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Content-based recommendation systems play a crucial role in delivering personalized content to users in the digital world. In this work, we introduce EmbSum, a novel framework that enables offline pre-computations of users and candidate items while capturing the interactions within the user engagement history. By utilizing the pretrained encoder-decoder model and poly-attention layers, EmbSum derives User Poly-Embedding (UPE) and Content Poly-Embedding (CPE) to calculate relevance scores between users and candidate items. EmbSum actively learns the long user engagement histories by generating user-interest summary with supervision from large language model (LLM). The effectiveness of EmbSum is validated on two datasets from different domains, surpassing state-of-the-art (SoTA) methods with higher accuracy and fewer parameters. Additionally, the model's ability to generate summaries of user interests serves as a valuable by-product, enhancing its usefulness for personalized content recommendations., Comment: Under review

To reveal the pore clogging law of porous asphalt mixture, the combination study of model experiment and simulation of porous asphalt mixture clogging was conducted. The pore characteristics of the porous asphalt mixture were analyzed based on the CT-scanning and discrete element software PFC3D V5. 0, and the pore data of the porous asphalt mixture were obtained. The aggregates of different particle sizes were put into PFC3D V5. 0, and the compacted virtual specimens were generated according to the pore characteristics. The accuracy of the model was verified by comparing the pore images of actual specimens with the MATLAB slices. In the self-weight condition, the simulation was set with the porous asphalt mixture specimen being intruded by clogging particles with specific gradation composition. The data of indoor experiments were compared and verified. The particle sizes of clogging particles were changed, and the pore decay rates of the specimen were analyzed. The clogging-sensitive particles were identified. In the self-weight condition, the fluid simulation experiment was introduced, and the change law of specimen clogging was analyzed by changing the seepage rate of fluid. Analysis results show that the virtual specimen generated by PFC3D V5. 0 has high accuracy, and the simulation reveals the clogging law of the specimen. The small particles not only accumulate at the throat position causing clogging, but also congregate and interlock with the particles of larger sizes resulting in clogging too. In the self-weight condition, the clogging is mainly concentrated at the upper 30 mm of the mixture specimen, and the size distribution of corresponding clogging-sensitive particles is 0. 150-0. 600 mm. The size distribution of clogging particles has a great impact on the clogging results. In the conditions of gravity and fluid, with the seepage rate increasing from 0. 005 m • s-1 to 0. 030 m • s-1, the changing rate of pore decay rate increases. In addition, the cloggi, QC 20230711

Information spread through social networks is ubiquitous. Influence maximiza- tion (IM) algorithms aim to identify individuals who will generate the greatest spread through the social network if provided with information, and have been largely devel- oped with marketing in mind. In social networks with community structure, which are very common, IM algorithms focused solely on maximizing spread may yield signifi- cant disparities in information coverage between communities, which is problematic in settings such as public health messaging. While some IM algorithms aim to remedy disparity in information coverage using node attributes, none use the empirical com- munity structure within the network itself, which may be beneficial since communities directly affect the spread of information. Further, the use of empirical network struc- ture allows us to leverage community detection techniques, making it possible to run fair-aware algorithms when there are no relevant node attributes available, or when node attributes do not accurately capture network community structure. In contrast to other fair IM algorithms, this work relies on fitting a model to the social network which is then used to determine a seed allocation strategy for optimal fair information spread. We develop an algorithm to determine optimal seed allocations for expected fair coverage, defined through maximum entropy, provide some theoretical guarantees under appropriate conditions, and demonstrate its empirical accuracy on both simu- lated and real networks. Because this algorithm relies on a fitted network model and not on the network directly, it is well-suited for partially observed and noisy social networks.

Ji Zhu,1,* Hang Chen,2,* Jianan Guo,2 Chen Zha,1 Dezhao Lu2 1The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, People’s Republic of China; 2School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dezhao Lu, Email ludezhao@126.comIntroduction: Atherosclerosis (AS) is the underlying cause of cardiovascular events. Endothelial cell mitochondrial damage and pyroptosis are important factors contributing to AS. Changes in internal mitochondrial conformation and increase in reactive oxygen species (ROS) lead to the disruption of mitochondrial energy metabolism, activation of the NLRP3 inflammasome and pyroptosis, which in turn affect atherogenesis by impairing endothelial function. AMPK is a core player in the regulation of cellular metabolism, not only by regulating mitochondrial homeostasis but also by regulating cellular inflammatory responses. Sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, has significant antioxidant and anti-inflammatory effects, and roles in cardiovascular protection.Purpose: In this study, we investigated whether STS plays a protective role in AS by regulating endothelial cell mitochondrial function and pyroptosis through an AMPK-dependent mitochondrial pathway.Methods and Results: Male ApoE−/− mice and HUVECs were used for the experiments. We found that STS treatment largely abrogated the upregulation of key proteins in aortic vessel wall plaques and typical pyroptosis signaling in ApoE−/− mice fed a western diet, consequently enhancing pAMPK expression, plaque stabilization, and anti-inflammatory responses. Consistently, STS pretreatment inhibited cholesterol crystallization (CC) -induced cell pyroptosis and activated pAMPK expression. In vitro, using HUVECs, we further found that STS treatment amelio

Bipartite graphs are ubiquitous across various scientific and engineering fields. Simultaneously grouping the two types of nodes in a bipartite graph via biclustering represents a fundamental challenge in network analysis for such graphs. The latent block model (LBM) is a commonly used model-based tool for biclustering. However, the effectiveness of the LBM is often limited by the influence of row and column sums in the data matrix. To address this limitation, we introduce the degree-corrected latent block model (DC-LBM), which accounts for the varying degrees in row and column clusters, significantly enhancing performance on real-world data sets and simulated data. We develop an efficient variational expectation-maximization algorithm by creating closed-form solutions for parameter estimates in the M steps. Furthermore, we prove the label consistency and the rate of convergence of the variational estimator under the DC-LBM, allowing the expected graph density to approach zero as long as the average expected degrees of rows and columns approach infinity when the size of the graph increases.

