanced OvCa is observed. In this phase Ⅰ/Ⅱ study, 10 OvCa patients with minimal residual disease were treated with autologous dendritic cells （DCs） and IL-2 to evaluate the safety and feasibility of this therapeutic strategy and to characterize the antigen-specific immune alterations induced through this treatment. Approximately 4 months after initial debulking and chemotherapy, patients received two subcutaneous doses of autologous monocyte-derived DCs pulsed with autologous tumor lysate and keyhole limpet hemocyanin （KLH） at 4-week intervals. After each DC inoculation, low-dose （200 mlU） IL-2 was introduced for 14 consecutive days as an immune adjuvant. The vaccination was well tolerated. In three out of 10 patients, the inclusion status after the initial therapy showed the maintenance of complete remission （CR） after DC vaccination for 83, 80.9 and 38.2 months without disease relapse. One patient with stable disease （SD） experienced the complete disappearance of tumor after DC vaccination, and this status was maintained for 50.8 months until tumor recurrence. In two patients with partial response （PR） was not responding to DC vaccination and their disease recurred. In the three patients with disease free long-term survival, significant immune alterations were observed, including increased natural killer （NK） activity, IFN-γ-secreting T cells, immune-stimulatory cytokine secretion and reduced immune-suppressive factor secretion after DC vaccination. Thus, in patients with NED status and increased overall survival, DC vaccination induced tumor-related immunity, potentially associated with long-term clinical responses against OvCa.展开更多
We propose a new two-/three-stage dose-finding design called Target Toxicity(TT)for phase Ⅰ clinical trials,where we link the decision rules in the dose-finding process with the conclusions from a hypothesis test.The...We propose a new two-/three-stage dose-finding design called Target Toxicity(TT)for phase Ⅰ clinical trials,where we link the decision rules in the dose-finding process with the conclusions from a hypothesis test.The power to detect excessive toxicity is also given.This solves the problem of why the minimal number of patients is needed for the selected dose level.Our method provides a statistical explanation of traditional‘3+3’design using frequentist framework.The proposed method is very flexible and it incorporates other interval-based decision rules through different parameter settings.We provide the decision tables to guide investigators when to decrease,increase or repeat a dose for next cohort of subjects.Simulation experiments were conducted to compare the performance of the proposed method with other dose-finding designs.A free open source R package tsdf is available on CRAN.It is dedicated to deriving two-/three-stage design decision tables and perform dose-finding simulations.展开更多
基金Project(51275486)supported by the National Natural Science Foundation of China
文摘The early precipitation process of Ni（75）Al（14）Mo（11） alloy was simulated by microscopic phase-field model at different temperatures.The microstructure of the alloy,the precipitation time of Llo structure and occupation probability of the three kinds of atoms were investigated.It is indicated that the non-stoichiometric Ll0（Ⅰ/Ⅱ） phases are found in the precipitation process.With the temperature increasing,the appearance time of Ll0 is brought forward.The Ll0（Ⅱ） structure always precipitates earlier than the Ll0（Ⅰ） structure.Compared with lower temperature,higher temperature brings the formation time of Ll0 phase forward and makes Ll0 phase have a higher order degree.But lower temperature shortens the process time of the Ll0 phase to the Ll2 phase.Al and Mo atoms tend to occupy γ site,Ni atom tends to occupy a and β sites.At the same temperature,Al atom has stronger occupation ability than Mo atom in the same site.Ni,Al and Mo collectively form the composited Ll2 structure.
文摘This paper presents a new algorithm for optimization problems with nonlinear inequality constricts. At each iteration, the algorithm generates the search direction by solving only one quadratic programming (QP), and then making a simple correction for the solution of the QP, moreover this new algorithm needn’t to do searching. The other advantage is that it may not only choose any point in En as a starting point, but also escape from the complex penalty function and diameter. moreover the iteration point will be a feasible descent sequence whenever some iteration point gets into the feasible region. So we call it subfeasible method.Under mild assumptions,the new algorithm is shown to possess global and two step superlinear convergence.
文摘While ovarian cancer （OvCa） responds well to surgery and conventional chemotherapy, a high recurrence rate of advanced OvCa is observed. In this phase Ⅰ/Ⅱ study, 10 OvCa patients with minimal residual disease were treated with autologous dendritic cells （DCs） and IL-2 to evaluate the safety and feasibility of this therapeutic strategy and to characterize the antigen-specific immune alterations induced through this treatment. Approximately 4 months after initial debulking and chemotherapy, patients received two subcutaneous doses of autologous monocyte-derived DCs pulsed with autologous tumor lysate and keyhole limpet hemocyanin （KLH） at 4-week intervals. After each DC inoculation, low-dose （200 mlU） IL-2 was introduced for 14 consecutive days as an immune adjuvant. The vaccination was well tolerated. In three out of 10 patients, the inclusion status after the initial therapy showed the maintenance of complete remission （CR） after DC vaccination for 83, 80.9 and 38.2 months without disease relapse. One patient with stable disease （SD） experienced the complete disappearance of tumor after DC vaccination, and this status was maintained for 50.8 months until tumor recurrence. In two patients with partial response （PR） was not responding to DC vaccination and their disease recurred. In the three patients with disease free long-term survival, significant immune alterations were observed, including increased natural killer （NK） activity, IFN-γ-secreting T cells, immune-stimulatory cytokine secretion and reduced immune-suppressive factor secretion after DC vaccination. Thus, in patients with NED status and increased overall survival, DC vaccination induced tumor-related immunity, potentially associated with long-term clinical responses against OvCa.
文摘We propose a new two-/three-stage dose-finding design called Target Toxicity(TT)for phase Ⅰ clinical trials,where we link the decision rules in the dose-finding process with the conclusions from a hypothesis test.The power to detect excessive toxicity is also given.This solves the problem of why the minimal number of patients is needed for the selected dose level.Our method provides a statistical explanation of traditional‘3+3’design using frequentist framework.The proposed method is very flexible and it incorporates other interval-based decision rules through different parameter settings.We provide the decision tables to guide investigators when to decrease,increase or repeat a dose for next cohort of subjects.Simulation experiments were conducted to compare the performance of the proposed method with other dose-finding designs.A free open source R package tsdf is available on CRAN.It is dedicated to deriving two-/three-stage design decision tables and perform dose-finding simulations.
