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The chemoresistance of temozolomide-based therapy is a serious limitation for lasting effective treatment of gliomas, while the underlying mechanisms remain unclear. In this study, we showed that downregulation of BASP1 correlated negatively with the response to temozolomide therapy and disease-free survival (DFS) of patients with gliomas. Silencing BASP1 significantly enhanced the temozolomide resistance of glioma cells both in vitro and in vivo through repair of temozolomide-induced DNA damage via activation of the FBXO32/NF-κB/MGMT axis in both MGMT-methylated and -unmethylated gliomas. We demonstrated that loss of BASP1 resulted in removal of TRIM37/EZH2 complex–induced repressive histone modifications, including H2A-ub and H3K27me3, but addition of WDR5/MLL complex–mediated active histone modifications, including H3K4me3 and H3K9ac, on the FBXO32 promoter, which elicited in FBXO32 upregulation and further activated NF-κB/MGMT signaling via ubiquitin-dependent degradation of IκBα. Importantly, treatment with OICR-9429, an antagonist of the WDR5–MLL interaction, impaired the FBXO32/NF-κB/MGMT axis–mediated repair of temozolomide-induced DNA damage, leading to significant apoptosis of BASP1-downregulated glioma cells. These findings shed light on the molecular mechanism underlying BASP1-mediated epigenetic transcriptional repression and may represent a potential strategy in the fight against temozolomide-resistant gliomas. Implications: BASP1 downregulation promotes temozolomide resistance in gliomas through WDR5/MLL complex–mediated epigenetic activation of the FBXO32/NF-κB/MGMT axis, providing new target for improving outcomes in patients with temozolomide-resistant gliomas.

Sustaining DNA damage response (DDR) signalling via retention of DDR factors at damaged sites is important for transmitting damage-sensing and repair signals. Herein, we found that DNA damage provoked the association of ribosomes with IRES region in lncRNA CTBP1-DT, which overcame the negative effect of upstream open reading frames (uORFs), and elicited the novel microprotein DNA damage-upregulated protein (DDUP) translation via a cap-independent translation mechanism. Activated ATR kinase-mediated phosphorylation of DDUP induced a drastic ‘dense-to-loose’ conformational change, which sustained the RAD18/RAD51C and RAD18/PCNA complex at damaged sites and initiated RAD51C-mediated homologous recombination and PCNA-mediated post-replication repair mechanisms. Importantly, treatment with ATR inhibitor abolished the effect of DDUP on chromatin retention of RAD51C and PCNA, thereby leading to hypersensitivity of cancer cells to DNA-damaging chemotherapeutics. Taken together, our results uncover a plausible mechanism underlying the DDR sustaining and might represent an attractive therapeutic strategy in improvement of DNA damage-based anticancer therapies.

S1. BASP1 downregulation is associated with poor prognosis in glioma patients.S2. Low expression of BASP1 is associated with poor prognosis in CGGA dataset.S3. Dysregulation of BASP1 alters chemoresistance of glioma cells to TMZ treatment in vitro.S4. BASP1 dysregulation has no effect on the rate of glioma cell growth in vivo.S5. Dysregulation of BASP1 alters chemoresistance to TMZ treatment in glioma cells in vivo.S6. BASP1 silencing activates NF-κB signaling in glioma cells.S7. FBXO32 expression correlates with NF-κB signaling.S8. BXO32 expression positively correlates with MGMT expression.S9. FBXO32 is associated with poor prognosis of glioma patients.S10. WDR5/MLL upregulates FBXO32 epigenetically.S11. Combined OICR-9429 sensitizes BASP1-silenced glioma cells to TMZ in vivo.Supplementary Table S1. Clinicopathological characteristics of studied patients and BASP1 expression in gliomas.Supplementary Table S2. Correlation between the clinicopathological features and expression.Supplementary Table S3. Univariate and multivariate analysis of different prognostic parameters in glioma patients by Cox-regression analysis.Supplementary Table S4. Primers and Oligonucleotides used in this study.