The development of alternative techniques for structural rehabilitation is of critical importance to the safety and sustainability of concrete structures suffered from corrosion of steel. The structural strengthening (SS) and impressed current cathodic protection (ICCP) are conventional methods to improve the safety and sustainability of corroded concrete structures at different perspectives. The SS can recover the load-carrying capacity of deteriorated concrete structures, while the ICCP can retard the corrosion of steel in concrete. Currently, a new strategy to integrate ICCP with SS has been proposed that is termed as ICCP-SS intervention system. Fabric reinforced cementitious matrix (FRCM) composites have emerged as an alternative reinforcement material to fiber reinforced polymer (FRP) composites for structural strengthening and rehabilitation. The carbon-FRCM composite can be adopted as the dual-functional material in the ICCP-SS system in which carbon- FRCM plays the role of reinforcement material in the SS system and of anode material in the ICCP system. To this end, an experimental program was undertaken to propel the application and optimization of the ICCP-SS intervention system. This study aims to clarify the characterization of RC beams with externally bonded carbon- FRCM under static and cyclic loading. Two carbon-FRCM composites were considered for this research, one with multilayer carbon-FRCM (M/C-FRCM) intended for understanding the effectiveness of carbon-FRCM in strengthening beams and one with anodically polarized carbon- FRCM (AP/C-FRCM) for evaluating the mechanical degradation caused by anodic polarization in the ICCP on the strengthening characterization of RC beams. From the material perspective, the mechanical properties of both M/C-FRCM and AP/C-FRCM composites were also studied. The first study investigates the static performance of RC beams with externally bonded M/CFRCM. The static tensile tests of M/C-FRCM were conducted, followed by

A sustainable repair method, which is called ICCP-SS (impressed current cathodic protection and structural strengthening), has been proposed for deficient reinforced concrete structures caused by corrosion of steel in concrete. In the implementation of the proposed method, a material that plays a dual functional role as structural reinforcement and impressed current anode should be used and applied on concrete substrate. A multifunctional fabric reinforced cementitious matrix (MFRCM) composite in which carbon fabric is incorporated is employed as such a functional material. While the MFRCM composite works in an ICCP-SS system the embedded carbon fabric is subjected to not only anodic polarization that is related to electrochemistry but also the stress transferred from the surrounding matrix. Thus, there is a need to investigate the bond behavior and degradation of carbon fabric embedded in the matrix under anodic polarization, which helps gain an in-depth understanding of the global behavior of MFRCM composites and the effectiveness and efficiency of the ICCP-SS method. Systematic research work was carried out, with a major aim at clarifying the bond behavior at the interface between carbon fabric and cementitious matrix within MFRCM composites under anodic polarization. In the beginning, the bond behavior of carbon yarn embedded in a range of cementitious matrices was investigated. The bond slip relationship was determined for the carbon yarn embedded in various matrices. The results show that the carbon yarns embedded in various matrices feature a similar bond behavior that can be represented by a trilinear bond slip relationship. Once the tensile strength is attained, fracture of the embedded carbon yarn can take place. An approach was derived to calculate the critical embedment length based on the bond slip relationship. Afterwards, the effect of matrix impregnation on the bond behavior between carbon fabric and matrix was studied. The outer (impregnated) part a

Accumulating evidence indicates that patient-derived organoids (PDOs) can predict drug responses in the clinic, but the ability of PDOs to predict responses to chemoradiation in cancer patients remains an open question. Here we generate a living organoid biobank from patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (NACR) enrolled in a phase III clinical trial. Our co-clinical trial data confirm that rectal cancer organoids (RCOs) closely recapitulate the pathophysiology and genetic changes of corresponding tumors. Chemoradiation responses in patients are highly matched to RCO responses, with 84.43% accuracy, 78.01% sensitivity, and 91.97% specificity. These data imply that PDOs predict LARC patient responses in the clinic and may represent a companion diagnostic tool in rectal cancer treatment.

La ETSII dispone de un antiguo laboratorio adscrito a la Unidad Docente de Termotecnia donde se realizaban ensayos de rendimiento de calderas de gasóleo. La popularización de las calderas de condensación de gas y la legislación medioambiental supuso un revés para el laboratorio. Por ello desde hace varios años la Unidad Docente de Termotecnia se encuentra inmerso en un proyecto de reconversión de las instalaciones con un fin didáctico y un fin industrial para la ampliar la gama de equipos que se pueden ensayar en el laboratorio. Uno de esos equipos son las calderas de condensación de gas. Para ello se dispone de un circuito hidráulico al que se llamará circuito o lazo de calor a partir de ahora. Dicho circuito está específicamente diseñado para medir el rendimiento de la caldera de gas. La idea fundamental es medir la potencia térmica extraída por el circuito hidráulico y compararla con la energía química de reacción de la combustión. Sabiendo esto, el equipo de desarrollo diseñará una primera versión funcional de un sistema SCADA. Para ello se emplearán los sistemas PXI de National Intruments y el software de LabVIEW. Se trata por tanto de un proyecto profesional que contará con la ayuda de ingeniero técnico de telecomunicaciones para las labores de automatización. Participarán también dos alumnos de la ETSII que tendrán como objetivo formarse en LabVIEW, ayudar en tareas de depuración de código, realizar tareas de calibración y documentar la experiencia adquirida en forma de una memoria para un Trabajo de Fin de Grado. Los tutores colaborarán con el equipo de desarrollo para la especificación de requisitos de software y ofrecerán soporte para realizar cualquier consulta relacionada con el proyecto. Como se ha comentado en el párrafo anterior, este documento solamente trata el lazo de calor. Paralelamente a este proyecto se desarrollará otro de características similares en la que se analiza el homólogo de frío y que dispone de una enfriadora. Los equipos de lazo de

Accumulating evidence indicates that patient-derived organoids (PDOs) can predict drug responses in the clinic, but the ability of PDOs to predict responses to chemoradiation in cancer patients remains an open question. Here we generate a living organoid biobank from patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (NACR) enrolled in a phase III clinical trial. Our co-clinical trial data confirm that rectal cancer organoids (RCOs) closely recapitulate the pathophysiology and genetic changes of corresponding tumors. Chemoradiation responses in patients are highly matched to RCO responses, with 84.43% accuracy, 78.01% sensitivity, and 91.97% specificity. These data imply that PDOs predict LARC patient responses in the clinic and may represent a companion diagnostic tool in rectal cancer treatment.

In this paper, we propose a flexible model for survival analysis using neural networks along with scalable optimization algorithms. One key technical challenge for directly applying maximum likelihood estimation (MLE) to censored data is that evaluating the objective function and its gradients with respect to model parameters requires the calculation of integrals. To address this challenge, we recognize that the MLE for censored data can be viewed as a differential-equation constrained optimization problem, a novel perspective. Following this connection, we model the distribution of event time through an ordinary differential equation and utilize efficient ODE solvers and adjoint sensitivity analysis to numerically evaluate the likelihood and the gradients. Using this approach, we are able to 1) provide a broad family of continuous-time survival distributions without strong structural assumptions, 2) obtain powerful feature representations using neural networks, and 3) allow efficient estimation of the model in large-scale applications using stochastic gradient descent. Through both simulation studies and real-world data examples, we demonstrate the effectiveness of the proposed method in comparison to existing state-of-the-art deep learning survival analysis models. The implementation of the proposed SODEN approach has been made publicly available at https://github.com/jiaqima/SODEN.

