Truncated O-Glycan-Bearing MUC16 Enhances Pancreatic Cancer Cells Aggressiveness via α4β1 Integrin Complexes and FAK Signaling

Elevated levels of Mucin-16 (MUC16) in conjunction with a high expression of truncated O-glycans is implicated in playing crucial roles in the malignancy of pancreatic ductal adenocarcinoma (PDAC). However, the mechanisms by which such aberrant glycoforms present on MUC16 itself promote an increased disease burden in PDAC are yet to be elucidated. This study demonstrates that the CRISPR/Cas9-mediated genetic deletion of MUC16 in PDAC cells decreases tumor cell migration. We found that MUC16 enhances tumor malignancy by activating the integrin-linked kinase and focal adhesion kinase (ILK/FAK)-signaling axis. These findings are especially noteworthy in truncated O-glycan (Tn and STn antigen)-expressing PDAC cells. Activation of these oncogenic-signaling pathways resulted in part from interactions between MUC16 and integrin complexes (α4β1), which showed a stronger association with aberrant glycoforms of MUC16. Using a monoclonal antibody to functionally hinder MUC16 significantly reduced the migratory cascades in our model. Together, these findings suggest that truncated O-glycan containing MUC16 exacerbates malignancy in PDAC by activating FAK signaling through specific interactions with α4 and β1 integrin complexes on cancer cell membranes. Targeting these aberrant glycoforms of MUC16 can aid in the development of a novel platform to study and treat metastatic pancreatic cancer.     

A Petri Net based approach to determine the disassembly strategy of a product

In order to protect the environment and regain value added to products, a process known as disassembly has come into the limelight. This process is to be applied to reuse abandoned goods and materials. Manufacturers are being forced to establish disassembly plants and to develop their products' designs so as to maintain the government's dictate to dispose off their products in an environmentally responsible manner. This research presents a cost-based heuristic analysis for a circuit board assembly. Various components of the product and their assembly relationships are represented by a Petri Net diagram. Firing the transitions of the disassembly Petri Net is integrated with cost-based indices to develop an effective disassembly strategy. The methodology discussed here simplifies the decisionmaking process involved in disassembly planning. A comprehensive disassembly process planning system is proposed here and is exemplified by a case study of circuit board assembly.     

Rapid growth of angle-confined large-domain graphene bicrystals

In the chemical vapor deposition growth of large-area graphene polycrystalline thin films,the coalescence of randomly oriented graphene domains results in a high density of uncertain grain boundaries (GBs).The structures and properties of various GBs are highly dependent on the misorientation angles between the graphene domains,which can significantly affect the performance of the graphene films and impede their industrial applications.Graphene bicrystals with a specific type of GB can be synthesized via the controllable growth of graphene domains with a predefined lattice orientation.Although the bicrystal has been widely investigated for traditional bulk materials,no successful synthesis strategy has been presented for growing two-dimensional graphene bicrystals.In this study, we demonstrate a simple approach for growing well-aligned large-domain graphene bicrystals with a confined tilt angle of 30° on a facilely recrystallized single-crystal Cu (100) substrate.Control of the density of the GBs with a misorientation angle of 30° was realized via the controllable rapid growth of subcentimeter graphene domains with the assistance of a cooperative catalytic surface-passivation treatment.The large-area production of graphene bicrystals consisting of the sole specific GBs with a tunable density provides a new material platform for fundamental studies and practical applications.     

Wave-induced flow of pore fluid in a cracked porous solid containing penny-shaped inclusions

An aim of current study is to analyze the contribution of reflected longitudinal waves to wave-induced fluid flow(WIFF)in the cracked porous solid.Initially,we ...     

Multiple Decision Expert Systems for Performance Analysis of a Boiler System

Artificial neural networks (ANN)-based multiple decision expert systems (MDES) were developed for assessing the performance of a boiler system. Different configurations of ANN were used with different decision combination methods, including a neural combiner, to propose the model. The model was developed using the plant data collected over a period of five months to predict steam temperature, pressure, and mass flow rate, using feed water pressure, feed water temperature, conveyor speed, and incinerator exit temperature as the input parameters. The predictive capability of the model is evaluated in terms of both correlation coefficient (R) and mean absolute percentage error (MAPE). The results observed from this work demonstrate that neural combiner and ANN-based MDES can efficiently predict the data on steam properties consistently, and that the model can serve as an efficient tool for monitoring boiler behavior under real-time conditions. Superiority of the proposed model over others under various scenarios is also demonstrated.     

Photoreceptor Cells Constitutively Express IL-35 and Promote Ocular Immune Privilege

Interleukin-27 is constitutively secreted by microglia in the retina or brain, and upregulation of IL-27 during neuroinflammation suppresses encephalomyelitis and autoimmune uveitis. However, while IL-35 is structurally and functionally similar to IL-27, the intrinsic roles of IL-35 in CNS tissues are unknown. Thus, we generated IL-35/YFP-knock-in reporter mice (p35-KI) and demonstrated that photoreceptor neurons constitutively secrete IL-35, which might protect the retina from persistent low-grade inflammation that can impair photoreceptor functions. Furthermore, the p35-KI mouse, which is hemizygous at the il12a locus, develops more severe uveitis because of reduced IL-35 expression. Interestingly, onset and exacerbation of uveitis in p35-KI mice caused by extravasation of proinflammatory Th1/Th17 lymphocytes into the retina were preceded by a dramatic decrease of IL-35, attributable to massive death of photoreceptor cells. Thus, while inflammation-induced death of photoreceptors and loss of protective effects of IL-35 exacerbated uveitis, our data also suggest that constitutive production of IL-35 in the retina might have housekeeping functions that promote sterilization immunity in the neuroretina and maintain ocular immune privilege.     

On self-healing digital system design

In recent years there has been a significant growth of interest in exploiting the principles of biological processes to create powerful methodologies for solving computational problems. This paper discusses how these features have been exploited in digital hardware design. It also introduces an architecture for implementing self-healing digital systems that is inspired by the antigen protection mechanism employed by the human immune system. In the proposed architecture, a spare cell is dedicated to replace one in a group of four functional cells. Once one of these four functional cells is found to be faulty, the spare cell is cloned as the faulty cell. This architecture is especially suitable for tolerating soft errors in functional cells or on interconnect lines. Another major advantage of this architecture is that the outputs of functional cells are connected to the inputs of other physically adjacent functional cells, thus making it appropriate for nanocomputing system design.