The chemoresistance of temozolomide-based therapy is a serious limitation for lasting effective treatment of gliomas, while the underlying mechanisms remain unclear. In this study, we showed that downregulation of BASP1 correlated negatively with the response to temozolomide therapy and disease-free survival (DFS) of patients with gliomas. Silencing BASP1 significantly enhanced the temozolomide resistance of glioma cells both in vitro and in vivo through repair of temozolomide-induced DNA damage via activation of the FBXO32/NF-κB/MGMT axis in both MGMT-methylated and -unmethylated gliomas. We demonstrated that loss of BASP1 resulted in removal of TRIM37/EZH2 complex–induced repressive histone modifications, including H2A-ub and H3K27me3, but addition of WDR5/MLL complex–mediated active histone modifications, including H3K4me3 and H3K9ac, on the FBXO32 promoter, which elicited in FBXO32 upregulation and further activated NF-κB/MGMT signaling via ubiquitin-dependent degradation of IκBα. Importantly, treatment with OICR-9429, an antagonist of the WDR5–MLL interaction, impaired the FBXO32/NF-κB/MGMT axis–mediated repair of temozolomide-induced DNA damage, leading to significant apoptosis of BASP1-downregulated glioma cells. These findings shed light on the molecular mechanism underlying BASP1-mediated epigenetic transcriptional repression and may represent a potential strategy in the fight against temozolomide-resistant gliomas.Implications:BASP1 downregulation promotes temozolomide resistance in gliomas through WDR5/MLL complex–mediated epigenetic activation of the FBXO32/NF-κB/MGMT axis, providing new target for improving outcomes in patients with temozolomide-resistant gliomas.

Mitochondrial dynamics play vital roles in the tumorigenicity and malignancy of various types of cancers by promoting the tumor-initiating potential of cancer cells, suggesting that targeting crucial factors that drive mitochondrial dynamics may lead to promising anticancer therapies. In the current study, we report that overexpression of mitochondrial fission factor (MFF), which is upregulated significantly in liver cancer–initiating cells (LCIC), promotes mitochondrial fission and enhances stemness and tumor-initiating capability in non-LCICs. MFF-induced mitochondrial fission evoked mitophagy and asymmetric stem cell division and promoted a metabolic shift from oxidative phosphorylation to glycolysis that decreased mitochondrial reactive oxygen species (ROS) production, which prevented ROS-mediated degradation of the pluripotency transcription factor OCT4. CRISPR affinity purification in situ of regulatory elements showed that T-box transcription factor 19 (TBX19), which is overexpressed uniquely in LCICs compared with non-LCICs and liver progenitor cells, forms a complex with PRMT1 on the MFF promoter in LCICs, eliciting epigenetic histone H4R3me2a/H3K9ac-mediated transactivation of MFF. Targeting PRMT1 using furamidine, a selective pharmacologic inhibitor, suppressed TBX19-induced mitochondrial fission, leading to a profound loss of self-renewal potential and tumor-initiating capacity of LCICs. These findings unveil a novel mechanism underlying mitochondrial fission–mediated cancer stemness and suggest that regulation of mitochondrial fission via inhibition of PRMT1 may be an attractive therapeutic option for liver cancer treatment.Significance:These findings show that TBX19/PRMT1 complex–mediated upregulation of MFF promotes mitochondrial fission and tumor-initiating capacity in liver cancer cells, identifying PRMT1 as a viable therapeutic target in liver cancer.

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The objective was to investigate the effect of synergistic enzymatic treatment on the properties and digestibility of a novel C-type lotus seed porous starch (LPS). Scanning electron microscopy showed that the densest and most complete pores were formed on the surface of LPS when the concentration of enzymes added was 1.5% (LS-1.5E). With increases in enzyme addition, the oil and water absorption of the porous starch increased and reached maxima at 1.5% of enzyme. Increased in the specific surface area, total pore volume and average pore diameter of LPS were determined by low-temperature nitrogen adsorption, while when the enzymes exceeded 1.5%, there were no significant changes. Compared to lotus seed starch (LS), the particle size of LPS also decreased. With the increases in enzyme addition, LPS exhibited higher relative crystallinity and ordering structure by XRD and FTIR. The results by SAXS confirmed that LPS had higher ordered semi-crystalline lamellar and denser lamellar structure compared to LS. Low-field