Qijue Lu,* Xinyu Wang,* Ji Zhu,* Xiang Fei, Hezhong Chen, Chunguang Li Department of Thoracic Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunguang LiDepartment of Thoracic Surgery, Changhai Hospital, The Second Military Medical University, No. 168 Changhai Road, Shanghai 200433, People’s Republic of ChinaTel +86 2131161764Email dr_lichunguang@sina.comIntroduction: Hypoxia and tumor-associated macrophage (TAM) are key regulators in remodeling the microenvironment of esophageal squamous cell carcinoma (ESCC). Hypoxia could stimulate tumor cells to secrete more exosomes and activate TAMs to M2 type. Here, we investigated the function and the underlying mechanism of tumor-derived exosomal hsa-circ-0048117 in TAM polarization in ESCC. Collectively, these data indicate that PC cells generate miR-301a-3p-rich exosomes in a hypoxic microenvironment, which then polarize macrophages to promote malignant behaviors of PC cells.Methods: Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were used to analyze the physical characteristics of exosomes. High-throughput sequencing and bioinformatic analysis were performed to screen the potential exosomal circRNA. FISH, Ago2 RIP, pull-down and dual-luciferase reporter assay were conducted to figure out the correlation among hsa-circ-0048117, miR-140 and toll-like receptor 4 (TLR4). Flow cytometry and Western blot were used to evaluate their joint effect in macrophages polarization. Then, the invasion and migration ability were evaluated by transwell experiment. At last, serum exo-hsa-circ-0048117 in ESCC patients was compared and the correlation between its expression and T stage, N stage and TNM grades was analyzed.Results: Hsa-circ-0048117 was significantly upregulated and enriched in exosomes secreted by hypoxia pre-challenged tumor cells and contributed to M2 ma

Huang L, Li G, Zhu J, Li Z, Li T, Leng X. Onco Targets Ther. 2020;13:3289. Due to a processing error the link for the British Medical Journal Open (BMJ Open) article described was missing. The link for the BMJ Open article has been provided here: http://dx.doi.org/10.1136/bmjopen-2018-024473. Read the original article   Read the Expression of Concern

Huang L, Li G, Zhu J, Li Z, Li T, Leng X. Efficacy of sorafenib after liver transplantation in patients with primary hepatic carcinoma exceeding the Milan criteria: a preliminary study. Onco Targets Ther. 2012;5:457– 462. The Editor-in-Chief and Publisher of OncoTargets and Therapy wish to issue an Expression of Concern for the published article. Concerns have been raised that the study described in the article did not adhere to ethical guidelines as outlined in the Declaration of Helsinki and the Declaration of Istanbul and guidance from the World Health Organization and the World Medical Association regarding the source of transplanted human organs. Specifically, the British Medical Journal Open (BMJ Open) published an article highlighting many papers in which there is concern that transplanted organs were harvested from executed prisoners in China. In response to these concerns we contacted the authors to clarify the source of the transplanted organs received by the patients described in their study. However, despite multiple attempts to contact the authors and their institutions, no response was received. The Editors of OncoTargets and Therapy would like to alert readers of this. We will provide an update if we receive any further information. OncoTargets and Therapy publishes research adhering to internationally accepted ethical standards and is committed to upholding the Declaration of Helsinki and Declaration of Istanbul. Dove Medical Press endorses the ethics guidelines described by the World Health Organization (WHO) and the World Medical Association (WMA). Read the original article Erratum for this Expression of Concern has been published&nbsp

Graphical models are commonly used to represent conditional dependence relationships between variables. There are multiple methods available for exploring them from high-dimensional data, but almost all of them rely on the assumption that the observations are independent and identically distributed. At the same time, observations connected by a network are becoming increasingly common, and tend to violate these assumptions. Here we develop a Gaussian graphical model for observations connected by a network with potentially different mean vectors, varying smoothly over the network. We propose an efficient estimation algorithm and demonstrate its effectiveness on both simulated and real data, obtaining meaningful and interpretable results on a statistics coauthorship network. We also prove that our method estimates both the inverse covariance matrix and the corresponding graph structure correctly under the assumption of network “cohesion”, which refers to the empirically observed phenomenon of network neighbors sharing similar traits.

Impressed current cathodic protection (ICCP) is an efficient method to prevent further corrosion of the re-bars, while strengthening structures (SS) by using carbon fiber mesh can help improve the loading capacity of the degraded sea-sand reinforced concrete (RC) structures. This study proposes a new dual-functional method, ICCP-SS, to retrofit the sea-sand RC structures by using the carbon - fiber reinforced cementitious matrix (C-FRCM). The C-FRCM composite, comprised of carbon fiber mesh and inorganic cementitious material, is both the anodic material in the ICCP process as well as the structural strengthening material. This paper presents an experimental program consisting of 11 simply supported beams, 10 of them casted by simulated sea-sand and subjected to accelerated corrosion process for 130 days. The specimens casted by sea-sand were afterwards bonded with C-FRCM composite, treated by ICCP for 130 days, and finally tested. In this study, the flexure strength of the beams, the deflection and curvature of the specimens, as well as the strain and the open circuit potential of re-bars are obtained and used to assess the performance of the repaired specimens. The proposed technique has been shown to be effective in retarding the corrosion of re-bars and recovering the loading capacity of the corroded specimens, which should be beneficial for the durability of sea-sand RC structures.

Hui Zhang,1,2,* Yun Deng,1–3,* Liping Liang,1,2 Lijun Shen,1,2 Ji Zhu,1,2 Yaqi Wang,1,2 Jing Zhang,1,2 Zhen Zhang1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen ZhangDepartment of Radiotherapy, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, People’s Republic of ChinaTel +86-21-64175590-5210Fax +86-21-64174774Email zhen_zhang@fudan.edu.cnPurpose: Biomarkers that predict radiosensitivity are essential for personalized radiotherapy. We performed microarray analysis for rectal cancer patients between those with good response and poor response to preoperative radiotherapy and found that patients with lower expression of tripartite motif-containing protein 31 (TRIM31) showed a better response. In this study, we confirmed the effects of TRIM31 on radiosensitivity by knockdown of TRIM31 in colorectal cancer cells.Methods and materials: Human colorectal cancer cell lines HT-29 and SW480, which are TRIM31 stably knocked-down, were used for analysis. We studied the level of DNA damage and the change of relative proteins after irradiation in TRIM31-knockdown cells. Flow cytometry was used to test for apoptosis, cell cycle stage, and reactive oxygen species (ROS) levels after irradiation. Cell survival was measured by cloning assay. Proteins related to DNA damage were evaluated by Western blotting.Results: The percentage of apoptotic cells and the levels of ROS were elevated, and the survival fraction was reduced in TRIM31-knockdown cells. The expression levels of the DNA damage proteins phosphorylated ataxia-telangiectasia mutation (P-ATM), DNA protein kinase

