Adenovirus-Mediated Inducible Expression of a PD-L1 Blocking Antibody in Combination with Macrophage Depletion Improves Survival in a Mouse Model of Peritoneal Carcinomatosis

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (TIM-3) or agonistic mAbs for 4-1BB (CD137). In contrast, macrophage depletion by clodronate liposomes enhanced the efficacy of HCA-EFZP-aPDL1. These results highlight the importance of addressing macrophage-associated immunoregulatory mechanisms to overcome resistance to ICIs in the context of colorectal cancer.     

Quadratic optimization fine tuning for the Support Vector Machines learning phase

This work presents a comparative analysis of specific, rather than general, mathematical programming implementation techniques of the quadratic optimization problem (QP) based on Support Vector Machines (SVM) learning process. Considering the Karush–Kuhn–Tucker (KKT) optimality conditions, we present a strategy of implementation of the SVM-QP following three classical approaches: (i) active set, also divided in primal and dual spaces, methods, (ii) interior point methods and (iii) linearization strategies. We also present the general extension to treat large-scale applications consisting in a general decomposition of the QP problem into smaller ones, conserving the exact solution approach. In the same manner, we propose a set of heuristics to take into account for a better than a random selection process for the initialization of the decomposition strategy. We compare the performances of the optimization strategies using some well-known benchmark databases.     

Computer aided detection system for micro calcifications in digital mammograms

Breast cancer continues to be a significant public health problem in the world. Early detection is the key for improving breast cancer prognosis. Mammogram breast X-ray is considered the most reliable method in early detection of breast cancer. However, it is difficult for radiologists to provide both accurate and uniform evaluation for the enormous mammograms generated in widespread screening. Micro calcification clusters (MCCs) and masses are the two most important signs for the breast cancer, and their automated detection is very valuable for early breast cancer diagnosis. The main objective is to discuss the computer-aided detection system that has been proposed to assist the radiologists in detecting the specific abnormalities and improving the diagnostic accuracy in making the diagnostic decisions by applying techniques splits into three-steps procedure beginning with enhancement by using Histogram equalization (HE) and Morphological Enhancement, followed by segmentation based on Otsu's threshold the region of interest for the identification of micro calcifications and mass lesions, and at last classification stage, which classify between normal and micro calcifications ‘patterns and then classify between benign and malignant micro calcifications. In classification stage; three methods were used, the voting K-Nearest Neighbor classifier (K-NN) with prediction accuracy of 73%, Support Vector Machine classifier (SVM) with prediction accuracy of 83%, and Artificial Neural Network classifier (ANN) with prediction accuracy of 77%.     

Automatic classification and prediction models for early Parkinson’s disease diagnosis from SPECT imaging

Early and accurate diagnosis of Parkinson’s disease (PD) is important for early management, proper prognostication and for initiating neuroprotective therapies once they become available. Recent neuroimaging techniques such as dopaminergic imaging using single photon emission computed tomography (SPECT) with ¹²³I-Ioflupane (DaTSCAN) have shown to detect even early stages of the disease. In this paper, we use the striatal binding ratio (SBR) values that are calculated from the ¹²³I-Ioflupane SPECT scans (as obtained from the Parkinson’s progression markers initiative (PPMI) database) for developing automatic classification and prediction/prognostic models for early PD. We used support vector machine (SVM) and logistic regression in the model building process. We observe that the SVM classifier with RBF kernel produced a high accuracy of more than 96% in classifying subjects into early PD and healthy normal; and the logistic model for estimating the risk of PD also produced high degree of fitting with statistical significance indicating its usefulness in PD risk estimation. Hence, we infer that such models have the potential to aid the clinicians in the PD diagnostic process.     

灰色—支持向量机的空调负荷预测

对空调负荷进行准确预测不仅对空调优化控制的意义重大,而且也是实现空调经济运行与节能的关键所在。为了提高建筑空调负荷的预测精度,在分析灰色模型和支持向量机建模特点基础上提出了一种空调负荷组合预测算法。该方法综合了灰色建模计算过程简单以及支持向量机自学习和泛化能力强的优点,能够更加有效地利用样本数据的有效信息,提高模型预测精度。首先,通过灰色建模过程弱化了样本数据的随机因素。然后,对灰色模型输出进行归一化处理及数据重构,以作为支持向量机的输入。最后,通过支持向量机模型的预测得到最终预测结果。将本文所提出的方法应用于福州一栋办公建筑的逐时空调负荷预测中,并与灰色模型及支持向量机模型作比较,证明了组合模型的预测值与实际运行值拟合度最高,平均绝对误差比灰色模型和支持向量机模型分别降低了47.84%和17.39%。该组合预测模型具有较高的预测精度和更好的泛化能力,具有较强的可行性和实用性。     

隐目标回归算法设计研究

对常用的回归方法进行研究.此类方法虽然几何解释明确、易于求解,但均须事先确定(或假定)变量间的因果关系,再考虑建模,在实际应用中,对于很难确定变量的因果关系的问题,如物联网数据分析,上述方法就会失效.为此,提出一种无需假定因变量的隐目标回归方法.该方法易于核化,可以推广到非线性回归问题.通过人工数据和国际标准数据集上的实验验证了所提算法的有效性.     

便携心电传感器的心房肥大诊断研究

基于便携式传感器的模式识别在心电(ECG)监护领域具有广泛的应用前景,并且在心律不齐、心肌梗塞、心室肥大等心电的识别算法上都已有大量的研究与应用,但在心房肥大诊断上却未有模式识别相关的研究成果。心房肥大病症的心电数据量不足给研究造成重大障碍,部分分类器无法适应小样本训练下的分类。针对小样本训练进行研究,对比了不同分类方法,显示了基于统计模式识别的支持向量机(SVM)应用于心房肥大的应用潜力。另外,由于不同个体的心房肥大心电存在差异,在实际应用环境中,SVM存在无法良好泛化的问题,存在类别错分的医学风险。针对类别错分情况,采用分类器融合的方法改进分类器,提出了在SVM分类器输出端增加了拒绝域的分类器(SVM-R)的方法。实验结果表明:SVMR有较高的分类准确率与诊断可信度。     

基于退化四元小波变换的纸币识别

针对如何提取纸币图像特征和提高识别率的问题,综合利用退化四元小波变换具有的相位特性,提出一种基于退化四元小波变换的纸币识别方法.该方法首先对采集的纸币图像进行倾斜校正和边缘检测,然后运用退化四元小波对纸币图像进行分解操作,并对分解系数进行统计分析,将每个分解子带系数的能量和标准差作为该纸币图像的特征向量,最后将支持向量机作为分类器对纸币图像进行识别.本文方法在资源约束的嵌入式清分系统上实现,实验结果表明采用本文提出的算法突破了传统纸币识别系统识别率很难再提高的瓶颈,同时能够满足清分系统的实时性要求.