Mitochondrial dynamics play vital roles in the tumorigenicity and malignancy of various types of cancers by promoting the tumor-initiating potential of cancer cells, suggesting that targeting crucial factors that drive mitochondrial dynamics may lead to promising anticancer therapies. In the current study, we report that overexpression of mitochondrial fission factor (MFF), which is upregulated significantly in liver cancer–initiating cells (LCIC), promotes mitochondrial fission and enhances stemness and tumor-initiating capability in non-LCICs. MFF-induced mitochondrial fission evoked mitophagy and asymmetric stem cell division and promoted a metabolic shift from oxidative phosphorylation to glycolysis that decreased mitochondrial reactive oxygen species (ROS) production, which prevented ROS-mediated degradation of the pluripotency transcription factor OCT4. CRISPR affinity purification in situ of regulatory elements showed that T-box transcription factor 19 (TBX19), which is overexpressed uniquely in LCICs compared with non-LCICs and liver progenitor cells, forms a complex with PRMT1 on the MFF promoter in LCICs, eliciting epigenetic histone H4R3me2a/H3K9ac-mediated transactivation of MFF. Targeting PRMT1 using furamidine, a selective pharmacologic inhibitor, suppressed TBX19-induced mitochondrial fission, leading to a profound loss of self-renewal potential and tumor-initiating capacity of LCICs. These findings unveil a novel mechanism underlying mitochondrial fission–mediated cancer stemness and suggest that regulation of mitochondrial fission via inhibition of PRMT1 may be an attractive therapeutic option for liver cancer treatment. Significance: These findings show that TBX19/PRMT1 complex–mediated upregulation of MFF promotes mitochondrial fission and tumor-initiating capacity in liver cancer cells, identifying PRMT1 as a viable therapeutic target in liver cancer.

Motivated by recent applications of the open quantum system formalism to understand quarkonium transport in the quark-gluon plasma, we develop a set of coupled Boltzmann equations for open heavy quark-antiquark pairs and quarkonia. Our approach keeps track of the correlation between the heavy quark-antiquark pair from quarkonium dissociation and thus is able to account for both uncorrelated and correlated recombination. By solving the coupled Boltzmann equations for current heavy ion collision experiments, we find correlated recombination is crucial to describe the data of bottomonia nuclear modification factors. To further test the importance of correlated recombination in experiments, we propose a new observable: $\frac{R_{AA}[\chi_b(1P)]}{R_{AA}[\Upsilon(2S)]}$. Future measurements of this ratio will help distinguish calculations with and without correlated recombination., Comment: 5 pages, 2 figures; proceedings for 10th International Conference on Hard and Electromagnetic Probes of High-Energy Nuclear Collisions (Hard Probe 2020)

Background Breast cancer (BC) has a marked tendency to spread to the bone, resulting in significant skeletal complications and mortality. Recently, circular RNAs (circRNAs) have been reported to contribute to cancer initiation and progression. However, the function and mechanism of circRNAs in BC bone metastasis (BC-BM) remain largely unknown. Methods Bone-metastatic circRNAs were screened using circRNAs deep sequencing and validated using in situ hybridization in BC tissues with or without bone metastasis. The role of circIKBKB in inducing bone pre-metastatic niche formation and bone metastasis was determined using osteoclastogenesis, immunofluorescence and bone resorption pit assays. The mechanism underlying circIKBKB-mediated activation of NF-κB/bone remodeling factors signaling and EIF4A3-induced circIKBKB were investigated using RNA pull-down, luciferase reporter, chromatin isolation by RNA purification and enzyme-linked immunosorbent assays. Results We identified that a novel circRNA, circIKBKB, was upregulated significantly in bone-metastatic BC tissues. Overexpressing circIKBKB enhanced the capability of BC cells to induce formation of bone pre-metastatic niche dramatically by promoting osteoclastogenesis in vivo and in vitro. Mechanically, circIKBKB activated NF-κB pathway via promoting IKKβ-mediated IκBα phosphorylation, inhibiting IκBα feedback loop and facilitating NF-κB to the promoters of multiple bone remodeling factors. Moreover, EIF4A3, acted acting as a pre-mRNA splicing factor, promoted cyclization of circIKBKB by directly binding to the circIKBKB flanking region. Importantly, treatment with inhibitor eIF4A3-IN-2 reduced circIKBKB expression and inhibited breast cancer bone metastasis effectively. Conclusion We revealed a plausible mechanism for circIKBKB-mediated NF-κB hyperactivation in bone-metastatic BC, which might represent a potential strategy to treat breast cancer bone metastasis.