We consider a family of problems that are concerned about making predictions for the majority of unlabeled, graph-structured data samples based on a small proportion of labeled samples. Relational information among the data samples, often encoded in the graph/network structure, is shown to be helpful for these semi-supervised learning tasks. However, conventional graph-based regularization methods and recent graph neural networks do not fully leverage the interrelations between the features, the graph, and the labels. In this work, we propose a flexible generative framework for graph-based semi-supervised learning, which approaches the joint distribution of the node features, labels, and the graph structure. Borrowing insights from random graph models in network science literature, this joint distribution can be instantiated using various distribution families. For the inference of missing labels, we exploit recent advances of scalable variational inference techniques to approximate the Bayesian posterior. We conduct thorough experiments on benchmark datasets for graph-based semi-supervised learning. Results show that the proposed methods outperform the state-of-the-art models in most settings., Comment: NeurIPS 2019

In this paper, we propose an online Multi-Object Tracking (MOT) approach which integrates the merits of single object tracking and data association methods in a unified framework to handle noisy detections and frequent interactions between targets. Specifically, for applying single object tracking in MOT, we introduce a cost-sensitive tracking loss based on the state-of-the-art visual tracker, which encourages the model to focus on hard negative distractors during online learning. For data association, we propose Dual Matching Attention Networks (DMAN) with both spatial and temporal attention mechanisms. The spatial attention module generates dual attention maps which enable the network to focus on the matching patterns of the input image pair, while the temporal attention module adaptively allocates different levels of attention to different samples in the tracklet to suppress noisy observations. Experimental results on the MOT benchmark datasets show that the proposed algorithm performs favorably against both online and offline trackers in terms of identity-preserving metrics., Comment: Accepted by ECCV 2018

Yue Wu,1 Qiuguang He,2 Yuling Wei,3 Ji Zhu,1 Zhaohui He,1 Xiaodong Zhang,1 Zongduo Guo,1 Rui Xu,1 Chongjie Cheng,1 Zhijian Huang,1 Xiaochuan Sun11Department of Neurosurgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Neurosurgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Pharmacy, Chongqing Traditional Chinese Medicine Hospital, Chongqing, People’s Republic of ChinaBackground and purpose: Emerging evidence suggests that systemic inflammation is associated with the pathophysiological process of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to investigate the association of white blood cell (WBC) count and neutrophil-to-lymphocyte ratio (NLR) with the occurrence of DCI in SAH patients.Methods: A total of 122 patients diagnosed with aSAH within 72 h of onset were retrospectively enrolled. The count of WBC, neutrophil count (NC), and lymphocyte (LC) was collected on admission. Computed tomography perfusion was performed within 7 days after SAH. The occurrence of DCI was recorded during the hospitalization.Results: Among enrolled patients, 43 (35.2%) developed DCI during hospitalization. Patients who developed DCI had a higher count of WBC, NC, and NLR as well as a lower count of LC. NC and NLR were independently associated with the occurrence of DCI, while NLR was the best predictive parameter according to the receiver operating characteristic curve. Moreover, there was a strong correlation between NLR and mean cerebral blood flow, mean transit time and mean time to peak.Conclusion: Leukocytosis is an early pathology of SAH, and NLR may be a practical predictor for the occurrence of DCI in SAH patients.Keywords: aneurismal subarachnoid hemorrhage, neutrophil-to-lymphocyte ratio, cerebral blood flow, delayed cerebral ischemia

Qian Cheng,1 Tan-jun Tong,2 Zhao Li,1 Shi-hua Hu,1 Ding-bao Chen,1 Si-qi Wang,1 Ji-ye Zhu1 1Peking University Institute of Organ Transplantation, Peking University Center of Liver Cancer Diagnosis and Treatment, Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Department of Hepatobiliary Surgery, Peking University People’s Hospital, Beijing, 100044, China; 2Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, 100191, China Background: Cellular senescence-inhibited gene (CSIG) strongly prolongs the progression of replicative senescence. However, roles and mechanisms of CSIG in tumor progression have not been studied widely. Methods: Roles of CSIG in migration and proliferation of SMMC7721 and Huh7 cells were analyzed by transwell or cell viability assays, respectively. Tumorigenicity assays were used to study whether CSIG knockdown could affect SMMC7721 proliferation in vivo. Next, Western blotting and RT-PCR were preformed to evaluate the effects of CSIG on P-ERK cascade and epithelial mesenchymal transformation markers. Then, the location and expression of CSIG protein was detected by immunofluorescence and Western blotting, respectively. Finally, the Cancer Genome Atlas dataset was used to analyze CSIG mRNA levels in hepatocellular carcinoma (HCC) and adjacent non-tumor tissues. Results: In this study, we found that CSIG overexpression promoted SMMC7721 cell migration, and CSIG knockdown suppressed tumorigenicity of SMMC7721 cells. In contrast to expectation, CSIG up-regulation could significantly inhibit Huh7 cell growth and migration. CSIG could promote P-ERK activation and levels of mesenchymal-like markers in SMMC7721 cells, whereas CSIG suppressed P-ERK activation and levels of mesenchymal-like markers in Huh7 cells. CSIG protein was located in nucleoli as well as nucleoplasm of SMMC7721 cells, whereas CSIG protein was mainly

Modern bio-technologies have produced a vast amount of high-throughput data with the number of predictors far greater than the sample size. In order to identify more novel biomarkers and understand biological mechanisms, it is vital to detect signals weakly associated with outcomes among ultrahigh-dimensional predictors. However, existing screening methods, which typically ignore correlation information, are likely to miss these weak signals. By incorporating the inter-feature dependence, we propose a covariance-insured screening methodology to identify predictors that are jointly informative but only marginally weakly associated with outcomes. The validity of the method is examined via extensive simulations and real data studies for selecting potential genetic factors related to the onset of cancer.

Link prediction in networks is typically accomplished by estimating or ranking the probabilities of edges for all pairs of nodes. In practice, especially for social networks, the data are often collected by egocentric sampling, which means selecting a subset of nodes and recording all of their edges. This sampling mechanism requires different prediction tools than the typical assumption of links missing at random. We propose a new computationally efficient link prediction algorithm for egocentrically sampled networks, which estimates the underlying probability matrix by estimating its row space. For networks created by sampling rows, our method outperforms many popular link prediction and graphon estimation techniques.

