Statistical Approach to Detection of Attacks for Stochastic Cyber-Physical Systems

We study the problem of detecting an attack on a stochastic cyber-physical system. We aim to treat the problem in its most general form. We start by introducing the notion of asymptotically detectable attacks, as those attacks introducing changes to the system's output statistics which persist asymptotically. We then provide a necessary and sufficient condition for asymptotic detectability. This condition preserves generality as it holds under no restrictive assumption on the system and attacking scheme. To show the importance of this condition, we apply it to detect certain attacking schemes which are undetectable using simple statistics. Our necessary and sufficient condition naturally leads to an algorithm which gives a confidence level for attack detection. We present simulation results to illustrate the performance of this algorithm

Flow Rate Independent Multiscale Liquid Biopsy for Precision Oncology

Immunoaffinity-based liquid biopsies of circulating tumour cells (CTCs) hold great promise for cancer management, but typically suffer from low throughput, relative complexity and post-processing limitations. Here we address these issues simultaneously by decoupling and independently optimising the nano-, micro- and macro-scales of a CTC enrichment device that is both simple to fabricate and operate. At its core is a scalable macroscale mesh with optimised micropores, nano-functionalised with antibodies against cell surface proteins. Unlike other affinity-based liquid biopsies, optimum capture can be achieved independently of the flow rate, as demonstrated with constant capture efficiencies, above 75%, between 50-200 uL/min. The device achieved 96% sensitivity and 100% specificity when used to detect CTCs in the blood of 79 cancer patients and 20 healthy controls. To demonstrate its post-processing capabilities, we used immunofluorescence labelling to identify PD-L1+ CTCs in 36% of patients (n=33) as potential responders to immune checkpoint inhibition therapy. Finally, our device achieved an 80% positive match in the identification of HER2+ breast cancer (n=26) compared to clinical standard FISH on solid biopsy. The results suggest that our approach, which overcomes major limitations previously associated with affinity-based liquid biopsies, could provide a versatile tool to improve cancer management.Comment: 21 pages, 5 figures (+ supplementary materials: 11 pages, 10 figures

Egg white-mediated green synthesis of silver nanoparticles with excellent biocompatibility and enhanced radiation effects on cancer cells

A simple, cost-effective, and environmentally friendly approach to the aqueous-phase synthesis of silver (Ag) nanoparticles was demonstrated using silver nitrate (AgNO3) and freshly extracted egg white. The bio-conjugates were characterized by UV-visible spectroscopy, transmission electron microscopy, Fourier transform infrared spectrometry, and dynamic light scattering. These results indicated that biomolecule-coated Ag nanoparticles are predominantly spherical in shape with an average size of 20 nm. The proteins of egg white, which have different functional groups, played important roles in reducing Ag+ and maintaining product attributes such as stability and dispersity. In vitro cytotoxicity assays showed that these Ag-protein bio-conjugates showed good biocompatibility with mouse fibroblast cell lines 3T3. Furthermore, X-ray irradiation tests on 231 tumor cells suggested that the biocompatible Ag-protein bio-conjugates enhanced the efficacy of irradiation, and thus may be promising candidates for use during cancer radiation therapy

Performance of Networked Control Systems

Data packet dropout is a special kind of time delay problem. In this paper, predictive controllers for networked control systems (NCSs) with dual-network are designed by model predictive control method. The contributions are as follows. (1) The predictive control problem of the dual-network is considered. (2) The predictive performance of the dual-network is evaluated. (3) Compared to the popular networked control systems, the optimal controller of the new NCSs with data packets dropout is designed, which can minimize infinite performance index at each sampling time and guarantee the closed-loop system stability. Finally, the simulation results show the feasibility and effectiveness of the controllers designed

Optimal estimation and control for lossy network: stability, convergence, and performance

In this paper, we study the problems of optimal estimation and control, i.e., the linear quadratic Gaussian (LQG) control, for systems with packet losses but without acknowledgment. Such acknowledgment is a signal sent by the actuator to inform the estimator of the incidence of control packet losses. For such system, which is usually called as a user datagram protocol (UDP)-like system, the optimal estimation is nonlinear and its calculation is time-consuming, making its corresponding optimal LQG problem complicated. We first propose two conditions: 1) the sensor has some computation abilities; and 2) the control command, exerted to the plant, is known to the sensor. For a UDP-like system satisfying these two conditions, we derive the optimal estimation. By constructing the finite and infinite product probability measure spaces for the estimation error covariances (EEC), we give the stability condition for the expected EEC, and show the existence of a measurable function to which the EEC converges in distribution, and propose some practical methods to evaluate the estimation performance. Finally, the LQG controllers are derived, and the conditions for the mean square stability of the closed-loop system are established