The incidence of bone metastases in hepatocellular carcinoma (HCC) has increased prominently over the past decade owing to the prolonged overall survival of HCC patients. However, the mechanisms underlying HCC bone‐metastasis remain largely unknown. In the current study, HCC‐secreted lectin galactoside‐binding soluble 3 (LGALS3) is found to be significantly upregulated and correlates with shorter bone‐metastasis‐free survival of HCC patients. Overexpression of LGALS3 enhances the metastatic capability of HCC cells to bone and induces skeletal‐related events by forming a bone pre‐metastatic niche via promoting osteoclast fusion and podosome formation. Mechanically, ubiquitin ligaseRNF219‐meidated α‐catenin degradation prompts YAP1/β‐catenin complex‐dependent epigenetic modifications of LGALS3 promoter, resulting in LGALS3 upregulation and metastatic bone diseases. Importantly, treatment with verteporfin, a clinical drug for macular degeneration, decreases LGALS3 expression and effectively inhibits skeletal complications of HCC. These findings unveil a plausible role for HCC‐secreted LGALS3 in pre‐metastatic niche and can suggest a promising strategy for clinical intervention in HCC bone‐metastasis., Hepatocellular carcinoma (HCC)‐secreted LGALS3 induces osteolytic bone metastasis (BM) via promoting osteoclast fusion and podosome formation. Mechanistically, RNF219‐mediated α‐catenin degradation results in YAP1/β‐catenin‐dependent epigenetic modifications on LGALS3 promoter, eliciting in LGALS3 upregulation in HCC. Blocking YAP1/β‐catenin complex formation on LGALS3 promoter via verteporfin reduces LGALS3 expression and effectively inhibits HCC bone‐metastasis (HCC‐BM), which represents a potential strategy for HCC‐BM clinical treatment.

We develop a framework of coupled transport equations for open heavy flavor and quarkonium states, in order to describe their transport inside the quark-gluon plasma. Our framework is capable of studying simultaneously both open and hidden heavy flavor observables in heavy-ion collision experiments and can account for both, uncorrelated and correlated recombination. Our recombination implementation depends on real-time open heavy quark and antiquark distributions. We carry out consistency tests to show how the interplay among open heavy flavor transport, quarkonium dissociation and recombination drives the system to equilibrium. We then apply our framework to study bottomonium production in heavy-ion collisions. We include $\Upsilon(1S)$, $\Upsilon(2S)$, $\Upsilon(3S)$, $\chi_b(1P)$ and $\chi_b(2P)$ in the framework and take feed-down contributions during the hadronic gas stage into account. Cold nuclear matter effects are included by using nuclear parton distribution functions for the initial primordial heavy flavor production. A calibrated $2+1$ dimensional viscous hydrodynamics is used to describe the bulk QCD medium. We calculate both the nuclear modification factor $R_{\mathrm{AA}}$ of all bottomonia states and the azimuthal angular anisotropy coefficient $v_2$ of the $\Upsilon(1S)$ state and find that our results agree reasonably with experimental measurements. Our calculations indicate that correlated cross-talk recombination is an important production mechanism of bottomonium in current heavy-ion experiments. The importance of correlated recombination can be tested experimentally by measuring the ratio of $R_{\mathrm{AA}}(\chi_b(1P))$ and $R_{\mathrm{AA}}(\Upsilon(2S))$., Comment: 36 pages, 7 figures, 3 tables; v2: changed to JHEP format, added a few references; v3: uncertainty analysis added, new measurement proposal to test correlated recombination; v4: minor change in Fig.7c and relevant discussions; v5: published version; link to the major part of the code: https://github.com/4KColo/Quarkonium_cython

Using the open quantum system formalism and effective field theory of QCD, we derive the Boltzmann transport equation of quarkonium inside the quark-gluon plasma. Our derivation illuminates that the success of transport equations in quarkonium phenomenology is closely related to the separation of scales in the problem., 4 pages, 3 figures; contribution to the proceedings of XXVIIIth International Conference on Ultrarelativistic Nucleus-Nucleus Collisions (Quark Matter 2019); updated a few references

The incidence of bone metastases in hepatocellular carcinoma (HCC) has increased prominently over the past decade owing to the prolonged overall survival of HCC patients. However, the mechanisms underlying HCC bone-metastasis remain largely unknown. Herein, we reported that HCC-secreted LGALS3 induced bone metastasis and skeletal-related events by promoting formation of bone pre-metastatic niche. We demonstrated that ubiquitin ligase RNF219-meidated α-catenin degradation prompted YAP1/β-catenin-dependent epigenetic modifications of LGALS3 promoter, resulting in LGALS3 upregulation and metastatic bone diseases. Treatment with Verteporfin, a clinical drug for macular degeneration, decreased LGALS3 expression and effectively inhibited skeletal complications of HCC. These findings unveil a plausible role for HCC-secreted LGALS3 in pre-metastatic niche and could suggest a promising strategy for clinical intervention in HCC bone-metastasis.