The Expectation-Maximization (EM) algorithm is an iterative method to maximize the log-likelihood function for parameter estimation. Previous works on the convergence analysis of the EM algorithm have established results on the asymptotic (population level) convergence rate of the algorithm. In this paper, we give a data-adaptive analysis of the sample level local convergence rate of the EM algorithm. In particular, we show that the local convergence rate of the EM algorithm is a random variable K¯n derived from the data generating distribution, which adaptively yields the convergence rate of the EM algorithm on each finite sample data set from the same population distribution. We then give a non-asymptotic concentration bound of K¯n on the population level optimal convergence rate κ¯ of the EM algorithm, which implies that K¯n→κ¯ in probability as the sample size n→∞. Our theory identifies the effect of sample size on the convergence behavior of sample EM sequence, and explains a surprising phenomenon in applications of the EM algorithm, i.e. the finite sample version of the algorithm sometimes converges faster even than the population version. We apply our theory to the EM algorithm on three canonical models and obtain specific forms of the adaptive convergence theorem for each model.

In online convex optimization, adaptive algorithms, which can utilize the second-order information of the loss function's (sub)gradient, have shown improvements over standard gradient methods. This paper presents a framework Follow the Bregman Divergence Leader that unifies various existing adaptive algorithms from which new insights are revealed. Under the proposed framework, two simple adaptive online algorithms with improvable performance guarantee are derived. Furthermore, a general equation derived from a matrix analysis generalizes the adaptive learning to nonlinear case with kernel trick. © 2016 IEEE.

In online convex optimization, adaptive algorithms, which can utilize the second-order information of the loss function's (sub)gradient, have shown improvements over standard gradient methods. This paper presents a framework Follow the Bregman Divergence Leader that unifies various existing adaptive algorithms from which new insights are revealed. Under the proposed framework, two simple adaptive online algorithms with improvable performance guarantee are derived. Furthermore, a general equation derived from a matrix analysis generalizes the adaptive learning to nonlinear case with kernel trick. © 2016 IEEE.

Bin Yu,1,2,* Ye Wang,3,* Xinlu Yu,1,* Hongxia Zhang,1 Ji Zhu,4 Chen Wang,1 Fei Chen,1 Changcheng Liu,1 Jingqiang Wang,2 Haiying Zhu1 1Department of Cell Biology, Second Military Medical University, 2State Key Laboratory of Genetic Engineering and Collaborative Innovation Center of Genetics and Development, Ministry of Education Key Laboratory of Contemporary Anthropology, Department of Genetics and Development, School of Life Sciences, Fudan University, 3Department of Urinary Surgery, 4Department of Plastic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China*These authors contributed equally to this work Abstract: Recent studies have shown that metal and metal oxide have a potential function in anti-tumor therapy. Our previous studies demonstrated that cuprous oxide nanoparticles (CONPs) not only selectively induce apoptosis of tumor cells in vitro but also inhibit the growth and metastasis of melanoma by targeting mitochondria with little hepatic and renal toxicities in mice. As a further study, our current research revealed that CONPs induced apoptosis of human melanoma stem cells (CD271+/high cells) in A375 and WM266-4 melanoma cell lines and could significantly suppress the expression of MITF, SOX10 and CD271 involved in the stemness maintenance and tumorigenesis of melanoma stem cells. CD271+/high cells could accumulate more CONPs than CD271-/low through clathrin-mediated endocytosis. In addition, lower dosage of CONPs exhibited good anti-melanoma effect by decreasing the cell viability, stemness and tumorigenesis of A375 and WM266-4 cells through reducing the expression of SOX10, MITF, CD271 and genes in MAPK pathway involved in tumor progression. Finally, CONPs obviously suppressed the growth of human melanoma in tumor-bearing nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice, accompanied with tumors structural necrosis and fibrosis remarkably and decreased expression of CD27

Bin Yu,1,2,* Ye Wang,3,* Xinlu Yu,1,* Hongxia Zhang,1 Ji Zhu,4 Chen Wang,1 Fei Chen,1 Changcheng Liu,1 Jingqiang Wang,2 Haiying Zhu1 1Department of Cell Biology, Second Military Medical University, 2State Key Laboratory of Genetic Engineering and Collaborative Innovation Center of Genetics and Development, Ministry of Education Key Laboratory of Contemporary Anthropology, Department of Genetics and Development, School of Life Sciences, Fudan University, 3Department of Urinary Surgery, 4Department of Plastic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China*These authors contributed equally to this work Abstract: Recent studies have shown that metal and metal oxide have a potential function in anti-tumor therapy. Our previous studies demonstrated that cuprous oxide nanoparticles (CONPs) not only selectively induce apoptosis of tumor cells in vitro but also inhibit the growth and metastasis of melanoma by targeting mitochondria with little hepatic and renal toxicities in mice. As a further study, our current research revealed that CONPs induced apoptosis of human melanoma stem cells (CD271+/high cells) in A375 and WM266-4 melanoma cell lines and could significantly suppress the expression of MITF, SOX10 and CD271 involved in the stemness maintenance and tumorigenesis of melanoma stem cells. CD271+/high cells could accumulate more CONPs than CD271-/low through clathrin-mediated endocytosis. In addition, lower dosage of CONPs exhibited good anti-melanoma effect by decreasing the cell viability, stemness and tumorigenesis of A375 and WM266-4 cells through reducing the expression of SOX10, MITF, CD271 and genes in MAPK pathway involved in tumor progression. Finally, CONPs obviously suppressed the growth of human melanoma in tumor-bearing nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice, accompanied with tumors structural necrosis and fibrosis remarkably and decreased expression of CD27

In online convex optimization, adaptive algorithms, which can utilize the second-order information of the loss function's (sub)gradient, have shown improvements over standard gradient methods. This paper presents a framework Follow the Bregman Divergence Leader that unifies various existing adaptive algorithms from which new insights are revealed. Under the proposed framework, two simple adaptive online algorithms with improvable performance guarantee are derived. Furthermore, a general equation derived from a matrix analysis generalizes the adaptive learning to nonlinear case with kernel trick. © 2016 IEEE.

