Stereolithography Cure Process Modeling Using Acrylate Resin

In this paper, a complex stereolithography (SL) cure process model is presented that incorporates transient thermal and chemical effects which influence final part shape and properties. The model incorporates photopolymerization, mass diffusion, and heat transfer. Material properties are characterized and a comprehensive kinetic model parameterized for a model compound system. SL process simulations are performed using finite element methods with the software package FEMLAB, and validated by the capability of predicting the fabricated part dimensions. A degree of cure (DOC) threshold model is proposed which can predict the cure line size within 15% error, comparing with 30% prediction error by the exposure threshold model currently used in SL. Furthermore, through the sensitivity analysis conducted by the process model presented here, the sensitive parameters are identified and the SL bath temperature, photointiator absorptivity and concentration are found to be the most sensitive factors that affect the SL fabrication results. The sensitive variables will be the focus of further research meant to improve SL process speed and resolution.Mechanical Engineerin

Multi-View Region Adaptive Multi-temporal DMM and RGB Action Recognition

Human action recognition remains an important yet challenging task. This work proposes a novel action recognition system. It uses a novel Multiple View Region Adaptive Multi-resolution in time Depth Motion Map (MV-RAMDMM) formulation combined with appearance information. Multiple stream 3D Convolutional Neural Networks (CNNs) are trained on the different views and time resolutions of the region adaptive Depth Motion Maps. Multiple views are synthesised to enhance the view invariance. The region adaptive weights, based on localised motion, accentuate and differentiate parts of actions possessing faster motion. Dedicated 3D CNN streams for multi-time resolution appearance information (RGB) are also included. These help to identify and differentiate between small object interactions. A pre-trained 3D-CNN is used here with fine-tuning for each stream along with multiple class Support Vector Machines (SVM)s. Average score fusion is used on the output. The developed approach is capable of recognising both human action and human-object interaction. Three public domain datasets including: MSR 3D Action,Northwestern UCLA multi-view actions and MSR 3D daily activity are used to evaluate the proposed solution. The experimental results demonstrate the robustness of this approach compared with state-of-the-art algorithms.Comment: 14 pages, 6 figures, 13 tables. Submitte

Single-channel kinetics of BK (Slo1) channels

Single-channel kinetics has proven a powerful tool to reveal information about the gating mechanisms that control the opening and closing of ion channels. This introductory review focuses on the gating of large conductance Ca2+- and voltage-activated K+ (BK or Slo1) channels at the single-channel level. It starts with single-channel current records and progresses to presentation and analysis of single-channel data and the development of gating mechanisms in terms of discrete state Markov (DSM) models). The DSM models are formulated in terms of the tetrameric modular structure of BK channels, consisting of a central transmembrane pore-gate domain (PGD) attached to four surrounding transmembrane voltage sensing domains (VSD) and a large intracellular cytosolic domain (CTD), also referred to as the gating ring. The modular structure and data analysis shows that the Ca2+ and voltage dependent gating considered separately can each be approximated by 10-state two-tiered models with 5 closed states on the upper tier and 5 open states on the lower tier. The modular structure and joint Ca2+ and voltage dependent gating are consistent with a 50 state two-tiered model with 25 closed states on the upper tier and 25 open states on the lower tier. Adding an additional tier of brief closed (flicker states) to the 10-state or 50-state models improved the description of the gating. For fixed experimental conditions a channel would gate in only a subset of the potential number of states. The detected number of states and the correlations between adjacent interval durations are consistent with the tiered models. The examined models can account for the single-channel kinetics and the bursting behavior of gating. Ca2+ and voltage activate BK channels by predominantly increasing the effective opening rate of the channel with a smaller decrease in the effective closing rate. Ca2+ and depolarization thus activate by mainly destabilizing the closed states

Low resistance, large dimension entrance to the inner cavity of BK channels determined by changing side-chain volume

Large-conductance Ca2+- and voltage-activated K+ (BK) channels have the largest conductance (250–300 pS) of all K+-selective channels. Yet, the contributions of the various parts of the ion conduction pathway to the conductance are not known. Here, we examine the contribution of the entrance to the inner cavity to the large conductance. Residues at E321/E324 on each of the four α subunits encircle the entrance to the inner cavity. To determine if 321/324 is accessible from the inner conduction pathway, we measured single-channel current amplitudes before and after exposure and wash of thiol reagents to the intracellular side of E321C and E324C channels. MPA− increased currents and MTSET+ decreased currents, with no difference between positions 321 and 324, indicating that side chains at 321/324 are accessible from the inner conduction pathway and have equivalent effects on conductance. For neutral amino acids, decreasing the size of the entrance to the inner cavity by substituting large side-chain amino acids at 321/324 decreased outward single-channel conductance, whereas increasing the size of the entrance with smaller side-chain substitutions had little effect. Reductions in outward conductance were negated by high [K+]i. Substitutions had little effect on inward conductance. Fitting plots of conductance versus side-chain volume with a model consisting of one variable and one fixed resistor in series indicated an effective diameter and length of the entrance to the inner cavity for wild-type channels of 17.7 and 5.6 Å, respectively, with the resistance of the entrance ∼7% of the total resistance of the conduction pathway. The estimated dimensions are consistent with the structure of MthK, an archaeal homologue to BK channels. Our observations suggest that BK channels have a low resistance, large entrance to the inner cavity, with the entrance being as large as necessary to not limit current, but not much larger

Residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacity.

Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs) have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC) to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs). We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell's ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell's ability to drive disease recurrence