Hard probes produced in perturbative processes are excellent probes for the study of the hot and dense QCD matter created in relativistic heavy-ion collisions. Transport theory, allowing for coupling to an evolving medium with fluctuating initial conditions, has become a powerful tool in this endeavor. However, the implementation of the Landau-Pomeranchuk-Migdal (LPM) effect for medium-induced parton bremsstrahlung and pair production poses a challenge to semiclassical transport models based on Boltzmann-type transport equations. In this work, we investigate a possible solution to approximate the LPM effect in a ``modified Boltzmann transport'' approach, including a prescription for the running coupling constant. By fixing a numerical parameter, this approach quantitatively reproduces the rates of medium-induced parton splitting predicted by the next-to-leading-log solution of the Arnold-Moore-Yaffe equation, which is valid in the deep-LPM regime of an infinite medium. We also find qualitative agreement of our implementation with calculations in a finite and expanding medium, but future improvements are necessary for added precision at small path length. This work benefits transport model-based studies and the usage of these models in the phenomenological extraction of the jet transport coefficient.

In this study, Ni/NiO binary nanoparticles are synthesized utilizing a reflux method combined with a calcination process. The average size of the nanoparticles is 5–20 nm and the Ni content is 3.55%. Both the microstructures of the Ni/NiO interface and the states of different phases have significant impacts on the magnetic properties. By tuning the temperature and the cooling field during the loop measurement, the change rule of several critical parameters such as coercivity HC and exchange bias HE was complicated in nature. Both large HE (482 Oe) and enhanced HC (1335 Oe) were observed at 5 K, mainly due to the strong coupling interaction between Ni and NiO components. For current studies of the Ni/NiO binary nanoparticles, the complex magnetic behaviors are related to (i) the ferromagnetic contribution of Ni nanoparticles, (ii) the intrinsic antiferromagnetism of the volume phase of NiO, and (iii) the spin-glass-like characteristic corresponding to the frozen disordered state at the surface of partial NiO particles. The comprehensive effect of these three magnetic structures promotes the generation of a strongly-coupled Ni/NiO binary system, and improves the magnetic performance.

We investigate the heavy flavor dynamics in the quark-gluon plasma (QGP) medium created in p-Pb collisions at the CERN Large Hadron Collider (LHC). In the (3+1)-dimensional viscous hydrodynamics model describing QGP medium, the dynamics of heavy quarks are studied in an improved Langevin framework incorporating both collisional and radiative energy loss. The hadronization of the heavy quarks is given by a hybrid model of fragmentation and recombination. We find that the in-medium evolution of charm quarks raises the D-meson R p P b at low transverse momenta while it suppresses the D-meson R p P b at intermediate momenta. In addition, the elliptic flow of D-meson is calculated. For a diffusion coefficient which reproduces central RAA data at the LHC, we find a much smaller D-meson ν 2 compared to the light hadrons. This observation indicates an incomplete coupling between heavy quarks with the medium, due to the reduced medium size compared to AA collisions.

The heavy-flavor transport coefficients contain important information on the strong interaction at finite temperatures. The extraction of these numbers from experimental data requires dynamical modeling of heavy-flavor transport that is coupled to realistic medium evolution. Furthermore, meaningful extractions necessitate both a faithful implementation of the physical inputs to be tested and the quantification of model uncertainty. For these purposes, we have developed a partonic transport model LIDO [1, 2]. It has an improved treatment of in-medium parton bremsstrahlung, which has been calibrated to theoretical calculations in a simple medium to reduce modeling uncertainty. Regarding the interaction between heavy quark and the medium, few-body perturbative scatterings are applied to large-momentum transfer (q) processes, while a diffusion equation models the dynamics of small-q processes. Such a separation restricts the explicit use of medium quasi-particles to large-q processes only. Another advantage is that deviations from the leading-order probe-medium coupling can be parametrized as an additional contribution to the diffusion constant. The heavy quark transport coefficients are then extracted with uncertainty estimation from a Bayesian analysis including both the RHIC and the LHC data. The results are found to be consistent with earlier extraction of the light-quark transport coefficients at high momentum and be comparable with lattice calculations of the heavy-flavor diffusion constant in the static limit at low momentum.