Flow rate-independent multiscale liquid biopsy for precision oncology

Immunoaffinity-based liquid biopsies of circulating tumor cells (CTCs) hold great promise for cancer management but typically suffer from low throughput, relative complexity, and postprocessing limitations. Here, we address these issues simultaneously by decoupling and independently optimizing the nano-, micro-, and macro-scales of an enrichment device that is simple to fabricate and operate. Unlike other affinity-based devices, our scalable mesh approach enables optimum capture conditions at any flow rate, as demonstrated with constant capture efficiencies, above 75% between 50 and 200 μL min–1. The device achieved 96% sensitivity and 100% specificity when used to detect CTCs in the blood of 79 cancer patients and 20 healthy controls. We demonstrate its postprocessing capacity with the identification of potential responders to immune checkpoint inhibition (ICI) therapy and the detection of HER2 positive breast cancer. The results compare well with other assays, including clinical standards. This suggests that our approach, which overcomes major limitations associated with affinity-based liquid biopsies, could help improve cancer management

The role of brevican in glioma: promoting tumor cell motility in vitro and in vivo

Background: Malignant glioma is a common primary tumor of the central nervous system. Brevican, an abundant extracellular matrix component in the adult brain, plays a critical role in the process of glioma. The mechanisms for the highly invasive behavior of gliomas are still poorly understood. The aim of this study was to examine whether brevican is a predictor of glioma and its roles in glioma cell motility. Methods: In this study, immunohistochemistry staining for brevican expression was performed in malignant gliomas and benign controls. We also explored the effects of brevican on cell adhesion and migration in brevican-overexpressed cells. Knockdown of brevican expression was achieved by stable transfection of U251 cells transduced with a construct encoding a short hairpin DNA directed against the brevican gene, which correspondingly, down-regulated the proliferation, invasion and spread of brevican-expressing cells. Moreover, the role of brevican in the growth and progression of glioma was demonstrated by in vivo studies. Results: Our results provide evidence for the molecular and cellular mechanisms that may underlie the motility-promoting role of brevican in the progression of glioma. The role of brevican as a target for immunotherapy might be taken into consideration in future studies. Conclusions: This study suggests that expression of brevican is associated with glioma cell adhesion, motility and tumor growth, and also is related to glioma cell differentiation, therefore it may be a marker for malignance degree of gliom

Diagnostic Significance of Serum IgG Galactosylation in CA19-9-Negative Pancreatic Carcinoma Patients

Background: Although Carbohydrate antigen 19-9 (CA19-9) is considered clinically useful and informative for pancreatic carcinoma (PC), false positive results, and false negative results have restricted its clinical use. Especially missed or delayed diagnosis of PC patients with negative CA19-9 value limited the utility. To improve prognosis of PC patients, the discovery of reliable biomarkers to assist CA19-9 is desired. Serum IgG galactosylation based on our previous report was altered in PC patients comparing to healthy controls. The objective of this study was to explore the diagnostic significance of IgG galactosylation in assisting CA19-9 for PC in a comprehensive way.Methods: Serum IgG galactosylation profiles were analyzed by MALDI-MS in cohort 1 (n = 252) and cohort 2 in which all CA19-9 levels were negative (n = 133). In each cohort, not only healthy controls and PC patients but also benign pancreatic disease (BPD) patients were enrolled. Peaks were acquired by the software of MALDI-MS sample acquisition, followed by being processed and analyzed by the software of Progenesis MALDI. IgG Gal-ratio, which was calculated from the relative intensity of peaks G0, G1, and G2 according to the formula (G0/(G1+G2×2)), was employed as an index for indicating the distribution of IgG galactosylation.Results: The Gal-ratio was elevated in PC comparing with that in non-cancer group (healthy controls and BPD). The area under the receiver operating characteristic curve (AUC) of IgG Gal-ratio was higher than that of CA19-9 (0.912 vs. 0.814). The performance was further improved when Gal-ratio and CA19-9 were combined (AUC: 0.928). Meanwhile, Gal-ratio also had great diagnostic value with a sensitivity of 92.31% (AUC: 0.883) in detection of PC at early stage. Notably, IgG Gal-ratio has great sensitivity (90.63%) and specificity (76.81%) in CA19-9-negative PC patients.Conclusions: IgG Gal-ratio had a great performance in detection of PC and could be used to assist CA19-9 in improving diagnosis performance through early stage detection, differentiation from BPD, and PC diagnosis with CA19-9-negative level