This paper presents a unified framework for distributed filtering and control of state-space processes. To this end, a distributed Kalman filtering algorithm is developed via decomposition of the ...optimal centralized Kalman filtering operations. This decomposition is orchestrated in a fashion so that each agent retains a Kalman style filtering operation and an estimate of the state vector. In this setting, the agents mirror the operations of the centralized Kalman filter in a distributed fashion through embedded average consensus fusion of local state vector estimates and their associated covariance information. For rigor, closed-form expressions for the mean and mean square error performance of the developed distributed Kalman filter are derived. More importantly, in contrast to current approaches, due to the comprehensive framework for fusion of the covariance information, a duality between the developed distributed Kalman filter and decentralized control is established. Thus, resulting in an effective and all inclusive distributed framework for filtering and control of state-space processes over a network of agents. The introduced theoretical concepts are validated using the simulations that indicate a precise match between simulation results and the theoretical analysis. In addition, simulations indicate that performance levels comparable to that of the optimal centralized approaches are attainable.
Full-duplex relaying is more spectrally efficient than half-duplex relaying as only one channel use is needed per two hops. However, it is crucial to minimize relay self-interference to render full ...duplex feasible. For this purpose, we analyze a broad range of multiple-input multiple-output (MIMO) mitigation schemes: natural isolation, time-domain cancellation, and spatial suppression. Cancellation subtracts replicated interference signal from the relay input while suppression reserves spatial dimensions for receive and transmit filtering. Spatial suppression can be achieved by antenna subset selection, null-space projection, i.e., receiving and transmitting in orthogonal subspaces, or joint transmit and receive beam selection to support more spatial streams by choosing the minimum eigenmodes for overlapping subspaces. In addition, minimum mean square error (MMSE) filtering can be employed to maintain the desired signal quality, which is inherent for cancellation, and the combination of time- and spatial-domain processing may be better than either alone. Targeting at minimal interference power, we solve optimal filters for each scheme in the cases of joint, separate and independent design. The performance of mitigation schemes is evaluated and compared by simulations. The results confirm that self-interference can be mitigated effectively also in the presence of imperfect side information.
The field of synthetic biology promises to revolutionize biotechnology through the design of organisms with novel phenotypes useful for medicine, agriculture and industry. However, a limiting factor ...is the ability of current methods to assemble complex DNA molecules encoding multiple genetic elements in various predefined arrangements. We present here a hierarchical modular cloning system that allows the creation at will and with high efficiency of any eukaryotic multigene construct, starting from libraries of defined and validated basic modules containing regulatory and coding sequences. This system is based on the ability of type IIS restriction enzymes to assemble multiple DNA fragments in a defined linear order. We constructed a 33 kb DNA molecule containing 11 transcription units made from 44 individual basic modules in only three successive cloning steps. This modular cloning (MoClo) system can be readily automated and will be extremely useful for applications such as gene stacking and metabolic engineering.
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Keratins are essential elements of the cytoskeleton of normal and malignant epithelial cells. Because carcinomas commonly maintain their specific keratin expression pattern during malignant ...transformation, keratins are extensively used as tumor markers in cancer diagnosis including the detection of circulating tumor cells in blood of carcinoma patients. Interestingly, recent biological insights demonstrate that epithelial keratins should not only be considered as mere tumor markers. Emerging evidence suggests an active biological role of keratins in tumor cell dissemination and metastasis. In this review, we illustrate the family of keratin proteins, summarize the latest biological insights into keratin function related to cancer metastasis and discuss the current use of keratins for detection of CTCs and other blood biomarkers used in oncology.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Clinical tumor dormancy is specified as an extended latency period between removal of the primary tumor and subsequent relapse in a cancer patient who has been clinically disease-free. In particular, ...patients with estrogen receptor-positive breast cancer can undergo extended periods of more than five years before they relapse with overt metastatic disease. Recent studies have shown that minimal residual disease in breast cancer patients can be monitored by different liquid biopsy approaches like analysis of circulating tumor cells or cell-free tumor DNA. Even though the biological principles underlying tumor dormancy in breast cancer patients remain largely unknown, clinical observations and experimental studies have identified emerging mechanisms that control the state of tumor dormancy. In this review, we illustrate the latest discoveries on different molecular aspects that contribute to the control of tumor dormancy and distant metastatic relapse, then discuss current treatments affecting minimal residual disease and dormant cancer cells, and finally highlight how novel liquid biopsy based diagnostic methodologies can be integrated into the detection and molecular characterization of minimal residual disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein primarily known to mediate homotypic cell contacts in epithelia tissues. Because EpCAM expression is limited to normal and ...malignant epithelia, it has been used as diagnostic marker for the detection of carcinoma cells in mesenchymal organs such as blood, bone marrow or lymph nodes. In particular, the detection and molecular characterization of EpCAM-positive circulating tumor cells (CTCs) in the blood of carcinoma patients has gained considerable interest over the past ten years. EpCAM is primarily considered as an adhesion molecule, but recent studies have shown diverse biological functions including regulation of cell proliferation and cancer stemness. In this review, we summarize the current knowledge on the biological properties of EpCAM with emphasis on mechanisms involved in cancer progression and discuss the clinical implications of these findings for the clinical use of EpCAM as a diagnostic marker.