Recent progress in open-heavy-flavor measurements and future experimental upgrades are bringing heavy-flavor physics into the precision era, allowing for strong quantitative constraints on the transport properties of heavy quarks in the quark-gluon plasma. Starting from the LIDO transport model, which combines a matrix-element based linearized-Boltzmann transport and diffusion based Langevin equation, we have made two essential improvements to increase both the flexibility and physical accuracy of the model. First, we have absorbed the pQCD scatterings with small momentum transfers to the medium into the diffusion part of the LIDO model, and we have restricted the use of vacuum matrix elements to large momentum transfer processes. This study allows us to construct a model that smoothly interpolates between a pure pQCD based approach and a radiation-improved Langevin equation by tuning a single scale parameter. Second, the Monte-Carlo implementation of the Landau-Pomeranchuk-Migdal effect of the original model has been improved to account for multiple scatterings of gluons. The simulated radiative energy loss can be tuned to quantitatively agree with semi-analytic theory calculations both for a static (finite / infinite) medium and for a dynamic expanding medium. With such improvements, the LIDO model will greatly facilitate the extraction of heavy-quark transport coefficient from a systematic model-to-data comparison.

International audience; Heavy flavor observables provide valuable information on the properties of the hot and dense quark-gluon plasma (QGP) created in ultrarelativistic nucleus-nucleus collisions. Various microscopic models have successfully described many of the observables associated with its formation. Their transport coefficients differ, however, due to different assumptions about the underlying interaction of the heavy quarks with the plasma constituents, different initial geometries and formation times, different hadronization processes, and a different time evolution of the QGP. In this study we present the transport coefficients of these models and investigate systematically how some of these assumptions influence the heavy quark properties at the end of the QGP expansion. For this purpose we impose on these models the same initial condition and the same model for the QGP expansion and show that both have considerable influence on RAA and v2.

Several transport models have been employed in recent years to analyze heavy-flavor meson spectra in high-energy heavy-ion collisions. Heavy-quark transport coefficients extracted from these models with their default parameters vary, however, by up to a factor of 5 at high momenta. To investigate the origin of this large theoretical uncertainty, a systematic comparison of heavy-quark transport coefficients is carried out between various transport models. Within a common scheme devised for the nuclear modification factor of charm quarks in a brick medium of a quark-gluon plasma, the systematic uncertainty of the extracted drag coefficient among these models is shown to be reduced to a factor of 2, which can be viewed as the smallest intrinsic systematical error band achievable at present time. This indicates the importance of a realistic hydrodynamic evolution constrained by bulk hadron spectra and of heavy-quark hadronization for understanding the final heavy-flavor hadron spectra and extracting heavy-quark drag coefficient. The transverse transport coefficient is less constrained due to the influence of the underlying mechanism for heavy-quark medium interaction. Additional constraints on transport models such as energy loss fluctuation and transverse-momentum broadening can further reduce theoretical uncertainties in the extracted transport coefficients., Comment: 20 pages in ReVTex with 11 figures, final version to appear in PRC

Transport equations have been applied successfully to describe the quarkonium evolution inside the quark-gluon plasma, which include both plasma screening effects and recombination. We demonstrate how the quarkonium transport equation is derived from QCD by using the open quantum system framework and effective field theory. Weak coupling and Markovian approximations used in the derivation are justified from a separation of scales. By solving the equations numerically, we study the Upsilon production in heavy ion collisions., Comment: 6 pages, 1 figure; contribution to proceedings for the 18th International Conference on Hadron Spectroscopy and Structure (Hadron 2019)

In relativistic heavy-ion collisions, the production of heavy quarks at large transverse momenta is strongly suppressed compared to proton-proton collisions. In addition, an unexpectedly large azimuthal anisotropy was observed for the emission of charmed hadrons in noncentral collisions. Both observations pose challenges to the theoretical understanding of the coupling between heavy quarks and the quark-gluon plasma produced in these collisions. Transport models for the evolution of heavy quarks in a QCD medium offer the opportunity to study these effects; two of the most successful approaches are based on the linearized Boltzmann transport equation and the Langevin equation. In this work, we develop a hybrid transport model that combines the strengths of both of these approaches: Heavy quarks scatter with medium partons using matrix-elements calculated in perturbative QCD, while between these discrete hard scatterings they evolve using a Langevin equation with empirical transport coefficients to capture the nonperturbative soft part of the interaction. With the hybrid transport model coupled to a state-of-the-art event-by-event bulk evolution model based on 2+1D relativistic viscous fluid dynamics, we study the azimuthal anisotropy and nuclear modification factor of heavy quarks in Pb+Pb collisions at $\sqrt{s}=5.02$ TeV. The parameters related to heavy-flavor transport are calibrated using a Bayesian analysis comparing them to available $D$-meson and $B$-meson data at the Large Hadron Collider. Using the calibrated model, we study the implications on heavy-flavor transport properties and predict observables.

