Penalized Estimation of Directed Acyclic Graphs From Discrete Data

Bayesian networks, with structure given by a directed acyclic graph (DAG), are a popular class of graphical models. However, learning Bayesian networks from discrete or categorical data is particularly challenging, due to the large parameter space and the difficulty in searching for a sparse structure. In this article, we develop a maximum penalized likelihood method to tackle this problem. Instead of the commonly used multinomial distribution, we model the conditional distribution of a node given its parents by multi-logit regression, in which an edge is parameterized by a set of coefficient vectors with dummy variables encoding the levels of a node. To obtain a sparse DAG, a group norm penalty is employed, and a blockwise coordinate descent algorithm is developed to maximize the penalized likelihood subject to the acyclicity constraint of a DAG. When interventional data are available, our method constructs a causal network, in which a directed edge represents a causal relation. We apply our method to various simulated and real data sets. The results show that our method is very competitive, compared to many existing methods, in DAG estimation from both interventional and high-dimensional observational data.Comment: To appear in Statistics and Computin

Theory of magnetoelectric photocurrent generated by direct interband transitions in semiconductor quantum well

A linearly polarized light normally incident on a semiconductor quantum well with spin-orbit coupling may generate pure spin current via direct interband optical transition. An electric photocurrent can be extracted from the pure spin current when an in-plane magnetic field is applied, which has been recently observed in the InGaAs/InAlAs quantum well [Dai et al., Phys. Rev. Lett. 104, 246601 (2010)]. Here we present a theoretical study of this magnetoelectric photocurrent effect associated with the interband transition. By employing the density matrix formalism, we show that the photoexcited carrier density has an anisotropic distribution in k space, strongly dependent on the orientation of the electron wavevector and the polarization of the light. This anisotropy provides an intuitive picture of the observed dependence of the photocurrent on the magnetic field and the polarization of the light. We also show that the ratio of the pure spin photocurrent to the magnetoelectric photocurrent is approximately equal to the ratio of the kinetic energy to the Zeeman energy, which enables us to estimate the magnitude of the pure spin photocurrent. The photocurrent density calculated with the help of an anisotropic Rashba model and the Kohn-Luttinger model can produce all three terms in the fitting formula for measured current, with comparable order of magnitude, but discrepancies are still present and further investigation is needed.Comment: 13 pages, 9 figures, 2 table

Plasmacytoid Dendritic Cells and Cancer Immunotherapy

Despite largely disappointing clinical trials of dendritic cell (DC)-based vaccines, recent studies have shown that DC-mediated cross-priming plays a critical role in generating anti-tumor CD8 T cell immunity and regulating anti-tumor efficacy of immunotherapies. These new findings thus support further development and refinement of DC-based vaccines as mono-immunotherapy or combinational immunotherapies. One exciting development is recent clinical studies with naturally circulating DCs including plasmacytoid DCs (pDCs). pDC vaccines were particularly intriguing, as pDCs are generally presumed to play a negative role in regulating T cell responses in tumors. Similarly, DC-derived exosomes (DCexos) have been heralded as cell-free therapeutic cancer vaccines that are potentially superior to DC vaccines in overcoming tumor-mediated immunosuppression, although DCexo clinical trials have not led to expected clinical outcomes. Using a pDC-targeted vaccine model, we have recently reported that pDCs required type 1 conventional DCs (cDC1s) for optimal cross-priming by transferring antigens through pDC-derived exosomes (pDCexos), which also cross-prime CD8 T cells in a bystander cDC-dependent manner. Thus, pDCexos could combine the advantages of both cDC1s and pDCs as cancer vaccines to achieve better anti-tumor efficacy. In this review, we will focus on the pDC-based cancer vaccines and discuss potential clinical application of pDCexos in cancer immunotherapy

Dc-based vaccines for cancer immunotherapy

As the sentinels of the immune system, dendritic cells (DCs) play a critical role in initiating and regulating antigen-specific immune responses. Cross-priming, a process that DCs activate CD8 T cells by cross-presenting exogenous antigens onto their MHCI (Major Histocompatibility Complex class I), plays a critical role in mediating CD8 T cell immunity as well as tolerance. Current DC vaccines have remained largely unsuccessful despite their ability to potentiate both effector and memory CD8 T cell responses. There are two major hurdles for the success of DC-based vaccines: tumor-mediated immunosuppression and the functional limitation of the commonly used monocyte-derived dendritic cells (MoDCs). Due to their resistance to tumor-mediated suppression as inert vesicles, DC-derived exosomes (DCexos) have garnered much interest as cell-free therapeutic agents. However, current DCexo clinical trials have shown limited clinical benefits and failed to generate antigen-specific T cell responses. Another exciting development is the use of naturally circulating DCs instead of in vitro cultured DCs, as clinical trials with both human blood cDC2s (type 2 conventional DCs) and plasmacytoid DCs (pDCs) have shown promising results. pDC vaccines were particularly encouraging, especially in light of promising data from a recent clinical trial using a human pDC cell line, despite pDCs being considered tolerogenic and playing a suppressive role in tumors. However, how pDCs generate anti-tumor CD8 T cell immunity remains poorly understood, thus hindering their clinical advance. Using a pDC-targeted vaccine model, we have recently reported that while pDC-targeted vaccines led to strong cross-priming and durable CD8 T cell immunity, cross-presenting pDCs required cDCs to achieve cross-priming in vivo by transferring antigens to cDCs. Antigen transfer from pDCs to bystander cDCs was mediated by pDC-derived exosomes (pDCexos), which similarly required cDCs for cross-priming of antigen-specific CD8 T cells. pDCexos thus represent a new addition in our arsenal of DC-based cancer vaccines that would potentially combine the advantage of pDCs and DCexos