Generation of customized DNA binding domains targeting unique sequences in complex genomes is crucial for many biotechnological applications. The recently described DNA binding domain of the ...transcription activator-like effectors (TALEs) from Xanthomonas consists of a series of repeats arranged in tandem, each repeat binding a nucleotide of the target sequence. We present here a strategy for engineering of TALE proteins with novel DNA binding specificities based on the 17.5 repeat-containing AvrBs3 TALE as a scaffold. For each of the 17 full repeats, four module types were generated, each with a distinct base preference. Using this set of 68 repeat modules, recognition domains for any 17 nucleotide DNA target sequence of choice can be constructed by assembling selected modules in a defined linear order. Assembly is performed in two successive one-pot cloning steps using the Golden Gate cloning method that allows seamless fusion of multiple DNA fragments. Applying this strategy, we assembled designer TALEs with new target specificities and tested their function in vivo.
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Abstract
Background
Brain metastasis (BM) in non-small-cell lung cancer (NSCLC) has a very poor prognosis. Recent studies have demonstrated the importance of cell adhesion molecules in tumor ...metastasis. The aim of our study was to investigate the role of activated leukocyte cell adhesion molecule (ALCAM) in BM formation in NSCLC.
Methods
Immunohistochemical analysis was performed on 143 NSCLC primary tumors and BM. A correlation between clinicopathological parameters and survival was developed. Biological properties of ALCAM were assessed in vitro by gene ablation using CRISPR/Cas9 technology in the NCI-H460 NSCLC cell line and in vivo by intracranial and intracardial cell injection of NCI-H460 cells in NMRI-Foxn1nu/nu mice.
Results
ALCAM expression was significantly upregulated in NSCLC brain metastasis (P = 0.023) with a de novo expression of ALCAM in 31.2% of BM. Moderate/strong ALCAM expression in both primary NSCLC and brain metastasis was associated with shortened survival. Functional analysis of an ALCAM knock-out (KO) cell line showed a significantly decreased cell adhesion capacity to human brain endothelial cells by 38% (P = 0.045). In vivo studies showed significantly lower tumor cell dissemination in mice injected with ALCAM-KO cells in both mouse models, and both the number and size of BM were significantly diminished in ALCAM depleted tumors.
Conclusions
Our findings suggest that elevated levels of ALCAM expression promote BM formation in NSCLC through increased tumor cell dissemination and interaction with the brain endothelial cells. Therefore, ALCAM could be targeted to reduce the occurrence of BM.
Key Points
1. ALCAM expression associates with poor prognosis and brain metastasis in NSCLC.
2. ALCAM mediates interaction of NSCLC tumor cells with brain vascular endothelium.
3. ALCAM might represent a novel preventive target to reduce the occurrence of BM in NSCLC.
Using the diffusion strategies, an unknown parameter vector can be estimated over an adaptive network by combining the intermediate estimates of neighboring nodes at each node. We propose an ...extension to the diffusion recursive least-squares algorithm by allowing partial sharing of the entries of the intermediate estimate vectors among the neighbors. Accordingly, the proposed algorithm, termed partial-diffusion recursive least-squares (PDRLS), enables a trade-off between estimation performance and communication cost. We analyze the performance of the PDRLS algorithm and prove its convergence in both mean and mean-square senses. We also derive a theoretical expression for its steady-state mean-square deviation. Simulation results substantiate the efficacy of the PDRLS algorithm and demonstrate a good match between theory and experiment.
Prostate cancer is a hormone-driven disease and its tumor cell growth highly relies on increased androgen receptor (AR) signaling. Therefore, targeted therapy directed against androgen synthesis or ...AR activation is broadly used and continually improved. However, a subset of patients eventually progresses to castration-resistant disease. To date, various mechanisms of resistance have been identified including the development of AR-independent aggressive variant prostate cancer based on neuroendocrine transdifferentiation (NED). Here, we review the highly complex processes contributing to NED. Genetic, epigenetic, transcriptional aberrations and posttranscriptional modifications are highlighted and the potential interplay of the different factors is discussed. Background Aggressive variant prostate cancer (AVPC) with traits of neuroendocrine differentiation emerges in a rising number of patients in recent years. Among others, advanced therapies targeting the androgen receptor axis have been considered causative for this development. Cell growth of AVPC often occurs completely independent of the androgen receptor signal transduction pathway and cells have mostly lost the typical cellular features of prostate adenocarcinoma. This complicates both diagnosis and treatment of this very aggressive disease. We believe that a deeper understanding of the complex molecular pathological mechanisms contributing to transdifferentiation will help to improve diagnostic procedures and develop effective treatment strategies. Indeed, in recent years, many scientists have made important contributions to unravel possible causes and mechanisms in the context of neuroendocrine transdifferentiation. However, the complexity of the diverse molecular pathways has not been captured completely, yet. This narrative review comprehensively highlights the individual steps of neuroendocrine transdifferentiation and makes an important contribution in bringing together the results found so far.
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