Although much progress has been made in classification with high-dimensional features \citep{Fan_Fan:2008, JGuo:2010, CaiSun:2014, PRXu:2014}, classification with ultrahigh-dimensional features, wherein the features much outnumber the sample size, defies most existing work. This paper introduces a novel and computationally feasible multivariate screening and classification method for ultrahigh-dimensional data. Leveraging inter-feature correlations, the proposed method enables detection of marginally weak and sparse signals and recovery of the true informative feature set, and achieves asymptotic optimal misclassification rates. We also show that the proposed procedure provides more powerful discovery boundaries compared to those in \citet{CaiSun:2014} and \citet{JJin:2009}. The performance of the proposed procedure is evaluated using simulation studies and demonstrated via classification of patients with different post-transplantation renal functional types.

Xiao-Min Lu,* Ji-Ping Zhu,* Xian-Mei Zhou Department of Respiratory Medicine, Affiliated Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Traditional Chinese Medicine, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: Insomnia is a common comorbidity associated with COPD. Although benzodiazepines (BZDs) can have adverse effects on respiratory response in COPD patients, these are the most common hypnotics. The aim of this study was to examine by meta-analysis the efficacy and safety of BZD to treat insomnia in COPD patients. Materials and methods: Electronic databases (PubMed, China National Knowledge Infrastructure, Cochrane clinical trials database) were searched. Studies were eligible if they compared the effects of BZD versus placebo on insomnia in COPD patients. Two reviewers extracted data independently. Disagreements were resolved by discussion with another reviewer until a consensus was achieved. Data that included objective and subjective sleep evaluation and respiratory function variables were extracted. Data were analyzed by the methods recommended by Review Manager 5.3 software. Results: A total of 233 records were identified through the initial search; of these, five studies were included in the meta-analysis. When BZD was compared with placebo, objective sleep quality was significantly improved, including total sleep time (95% confidence interval [CI] 0.54–1.14, P<0.00001), sleep efficiency (95% CI 0.48–1.16, P<0.00001), sleep latency (95% CI -18.24 to -4.46, P=0.001), and number of arousals/hour of sleep (95% CI -0.72 to -0.07, P=0.02). Otherwise, subjective sleep quality was not improved remarkably. Apart from maximum transcutaneous carbon dioxide pressure increase during sleep (95% CI 0.05–0.28, P=0.006), BZD administration had no effect on respiratory assessment. Conclusion: In this meta-analysis, the results s

Many methods have been proposed for community detection in networks, but most of them do not take into account additional information on the nodes that is often available in practice. In this paper, we propose a new joint community detection criterion that uses both the network edge information and the node features to detect community structures. One advantage our method has over existing joint detection approaches is the flexibility of learning the impact of different features which may differ across communities. Another advantage is the flexibility of choosing the amount of influence the feature information has on communities. The method is asymptotically consistent under the block model with additional assumptions on the feature distributions, and performs well on simulated and real networks., Comment: 16 pages, 5 pages

Hui Zhang,1,5,* Mengyun Wang,2,5,* Tingyan Shi,2,5 Lijun Shen,1,5 Ji Zhu,1,5 Menghong Sun,3,5 Yun Deng,1,5 Liping Liang,1,5 Guichao Li,1,5 Yongxin Wu,1,5 Ming Fan,1,5 Qingyi Wei,2,4 Zhen Zhang1,5 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 3Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 4Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA; 5Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Plasminogen activator inhibitor type 1 (PAI-1) and protease-activated receptor-1 (PAR-1) are crucial mediators of the intestinal microenvironment and are involved in radiation-induced acute and chronic injury. To evaluate whether genetic polymorphisms of PAI-1 and PAR-1 were predictors of radiation-induced injury in patients with rectal cancer, we retrospectively evaluated 356 rectal cancer patients who had received pelvic radiotherapy and analyzed the association of genetic polymorphisms of PAI-1 and PAR-1 with acute toxicities after radiotherapy. Acute adverse events were scored, including dermatitis, fecal incontinence (anal toxicity), hematological toxicity, diarrhea, and vomiting. The patients were grouped into grade ≥2 and grade 0–1 toxicity groups to analyze the acute toxicities. Genotyping of six single nucleotide polymorphisms (SNPs) of PAI-1 and PAR-1 was performed using TaqMan assays. A logistic regression model was used to estimate the odds ratios and 95% confidence intervals. Of the 356 individuals, 264 (72.5%) had grade ≥2 total toxicities; within this group, there were 65 (18.3%) individuals who reached grade ≥3 toxicities. There were 19

Ph.D., Temple University--Theses, With the grant of a big CRM dataset from a large media company, this dissertation examines four different categories of factors that could impact three stages of customer relationship management, namely customer acquisition, retention, and winback of lost customers. Specifically, with the aid of machine learning method of random forests and text mining technique, this study identify among the factors of customer heterogeneity (e.g. in usage of self-care service channels, duration of service, responsiveness to marketing actions), firm's marketing initiatives (e.g. the volume of the marketing communications, the depth of the promotion, the different communication channels they use, and the marketing penetration in different geographical areas), customer self-reported deactivation reasons, as well as the call centers notes in text form, which factors play bigger roles than others during each of the three stages of CRM. Furthermore, the authors also examine how these factors evolve throughout these three stages of CRM in terms of their effects on shaping customers' decision making of whether to convert to paid customer, to churn, or to reactivate their service with the company. The findings help managers better allocate their resources in the processes of acquiring, retaining and winning back customers.

Tiejun Zhao,1 Hezhong Chen,1 Yuchao Dong,2 Jiajun Zhang,1 Haidong Huang,2 Ji Zhu,1 Wei Zhang21Institute of Cardiothoracic Surgery, 2Respiratory Department, Changhai Hospital, Shanghai, People's Republic of ChinaAbstract: In order to improve the therapeutic efficacy and minimize the side effects of lung cancer chemotherapy, the formulation of paclitaxel-loaded poly(glycolide-co-ε-caprolactone)-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles (PTX-loaded [PGA-co-PCL]-b-TPGS2k NPs) was prepared. The novel amphiphilic copolymer (PGA-co-PCL)-b-TPGS2k was synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance spectroscopy and gel permeation chromatography. The PTX-loaded (PGA-co-PCL)-b -TPGS2k NPs were characterized in terms of size, size distribution, zeta potential, drug encapsulation, surface morphology, and drug release. In vitro cellular uptakes of NPs were investigated with confocal laser scanning microscopy, indicating the coumarin 6-loaded (PGA-co-PCL)-b -TPGS2k NPs could be internalized by human lung cancer A-549 cells. The antitumor effect of PTX-loaded NPs was evaluated, both in vitro and in vivo, on an A-549 cell tumor-bearing mouse model via intratumoral injection. The commercial PTX formulation Taxol was chosen as the reference. Experimental results showed that the PTX-loaded NPs possessed higher cytotoxicity and could effectively inhibit the growth of tumor. All the results suggested that amphiphilic copolymer (PGA-co-PCL)-b -TPGS2k could act as a potential biological material for nanoformulation in the treatment of lung cancer.Keywords: (PGA-co-PCL)-b TPGS2k, paclitaxel, nanoparticles, drug delivery, lung cancer