GKZ-system of the 2-loop self energy with 4 propagators

Applying the system of linear partial differential equations derived from Mellin-Barnes representations and Miller's transformation, we present GKZ-system of Feynman integral of the 2-loop self energy diagram with 4 propagators. The codimension of derived GKZ-system equals the number of independent dimensionless ratios among the external momentum squared and virtual mass squared. In total 536 hypergeometric functions are obtained in neighborhoods of origin and infinity, in which 30 linearly independent hypergeometric functions whose convergent regions have non-empty intersection constitute a fundamental solution system in a proper subset of the whole parameter space.Comment: latex, 299 pages, including 1 figure + 17 appendices. arXiv admin note: text overlap with arXiv:2206.0422

DC-Derived Exosomes for Cancer Immunotherapy

As the initiators of adaptive immune responses, DCs play a central role in regulating the balance between CD8 T cell immunity versus tolerance to tumor antigens. Exploiting their function to potentiate host anti-tumor immunity, DC-based vaccines have been one of most promising and widely used cancer immunotherapies. However, DC-based cancer vaccines have not achieved the promised success in clinical trials, with one of the major obstacles being tumor-mediated immunosuppression. A recent discovery on the critical role of type 1 conventional DCs (cDC1s) play in cross-priming tumor-specific CD8 T cells and determining the anti-tumor efficacy of cancer immunotherapies, however, has highlighted the need to further develop and refine DC-based vaccines either as monotherapies or in combination with other therapies. DC-derived exosomes (DCexos) have been heralded as a promising alternative to DC-based vaccines, as DCexos are more resistance to tumor-mediated suppression and DCexo vaccines have exhibited better anti-tumor efficacy in pre-clinical animal models. However, DCexo vaccines have only achieved limited clinical efficacy and failed to induce tumor-specific T cell responses in clinical trials. The lack of clinical efficacy might be partly due to the fact that all current clinical trials used peptide-loaded DCexos from monocyte-derived DCs. In this review, we will focus on the perspective of expanding current DCexo research to move DCexo cancer vaccines forward clinically to realize their potential in cancer immunotherapy

Device modeling of superconductor transition edge sensors based on the two-fluid theory

In order to support the design and study of sophisticated large scale transition edge sensor (TES) circuits, we use basic SPICE elements to develop device models for TESs based on the superfluid-normal fluid theory. In contrast to previous studies, our device model is not limited to small signal simulation, and it relies only on device parameters that have clear physical meaning and can be easily measured. We integrate the device models in design kits based on powerful EDA tools such as CADENCE and OrCAD, and use them for versatile simulations of TES circuits. Comparing our simulation results with published experimental data, we find good agreement which suggests that device models based on the two-fluid theory can be used to predict the behavior of TES circuits reliably and hence they are valuable for assisting the design of sophisticated TES circuits.Comment: 10pages,11figures. Accepted to IEEE Trans. Appl. Supercon

Sestrin 2 Attenuates Rat Hepatic Stellate Cell (HSC) Activation and Liver Fibrosis via an mTOR/AMPK-Dependent Mechanism

Background/Aims: Sestrin 2 is associated with the pathophysiology of several diseases. The aim of this study was to investigate the effects and potential mechanisms of Sestrin 2 in rat hepatic stellate cells (HSCs) during liver fibrogenesis. Methods: In this study, Sestrin 2 protein expression was detected in rat HSC-T6 cells challenged with transforming growth factor-β (TGF-β) and in mice treated with carbon tetrachloride (CCl4), a well-known model of hepatic fibrosis. Next, HSC-T6 cells and fibrotic mice were transfected with lentivirus. The mRNA expression levels of markers of liver fibrosis [alpha-smooth muscle actin (α-SMA) and collagen 1A1 (Col1A1)] were analyzed by quantitative reverse transcription–polymerase chain reaction (RT-PCR). Cell death and proliferation were evaluated by the MTT assay, and biochemical markers of liver damage in serum [alanine transaminase (ALT) and aspartate transaminase (AST)] were also measured using a biochemical analyzer. Histopathological examination was used to evaluate the degree of liver fibrosis, and protein expression [phospho-adenosine monophosphate-activated protein kinase (p-AMPK), AMPK, phospho-mammalian target of rapamycin (p-mTOR), and mTOR] was determined by western blotting. Results: We found that Sestrin 2 was elevated in both the HSC-T6 cell and hepatic fibrosis models. In vitro, overexpression of Sestrin 2 attenuated the mRNA levels of α-SMA and Col1A1, suppressed α-SMA protein expression, and modulated HSC-T6 cell proliferation. In vivo, overexpression of Sestrin 2 reduced the ALT and AST levels as well as the α-SMA and Col1A1 protein expression in the CCl4 model of liver fibrosis. Moreover, the degree of liver fibrosis was ameliorated. Interestingly, overexpression of Sestrin 2 increased p-AMPK but decreased p-mTOR protein expression. Conclusion: Our findings indicate that Sestrin 2 may attenuate the activation of HSCs and ameliorate liver fibrosis, most likely via upregulation of AMPK phosphorylation and suppression of the mTOR signaling pathway