By coupling the Boltzmann transport equations of both quarkonium and open heavy quarks, we investigate their dynamical evolution inside the quark-gluon plasma and study quarkonium production in heavy ion collisions. The Boltzmann transport equation of quarkonium is derived from the open quantum system formalism and effective field theory of QCD by assuming quarkonium interacts weakly with the plasma. The dissociation and recombination terms in the Boltzmann equation are calculated in potential nonrelativistic QCD. It is shown that the combination of quarkonium dissociation, recombination, open heavy quark diffusion and energy loss can drive the system of quarkonium and open heavy quarks to detailed balance and kinetic thermalization. By solving the transport equations with initial momenta of quarkonia and heavy quarks sampled from PYTHIA and a hydrodynamic medium, we can calculate the nuclear modification factors of bottomonium and describe the data at both RHIC and LHC energies. The azimuthal angular anisotropy coefficient $v_2$ of $\Upsilon$(1S) in 5.02 TeV peripheral Pb-Pb collisions is also predicted., Comment: 5 pages, 1 figure, contribution to the proceedings of Hard Probes 2018: International Conference on Hard and Electromagnetic Probes of High-Energy Nuclear Collisions

By applying a Bayesian model-to-data analysis, we estimate the temperature and momentum dependence of the heavy quark diffusion coefficient in an improved Langevin framework. The posterior range of the diffusion coefficient is obtained by performing a Markov chain Monte Carlo random walk and calibrating on the experimental data of $D$-meson $R_{\mathrm{AA}}$ and $v_2$ in three different collision systems at RHIC and the LHC: AuAu collisions at 200 GeV, PbPb collisions at 2.76 and 5.02 TeV. The spatial diffusion coefficient is found to be consistent with lattice QCD calculations and comparable with other models' estimation. We demonstrate the capability of our improved Langevin model to simultaneously describe the $R_{\mathrm{AA}}$ and $v_2$ at both RHIC and the LHC energies, as well as the higher order flow coefficient such as $D$-meson $v_3$. We show that by applying a Bayesian analysis, we are able to quantitatively and systematically study the heavy flavor dynamics in heavy-ion collisions., 16 pages, 13 figures

We apply a Bayesian model-to-data analysis on an improved Langevin framework to estimate the temperature and momentum dependence of the heavy quark diffusion coefficient in the quark-gluon plasma (QGP). The spatial diffusion coefficient is found to have a minimum around 1-3 near Tc in the zero momentum limit, and has a non-trivial momentum dependence. With the estimated diffusion coefficient, our improved Langevin model is able to simultaneously describe the D-meson RAA and v2 in three different systems at RHIC and the LHC.

International audience; Using a Bayesian model-to-data analysis, we estimate the temperature dependence of the heavy quark diffusion coefficients by calibrating to the experimental data of D -meson R AA and v 2 in AuAu collisions ( sNN=200 GeV ) and PbPb collisions ( sNN=2.76 TeV ) [G. Xie [STAR Collaboration], Nucl. Phys. A 956, 473 (2016); A. Andronic et al. , Eur. Phys. J. C 76, no. 3, 107 (2016)]. The spatial diffusion coefficient Ds2πT is found to be mostly constraint around (1.3−1.5)Tc and is compatible with lattice QCD calculations. We demonstrate the capability of our improved Langevin model to simultaneously describe the R AA and v 2 at both RHIC and the LHC energies, as well as the feasibility to apply a Bayesian analysis to quantitatively study the heavy flavor transport in heavy-ion collisions.

The impact of non-equilibrium effects on the dynamics of heavy-ion collisions is investigated by comparing a non-equilibrium transport approach, the Parton-Hadron-String-Dynamics (PHSD), to a 2D+1 viscous hydrodynamical model, which is based on the assumption of local equilibrium and conservation laws. Starting the hydrodynamical model from the same non-equilibrium initial condition as in the PHSD, using an equivalent lQCD Equation-of-State (EoS), the same transport coefficients, i.e. shear viscosity $\eta$ and the bulk viscosity $\zeta$ in the hydrodynamical model, we compare the time evolution of the system in terms of energy density, Fourier transformed energy density, spatial and momentum eccentricities and ellipticity in order to quantify the traces of non-equilibrium phenomena. In addition, we also investigate the role of initial pre-equilibrium flow on the hydrodynamical evolution and demonstrate its importance for final state observables. We find that due to non-equilibrium effects, the event-by-event transport calculations show large fluctuations in the collective properties, while ensemble averaged observables are close to the hydrodynamical results., Comment: 19 pages, 16 figures

International audience; By applying a Bayesian model-to-data comparison, our improved Langevin transport model simultaneously describes the D -meson nuclear modification factor R AA and elliptic flow v 2 in heavy-ion collisions at both RHIC and LHC energies on an event-by-event basis. We extract the diffusion coefficients of charm quarks in a quark-gluon plasma medium and find the resulting spatial diffusion coefficient D s is compatible with lattice QCD calculations.