Tiejun Zhao,1 Hezhong Chen,1 Yuchao Dong,2 Jiajun Zhang,1 Haidong Huang,2 Ji Zhu,1 Wei Zhang21Institute of Cardiothoracic Surgery, 2Respiratory Department, Changhai Hospital, Shanghai, People's Republic of ChinaAbstract: In order to improve the therapeutic efficacy and minimize the side effects of lung cancer chemotherapy, the formulation of paclitaxel-loaded poly(glycolide-co-ε-caprolactone)-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles (PTX-loaded [PGA-co-PCL]-b-TPGS2k NPs) was prepared. The novel amphiphilic copolymer (PGA-co-PCL)-b-TPGS2k was synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance spectroscopy and gel permeation chromatography. The PTX-loaded (PGA-co-PCL)-b -TPGS2k NPs were characterized in terms of size, size distribution, zeta potential, drug encapsulation, surface morphology, and drug release. In vitro cellular uptakes of NPs were investigated with confocal laser scanning microscopy, indicating the coumarin 6-loaded (PGA-co-PCL)-b -TPGS2k NPs could be internalized by human lung cancer A-549 cells. The antitumor effect of PTX-loaded NPs was evaluated, both in vitro and in vivo, on an A-549 cell tumor-bearing mouse model via intratumoral injection. The commercial PTX formulation Taxol was chosen as the reference. Experimental results showed that the PTX-loaded NPs possessed higher cytotoxicity and could effectively inhibit the growth of tumor. All the results suggested that amphiphilic copolymer (PGA-co-PCL)-b -TPGS2k could act as a potential biological material for nanoformulation in the treatment of lung cancer.Keywords: (PGA-co-PCL)-b TPGS2k, paclitaxel, nanoparticles, drug delivery, lung cancer

This paper presents an asynchronous distributed algorithm to manage multiple trees for peer-to-peer streaming in a flow level model. It is assumed that videos are cut into substreams, with or without source coding, to be distributed to all nodes. The algorithm guarantees that each node receives sufficiently many substreams within delay logarithmic in the number of peers. The algorithm works by constantly updating the topology so that each substream is distributed through trees to as many nodes as possible without interference. Competition among trees for limited upload capacity is managed so that both coverage and balance are achieved. The algorithm is robust in that it efficiently eliminates cycles and maintains tree structures in a distributed way. The algorithm favors nodes with higher degree, so it not only works for live streaming and video on demand, but also in the case a few nodes with large degree act as servers and other nodes act as clients. A proof of convergence of the algorithm is given assuming instantaneous update of depth information, and for the case of a single tree it is shown that the convergence time is stochastically tightly bounded by a small constant times the log of the number of nodes. These theoretical results are complemented by simulations showing that the algorithm works well even when most assumptions for the theoretical tractability do not hold.

Link prediction is one of the fundamental problems in network analysis. In many applications, notably in genetics, a partially observed network may not contain any negative examples of absent edges, which creates a difficulty for many existing supervised learning approaches. We develop a new method which treats the observed network as a sample of the true network with different sampling rates for positive and negative examples. We obtain a relative ranking of potential links by their probabilities, utilizing information on node covariates as well as on network topology. Empirically, the method performs well under many settings, including when the observed network is sparse. We apply the method to a protein-protein interaction network and a school friendship network.

Biomaterials and neurotrophic factors represent promising guidance for neural repair. In this study, we combined poly-(lactic acid-co-glycolic acid) (PLGA) conduits and neurotrophin-3 (NT-3) to generate NT-3-loaded PLGA carriers in vitro. Bioactive NT-3 was released stably and constantly from PLGA conduits for up to 4 weeks. Neural stem cells (NSCs) and Schwann cells (SCs) were coseeded into an NT-releasing scaffold system and cultured for 14 days. Immunoreactivity against Map2 showed that most of the grafted cells (>80%) were differentiated toward neurons. Double-immunostaining for synaptogenesis and myelination revealed the formation of synaptic structures and myelin sheaths in the coculture, which was also observed under electron microscope. Furthermore, under depolarizing conditions, these synapses were excitable and capable of releasing synaptic vesicles labeled with FM1-43 or FM4-64. Taken together, coseeding NSCs and SCs into NT-3-loaded PLGA carriers increased the differentiation of NSCs into neurons, developed synaptic connections, exhibited synaptic activities, and myelination of neurites by the accompanying SCs. These results provide an experimental basis that supports transplantation of functional neural construction in spinal cord injury.

Biomaterials and neurotrophic factors represent promising guidance for neural repair. In this study, we combined poly-(lactic acid-co-glycolic acid) (PLGA) conduits and neurotrophin-3 (NT-3) to generate NT-3-loaded PLGA carriers in vitro. Bioactive NT-3 was released stably and constantly from PLGA conduits for up to 4 weeks. Neural stem cells (NSCs) and Schwann cells (SCs) were coseeded into an NT-releasing scaffold system and cultured for 14 days. Immunoreactivity against Map2 showed that most of the grafted cells (>80%) were differentiated toward neurons. Double-immunostaining for synaptogenesis and myelination revealed the formation of synaptic structures and myelin sheaths in the coculture, which was also observed under electron microscope. Furthermore, under depolarizing conditions, these synapses were excitable and capable of releasing synaptic vesicles labeled with FM1-43 or FM4-64. Taken together, coseeding NSCs and SCs into NT-3-loaded PLGA carriers increased the differentiation of NSCs into neurons, developed synaptic connections, exhibited synaptic activities, and myelination of neurites by the accompanying SCs. These results provide an experimental basis that supports transplantation of functional neural construction in spinal cord injury.

Yi Xiong1,*, Ji-Xiang Zhu2,*, Zheng-Yu Fang1, Cheng-Guang Zeng2, Chao Zhang1, Guo-Long Qi3, Man-Hui Li1, Wei Zhang1, Da-Ping Quan2, Jun Wan1,41Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Shenzhen, 2DSAPM Lab, PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, 3Department of Medical Information, Medical Collage of Jinan University, Guangzhou, 4Division of Life Science, the Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China*These authors contributed equally to this manuscriptAbstract: Biomaterials and neurotrophic factors represent promising guidance for neural repair. In this study, we combined poly-(lactic acid-co-glycolic acid) (PLGA) conduits and neurotrophin-3 (NT-3) to generate NT-3-loaded PLGA carriers in vitro. Bioactive NT-3 was released stably and constantly from PLGA conduits for up to 4 weeks. Neural stem cells (NSCs) and Schwann cells (SCs) were coseeded into an NT-releasing scaffold system and cultured for 14 days. Immunoreactivity against Map2 showed that most of the grafted cells (>80%) were differentiated toward neurons. Double-immunostaining for synaptogenesis and myelination revealed the formation of synaptic structures and myelin sheaths in the coculture, which was also observed under electron microscope. Furthermore, under depolarizing conditions, these synapses were excitable and capable of releasing synaptic vesicles labeled with FM1-43 or FM4-64. Taken together, coseeding NSCs and SCs into NT-3-loaded PLGA carriers increased the differentiation of NSCs into neurons, developed synaptic connections, exhibited synaptic activities, and myelination of neurites by the accompanying SCs. These results provide an experimental basis that supports transplantation of functional neural construction in spinal cord injury.Keywords: PLGA, NT-3, neural stem cells, Schwann cells, myelin sheath

Yi Xiong1,*, Ji-Xiang Zhu2,*, Zheng-Yu Fang1, Cheng-Guang Zeng2, Chao Zhang1, Guo-Long Qi3, Man-Hui Li1, Wei Zhang1, Da-Ping Quan2, Jun Wan1,41Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Shenzhen, 2DSAPM Lab, PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, 3Department of Medical Information, Medical Collage of Jinan University, Guangzhou, 4Division of Life Science, the Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China*These authors contributed equally to this manuscriptAbstract: Biomaterials and neurotrophic factors represent promising guidance for neural repair. In this study, we combined poly-(lactic acid-co-glycolic acid) (PLGA) conduits and neurotrophin-3 (NT-3) to generate NT-3-loaded PLGA carriers in vitro. Bioactive NT-3 was released stably and constantly from PLGA conduits for up to 4 weeks. Neural stem cells (NSCs) and Schwann cells (SCs) were coseeded into an NT-releasing scaffold system and cultured for 14 days. Immunoreactivity against Map2 showed that most of the grafted cells (>80%) were differentiated toward neurons. Double-immunostaining for synaptogenesis and myelination revealed the formation of synaptic structures and myelin sheaths in the coculture, which was also observed under electron microscope. Furthermore, under depolarizing conditions, these synapses were excitable and capable of releasing synaptic vesicles labeled with FM1-43 or FM4-64. Taken together, coseeding NSCs and SCs into NT-3-loaded PLGA carriers increased the differentiation of NSCs into neurons, developed synaptic connections, exhibited synaptic activities, and myelination of neurites by the accompanying SCs. These results provide an experimental basis that supports transplantation of functional neural construction in spinal cord injury.Keywords: PLGA, NT-3, neural stem cells, Schwann cells, myelin sheath

Biomaterials and neurotrophic factors represent promising guidance for neural repair. In this study, we combined poly-(lactic acid-co-glycolic acid) (PLGA) conduits and neurotrophin-3 (NT-3) to generate NT-3-loaded PLGA carriers in vitro. Bioactive NT-3 was released stably and constantly from PLGA conduits for up to 4 weeks. Neural stem cells (NSCs) and Schwann cells (SCs) were coseeded into an NT-releasing scaffold system and cultured for 14 days. Immunoreactivity against Map2 showed that most of the grafted cells (>80%) were differentiated toward neurons. Double-immunostaining for synaptogenesis and myelination revealed the formation of synaptic structures and myelin sheaths in the coculture, which was also observed under electron microscope. Furthermore, under depolarizing conditions, these synapses were excitable and capable of releasing synaptic vesicles labeled with FM1-43 or FM4-64. Taken together, coseeding NSCs and SCs into NT-3-loaded PLGA carriers increased the differentiation of NSCs into neurons, developed synaptic connections, exhibited synaptic activities, and myelination of neurites by the accompanying SCs. These results provide an experimental basis that supports transplantation of functional neural construction in spinal cord injury.

Lei Huang, Guang-ming Li, Ji-ye Zhu, Zhao Li, Tao Li, Xi-sheng LengCenter of Hepatobiliary Surgery, Peking University People's Hospital, Peking University, Beijing, People's Republic of ChinaBackground: The purpose of this study was to determine the efficacy of sorafenib in preventing and treating tumor recurrence after liver transplantation in patients with primary hepatic carcinoma exceeding the Milan criteria.Methods: Thirty patients with primary hepatic carcinoma exceeding the Milan criteria underwent liver transplantation at our hospital between March 2008 and June 2010. Matched for age and gender, the patients were randomized to treatment with sorafenib 400 mg bid or capecitabine (control group, 1500 mg bid, administered for 2 weeks followed by a 2-week rest interval in each cycle). Treatments were discontinued 18 months after transplantation if no recurrence occurred. Patients who experienced tumor recurrence continued their allocated treatment until they were deemed no longer suitable for the medication. Sorafenib and capecitabine were stopped or their dose was reduced in patients with severe adverse reactions.Results: The one-year recurrence rates were 53.3% and 86.6% in patients treated with sorafenib and capecitabine, respectively (χ 2 = 3.968, P < 0.05), and the one-year survival rates were 93.3% and 46.6%, respectively (χ 2 = 7.777, P < 0.05). Mean survival time was significantly longer in the sorafenib group (24.6 ± 1.7 [range 7– 28] months) than in the capecitabine group (16.4 ± 2.7 [range 5– 34], months (χ 2 = 7.154, P < 0.05). Most treatment-emergent adverse reactions in both treatment groups were of grade 1 or 2 in severity. The incidence of diarrhea and hand-foot syndrome tended to be higher in the sorafenib group.Conclusion: For patients with primary hepatic carcinoma exceeding the Milan criteria, sorafenib may reduce or delay tumor recurrence after l

There has been a lot of work fitting Ising models to multivariate binary data in order to understand the conditional dependency relationships between the variables. However, additional covariates are frequently recorded together with the binary data, and may influence the dependence relationships. Motivated by such a dataset on genomic instability collected from tumor samples of several types, we propose a sparse covariate dependent Ising model to study both the conditional dependency within the binary data and its relationship with the additional covariates. This results in subject-specific Ising models, where the subject's covariates influence the strength of association between the genes. As in all exploratory data analysis, interpretability of results is important, and we use L1 penalties to induce sparsity in the fitted graphs and in the number of selected covariates. Two algorithms to fit the model are proposed and compared on a set of simulated data, and asymptotic results are established. The results on the tumor dataset and their biological significance are discussed in detail., Comment: 32 pages (including 5 pages of appendix), 3 figures, 2 tables