随着中国经济的发展，国家地位不断崛起，“汉语热”也在世界各地逐渐兴起，对外汉语教学开始成为语言教育中一个新的关注点。无论是内地还是香港，大量的国际学校开始开设中文课，家长们都希望自己的孩子可以从小就学习中文。由于学生母语并非中文，背景也参差不同，因此，使用什么方式，既可以提高学生学习的兴趣，也可以帮助学生学习汉语成为了教师关注的焦点。 本文将通过实际的汉语教学实践，介绍音乐教学法在小学对外汉语教学中的应用，并详细解释音乐教学法的使用方式，旨在把音乐作为一种载体，用更加朗朗上口的方式教学中文，以求达到更好的教学效果。 本文共分为五个章节。 第一章为引言，介绍当前对外汉语教学的大背景，提出问题。 第二章为文献综述，搜集音乐教学法的理论基础，并且联系音乐与汉语间的密切关系。 第三章将介绍音乐在教学中的应用，包括音乐的优点、教学功能和其他功能。 第四章将详细分析笔者在香港九龙小学做的一系列音乐教学实验。 第五章为总结，阐述音乐教学法的优势和认知上的误区，以及文章在写作上的限制和对音乐教学法的展望。 With the economic development, China’s position continues to rise. ’Chinese fever’ is also gradually on the rise around the world, teaching Chinese as a second language (TCSL) in language education became a new focus. Both the mainland and Hong Kong, a large number of international schools begin to offer Chinese language classes. Parents hope their children to learn Chinese from an early age. As the student’s native language is not Chinese and the background also varies, thus, using which method, not only can enhance students’ interest in learning but also can help students to learn Chinese, has become a spotlight in teaching. This article will introduce using music pedagogy in primary school TCSL class and explain in detail through the teaching practice. The purpose is that using the music as a carrier, with more catchy way to teach Chinese in order to achieve better teaching results. This paper is composed of the following five chapters. The first chapter introduces the current foreign language teaching background and asks questions. The second chapter is literature review, collecting theoretical basis of music teaching, contacts the close relationship between Chinese and music. The third chapter describes the application of music in teaching, including the advantages of music, teaching and other features. The fourth chapter will analyze a series of music teaching experiment in detail of author in Hong Kong Kowloon primary school. The fifth chapter is Summary. It describes the advantages and knowledge errors of music pedagogy, limitations on article writing and the prospect of music pedagogy.

We study how heavy quark dynamics is affected by the nature of the bulk evolution of the QCD matter, the initial condition of the system, and the treatment of elementary interactions between heavy quarks and the surrounding medium. For the same initial condition and the same QGP expansion scenario we discuss the consequences of the assumption of a local equilibrium by comparing the consequences for the nuclear modification factor and the elliptic flows of charm quarks. For this purpose we employ the parton-hadron-string dynamics (PHSD), which is an off-shell microscopic transport approach, as well as the linearized-Boltzmann (LB) scheme obtained by coarse graining the PHSD bulk and assuming local equilibrium for the interactions of the charm quarks with the bulk. The $R_{\rm AA}$ of charm quarks stemming from the later LB approach is also compared to a genuine fluid dynamics evolution initiated by the coarse grained PHSD, which allows to further assess the consequences of reducing the full n-body dynamics. We then proceed to a systematic comparison of PHSD with MC@HQ, another transport model for heavy flavors which also relies on LB approach. In particular, we investigate the consequences for the nuclear modification factor of charm quarks if we vary separately the initial heavy quark distribution function in matter, the expansion dynamics of the QGP and the elementary interactions of heavy quarks of these models. We find that the results for both models vary significantly depending on the details of the calculation. However, both models achieve very similar predictions for key heavy quark observables for certain combinations of initial condition, bulk evolution and interactions. We conclude that this ambiguity limits our ability to determine the different properties of the system based on the current set of observables., Comment: 18 pages, 10 figures